Exhibit No. 10.11
CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE OMISSIONS.
PROFESSIONAL SERVICE AGREEMENT
This Professional Service Agreement (this "Agreement") is made and entered into
as of the 9th day of May, 2001, by and between MIMC, INC., having a place of
business located at 0000 Xxxxxxxxx Xxxx, Xxxxx 000, Xxxxxxxxx, XX 00000 ("MIMC")
and NitroMed, Inc., having a place of business located at 00 Xxx Xxxx Xxxxx,
Xxxxxxx, XX 00000 (the "Sponsor").
RECITALS
A. MIMC is engaged in the business of providing administrative and technical
assistance to the pharmaceutical and medical device industry with respect to the
preparation and implementation of clinical plans and the management of clinical
trials.
B. The Sponsor is a pharmaceutical company which desires to engage the services
of MIMC to manage a clinical trial which will be conducted pursuant to and in
accordance with the Protocol: "Multi-center Confirmatory Trial BiDil(R) in the
Treatment of Heart Failure". MIMC will provide such services to the Sponsor oN
the terms and conditions set forth herein.
NOW, THEREFORE, in consideration of the premises and the mutual agreements
herein contained, the parties hereto agree as follows:
ARTICLE I
DEFINITIONS
When used in this Agreement, the following terms shall have the following
meanings:
1.1 "Adverse Event" shall mean any adverse, noxious or pathological change as
compared to pre-existing conditions that occurs during a clinical trial, whether
considered drug/placebo-related or not. This includes trial phases without
medication, such as run-in, wash-out or follow-up.
1.2 "Agreement" shall have the meaning set forth in the preamble.
1.3 "CRF" shall mean the case report form which is completed for each patient
enrolled in the Study.
1.4 "Ethics Committee" shall have the meaning set forth in Section 2.3(a)(ii).
1.5 "Event of Default" shall have the meaning set forth in Section 6.1.
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1.6 "Investigator" shall mean a clinician or physician who has entered into a
contract via MIMC for the purpose of enrolling patients into the Study and
executing the Protocol of the Sponsor.
1.7 "Investigator Site" shall mean an Investigator's office, clinical facility
or other site at which the Study is to be conducted.
1.8 "MIMC" shall have the meaning set forth in the preamble.
1.9 "Monitor" shall mean an employee of MIMC or agent under contract to MIMC who
serves as a clinical monitor at a particular Investigator Site during the Study.
1.10 "Non-Completed Patient" shall mean any patient who does not complete the
study for any reason.
1.11 "Person" shall mean any individual, corporation, proprietorship, firm,
partnership, trust, association or other entity.
1.12 "Protocol" shall have the meaning set forth in Recital B.
1.13 "Serious Adverse Event" shall mean death, or an immediate life-threatening,
permanently disabling event or an event which requires prolonged
hospitalization, or an event which causes a congenital anomaly or cancer, or an
intentional or accidental overdose.
1.14 "Sponsor" shall have the meaning set forth in the preamble.
1.15 "Sponsor Product" shall mean the product supplied by the Sponsor for use in
the Study.
1.16 "Study" shall have the meaning set forth in Section 2.2.
ARTICLE II
DUTIES OF MIMC
2.1 Consulting Services. To the extent mutually agreed by MIMC and the Sponsor,
MIMC shall provide consulting services to the Sponsor with respect to such
matters as clinical study design, preparation and review of the Protocol and
CRF, and selection of Investigators.
2.2 Clinical Trials Management Services.
The Sponsor hereby retains MIMC to provide the services as enumerated in
Sections 2.3 through Section 2.5 and as defined in Exhibit A of this Agreement
with respect to a research clinical study (the "Study") to be conducted pursuant
to and in strict accordance with the terms of the Protocol. MIMC will conduct
the study in accordance with the convention of Helsinki, and the FDA and EC,
Good Clinical Practices (GCP) requirements, as well as in accordance with the
individual national regulations in the countries where the Study will take
place.
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2.3 Selection of Investigators and Other Experts.
(a) At the request of, and subject to the approval of the Sponsor, MIMC will
undertake the selection of [**] qualified experts in the field of Cardiology to
serve as Investigators with respect to the Study. To the extent desired by the
Sponsor, MIMC will enter into negotiations directly with such Investigators on
behalf of the Sponsor with respect to such matters as compensation, liability,
and other material terms of the contract between the Sponsor and the
Investigator. Any such contract which is negotiated by MIMC on behalf of the
Sponsor will be subject to approval by the Sponsor. The Sponsor agrees that
prior to the beginning of the Study, the Sponsor will provide individual written
indemnification to each Investigator and a copy to MIMC.
(b) MIMC will ensure that all Investigators and their respective Investigator
Sites have the facilities and capabilities necessary to conduct the study in
strict accordance with the Protocol.
(c) MIMC will obtain a written commitment from the Investigators to ensure that
(1) the Investigator participating in the Study and his study nurse and/or
coordinator have reviewed the Protocol and understand their obligations
thereunder and (2) an Ethics Committee with jurisdiction over the Investigator
and the Investigator Site (the "Ethics Committee") will be responsible for the
initial and continuing (at least once during the Study) review and approval of
the Study and of any patient recruitment advertising.
(d) MIMC will ensure that each Investigator does not initiate the Study until
the Sponsor (a) has received each of the following: (1) country-specific
documentation and curricula vitae for the Investigator and Investigator's staff;
(2) written proof that the Ethics Committee has reviewed and approved the Study
and the informed consent; (3) written confirmation of any advertising to be used
for patient recruitment; and (4) written confirmation that any and all other
requirements of Sponsor have been and will be met; and (b) has given written
authorization to initiate the study.
(e) MIMC will ensure that the Study is conducted in strict accordance with the
Protocol, the condition of Helsinki, the FDA and EC, and GCP requirements, and
the conditions specified in the Investigator's foreign country requirements (if
applicable), regulations or standards and the conditions imposed by the
Investigator Site and the Ethics Committee.
(f) MIMC will ensure that Investigator makes no changes in the Protocol or the
Study without prior written approval of MIMC and the Sponsor, except when
necessary to eliminate an apparent immediate health hazard to a participating
patient and, in those cases, MIMC will ensure that the Investigator notifies
MIMC, the Sponsor and the Ethics Committee immediately.
(g) MIMC will ensure that Investigator reports promptly to MIMC, Sponsor and to
the Ethics Committee: all changes in the Study as authorized by subsection (f)
above; and all unanticipated problems involving risks to participating patients
or others.
(h) MIMC will ensure that the Investigator initiates patient enrollment upon
dates established by the Sponsor and that each patient has executed and
delivered an informed consent acceptable to the Sponsor and the Ethics
Committee.
(i) MIMC will ensure that each Investigator shall use his best efforts to
complete a minimum of [**] qualified patients within an [**] period from
commencement of Study for a collective guaranteed completion of [**] patients.
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(j) MIMC will ensure that treatment of all patients enrolled will be completed
and ensure that verified CRFs and a final report on the Study will be returned
to the Sponsor no later than [**] from the date of Study completion.
(k) MIMC will ensure that the Investigator and Investigator Site keep complete
and accurate records, including original patient, laboratory and drug inventory
records, of the conduct, status, progress and results of the Study in such form
as may be reasonably requested by the Sponsor and that access to and copies of
such records will be made available to MIMC and the Sponsor at all reasonable
times. MIMC will ensure that such records will not be destroyed without the
Sponsor's prior written consent and an opportunity for the Sponsor to take
possession of such records.
2.4 Clinical Monitoring.
(a) MIMC will assign a qualified Monitor to each Investigator Site. At the
initiation visit, the Monitor will determine whether such site is fully equipped
with the correct supply of investigational drugs, CRFs and other medical
supplies and all forms necessary for proper implementation of the Protocol. At
such time, the Monitor will discuss the Protocol with the Investigator, any
on-site coordinator, and other members of Investigator's staff; will collect all
necessary documentation for implementation of the study; and will provide such
persons with a detailed outline of the procedures to be followed in executing
the Protocol and conducting the Study. The Sponsor may choose to attend any such
initiation visit as long as notice of such intent is provided to MIMC within one
(1) week prior to the scheduled visit.
(b) During the Study, all case report forms will be faxed to the offices of
MIMC. In addition, the Monitor will visit the Investigator Site approximately
[**] times per the requirements of the Protocol. The first of these site visits
will occur after one to two (1 -2 ) patients have been enrolled in the Study and
subsequently at study closeout. The final close-out visit will occur no later
than [**] after the last patient has completed all Study requirements. During
such visits, the Monitor will be responsible for reviewing each patient's CRF
and other source documentation in order to determine:
(i) continued acceptability of the Investigator Site as Study center;
(ii) adherence to the Protocol;
(iii) adherence to the current laws, rules and regulations regarding obligations
to each patient and conduct of investigational studies;
(iv) maintenance of adequate records with respect to patient identification,
signed informed consents, clinical observations, drug receipt and disposition
and any other records required to be maintained by the Protocol or laws, rules
or regulations; and
(v) reports submitted by each Investigator relating to the Study are timely,
adequate and accurate.
(c) The Sponsor, having given reasonable notice, may join with MIMC on its
monitoring visit as deemed necessary. At any time during the conduct of the
Study, however, the Sponsor, its agents and consultants, and representatives of
applicable country regulatory agencies shall be
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permitted to inspect the Investigator Site, all pertinent patient records, and
all other pertinent information pertaining to the Study.
(d) After consultation with the Sponsor, MIMC shall withdraw the Study from the
Investigator if such site does not comply with each of the obligations described
in Section 2.3 above or meet the standards described in the Section 2.4.
Patients recruited by that Investigator or Investigator Site who are
disqualified for inclusion in the Study, for whatever reason, will be replaced
after MIMC obtains approval from the Sponsor.
(e) MIMC shall review all CRFs from the Investigator Site for completeness of
information, illegible entries, missing data involving omission of specific
individual data elements and missing patient reports and promptly cause any such
inaccuracies, errors or omissions to be corrected by the Investigator Site.
(f) MIMC shall perform on-site drug accountability and reconciliation as part of
the monitoring visits.
(g) MIMC shall review the source documents in conjunction with all CRFs for [**]
percent ([**]%) of the patients at the Investigator Site to insure that
inclusion/exclusion criteria are met at the initial visit. In addition, for [**]
percent ([**]%) of the patients enrolled, the source documents will be compared
to the CRFs at subsequent visits. This comparison will check for completeness of
information, illegible entries, missing data involving omission of specific
individual data elements, missing patient reports, inconsistencies between
documents, and adequacy of source documents. MIMC will promptly cause any such
inaccuracies, errors or omissions to be corrected by the Investigator.
(h) MIMC shall submit monthly progress reports to the Sponsor regarding the
Study including the number of patients screened, enrolled, completed, as well as
drop-outs. Other management reports will be designated by the Sponsor.
(i) MIMC shall ensure that the Investigator returns all unused supplies of
Sponsor Product and other drugs to the Sponsor promptly upon completion or
termination of their participation in the Study, together with appropriate
information concerning the Study and CRFs and drug disposition.
(j) MIMC shall comply with, and require the Investigator to comply with, all
applicable laws and regulations and all rules and procedures of the Ethics
Committee and Investigator Site and to cooperate with, and cause the
Investigator to cooperate with, all regulatory agencies, the Ethics Committee,
the Investigator Site and the Sponsor.
(k) MIMC shall ensure that any Adverse Events have been properly reported during
the Study (see Article IV, Section 4.2 which describes one such reporting
requirement).
2.5 Data Collection and Reporting.
(a) All patient CRFs will be returned to MIMC on an ongoing basis. Once received
at MIMC, each CRF will be reviewed for completeness of information, illegible
entries, missing data involving omission of specific individual data elements
and missing patient reports.
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(b) MIMC will contact the Monitor via telephone and/or facsimile transmission
and will provide a list of all CRFs that are ambiguous or otherwise contain
apparent inaccuracies, errors or omissions by the Investigator.
(c) MIMC will review all matters noted in paragraph 2.4(b) with the Monitor to
ensure that all CRFs are completed accurately.
(d) Monitoring reports will be submitted to the Sponsor containing all
information as required by FDA or EC GCPs. MIMC will collect all required
information directly on forms generated by MIMC including: Study Initiation
(Pre-Study Visit Report), Interim Site Visit Report including Clinical Research
Report, Study Completion Site Report, Delayed Site Visit Report, Telephone
Communications, Unused Drug Supply, Investigator Final Report and Adverse Event
Worksheet. In addition bi-monthly enrollment status reports will be submitted to
the Sponsor including patient enrollment, patient drop-out and completion.
(e) All CRFs for completed visits will be returned to MIMC as soon as the
Monitor has completed the formal review. All CRFs will be catalogued and sent to
Sponsor in a timely fashion within two weeks of a site visit along with a Site
Visit Report, Significant Event Report, and a Status Report.
ARTICLE III
COMPENSATION OF MIMC
3.1 In consideration of MIMC's timely performance of its obligations hereunder,
the Sponsor will pay MIMC for work performed as set forth in Exhibit B.
3.2 In order that the Sponsor may comply with applicable federal tax laws and
regulations, MIMC agrees that if requested by the Sponsor, MIMC will report to
the Sponsor within sixty (60) days after the close of each calendar year the
dollar amount of the budget funds which MIMC and/or its Investigator expended on
research activities during the year. In order to assist MIMC in completing this
statement, the Sponsor will endeavor to provide MIMC with a summary of payments
made to it during such a year for this and other studies or research activity
conducted by it during the year.
3.3 MIMC will agree to negotiate on behalf of the Sponsor for all services
rendered by a central laboratory. MIMC will, at the request of the Sponsor,
manage all payment transactions on behalf of the Sponsor.
3.4 The Sponsor recognizes its liability to pay for any additional treatment
which may be necessary for a patient enrolled in this Study suffering from an
Adverse Event related to the Study and not related to a Protocol violation and
to the extent that the patient is not otherwise reimbursed by medical insurance.
Any payment of such medical expenses shall be a matter for the Sponsor to handle
provided prior approval is given by the Sponsor for said medical expenses.
3.5 The Sponsor may upon thirty (30) days written notice cancel this Agreement.
At such time of termination and upon submission of documentation, MIMC shall be
entitled to receive payment for all work actually performed, for out-of-pocket
expenses actually incurred and for
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non-cancelable commitments actually entered into on behalf of the Sponsor. In
addition, the Sponsor will pay a cancellation fee to MIMC of [**] percent
([**]%) of the balance of the fixed contract fees.
ARTICLE IV
OPERATING PROCEDURES AND ADVERSE EVENT REPORTING
4.1. Standard Operating Procedures. MIMC shall, at all times during the term of
this Agreement, use its best efforts in fulfilling its obligations hereunder and
conduct its business in accordance with the Sponsor's standard operating
procedures applicable to a business engaged in the management of clinical
studies similar to the Study. MIMC shall instruct each of its employees who are
involved with the Study as to compliance with such standard operating
procedures. The Sponsor shall be entitled to request and obtain a quality
assurance audit of MIMC's operations and procedures either prior to the
commencement of the Study or upon the conclusion thereof. MIMC shall cooperate
fully in any such audit. MIMC will also conduct, as part of their Standard
Operating Procedures, a quality assurance audit of each Investigator Site at the
conclusion of the Study.
4.2 Adverse Event Reporting. In the event that, during the course of performing
clinical monitoring services hereunder, MIMC shall become aware of the
occurrence of a Serious or other Adverse Event, MIMC shall notify the Sponsor of
such occurrence within twenty-four (24) hours thereafter. If such notification
is initially given by telephone, MIMC shall provide a written confirmation
thereof to the Sponsor within one (1) day following such oral notification. The
Sponsor shall have sole and complete responsibility for reporting the occurrence
of any such Adverse Event to the appropriate regulatory agency, and MIMC shall
have no liability whatsoever to any Person for failure to inform said agency of
such occurrence.
(a) MIMC will enter into an agreement with the Investigator in which the
Investigator will agree promptly to notify MIMC, who in turn will notify the
Sponsor, within twenty-four (24) hours of the occurrence of any Serious or other
Adverse Event, including any findings associated with the use of the Sponsor
Product that may suggest significant hazards, contraindications, side effects or
precautions pertinent to the safety of the Sponsor Product as a drug. Serious
Adverse Events will be reported by the Investigator to MIMC and by MIMC to
Sponsor immediately.
(b) MIMC agrees to cooperate fully with the Sponsor in promptly investigating
any Serious Adverse Event reported by an Investigator so that the Sponsor may
fulfill its regulatory obligations.
(c) MIMC will enter into an agreement with the Investigator in which the
Investigator will agree to advise MIMC or the Sponsor when the Investigator
feels that there is a need to provide reasonable and customary care to any
patient involved in the clinical study who exhibits symptomatology of an Adverse
Event.
4.3 Authority to Suspend or Cancel. Sponsor shall have the right and power,
exercisable in its sole discretion, to suspend or cancel the Study at any time,
and MIMC shall cooperate fully and immediately with the Sponsor to effectuate
such suspension or cancellation.
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ARTICLE V
CONFIDENTIALITY
5.1 Confidential Information. During the term of this Agreement and at all times
thereafter, MIMC shall not, directly or indirectly, disclose to any Person, or
use or otherwise exploit for MIMC's own benefit or for the benefit of any Person
other than the Sponsor, any confidential or proprietary information provided or
disclosed to MIMC which concerns the Sponsor or its Products (including, without
limitation, its business, operations, finances, products, ideas and plans), the
Study or the Protocol. MIMC agrees to commit each Investigator, Investigator
Site and all other Persons with access to confidential or proprietary
information to the same limits of confidentiality as outlined herein.
5.2 Limits on Confidentiality. Notwithstanding anything to the contrary
contained in Section 5.1, MIMC shall have no obligation hereunder to keep
confidential any information that (i) is in the public domain at the time it is
first disclosed to or acquired by MIMC, (ii) enters the public domain through no
fault of MIMC, (iii) is obtained by MIMC from a third Person who is lawfully in
possession thereof and not subject directly or indirectly to a contractual or
fiduciary relationship to the Sponsor (or any of its affiliates), or (iv) is
otherwise required by law to be disclosed. In the event disclosure of such
confidential or proprietary information is required by law, MIMC shall provide
the Sponsor with prompt notice of such requirement so that the Sponsor may seek
an appropriate protective order, and MIMC shall otherwise take reasonable
actions and cooperate with the Sponsor to avoid or minimize such disclosure. At
the request of the Sponsor, MIMC agrees to deliver to the Sponsor, at any time
during the term of this Agreement or thereafter, any confidential or proprietary
information in its possession or control.
5.3 Publications. Sponsor agrees that, after the data from the entire Study
becomes available, an Investigator may publish or communicate scientific data
arising from the conduct of this study provided that the manuscript or
presentation is sent to the Sponsor sixty (60) days prior to submission for
publication. The Sponsor shall have the right to remove any confidential or
proprietary information contained therein and to reasonably delay such
publication in order to file any patent application deemed appropriate by the
Sponsor.
5.4 Publicity. Neither party will use the other party's name or the name of any
of such other party's personnel in any publicity relating to this Agreement, the
Study or the Sponsor's Product without the prior written consent of such other
party, which consent shall not be unreasonably withheld.
ARTICLE VI
DEFAULT AND REMEDIES
6.1 Events of Default. The occurrence of any of the following events shall
constitute an event of default under this Agreement (an "Event of Default"):
(a) The Sponsor shall fail to pay when due any fee, charge or expense required
to be paid by it pursuant to Article III of this Agreement; or
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(b) The Sponsor or MIMC shall default in the due performance and observance of
any of their respective obligations hereunder, and such default shall continue
unremedied for a period of thirty (30) days after notice thereof shall have been
given to such party by the other party hereto, unless the defaulting party shall
have during such thirty (30) day period, provided, however, that no notice or
opportunity to cure shall be required in the event such default is a threat to
the health or safety of any Person; or
(c) The Sponsor or MIMC shall
(i) become insolvent or generally fail to pay, or admit in writing its inability
or unwillingness to pay, debts as they become due;
(ii) apply for, consent to, acquiesce in, permit, or suffer to exist the
appointment of a trustee, receiver, sequestrator or other custodian for itself
or its property, and such trustee, receiver, sequestrator or other custodian
shall not be discharged within sixty (60) days;
(iii) make a general assignment for the benefit of creditors; or
(iv) permit or suffer to exist the commencement of any bankruptcy,
reorganization, debt arrangement or other case or proceeding under any
bankruptcy or insolvency law, or any dissolution, winding up or liquidation
proceeding, and such case or proceeding, if commenced against a party, shall not
be stayed or dismissed within sixty (60) days.
6.2 Remedy Upon Default. Upon the occurrence of an Event of Default, the other
party to this Agreement may, at its option, terminate this Agreement at any time
thereafter by written notice to the defaulting party. The remedy specifically
provided for by this Section 6.2 shall not be exclusive and shall be in addition
to any other remedies which a party may have at law or in equity.
ARTICLE VII
INDEMNIFICATION
7.1 Indemnification by MIMC.
MIMC shall indemnify the Sponsor, its agents, servants and employees against,
and hold the Sponsor, its agents, servants and employees harmless from, any and
all losses, claims, actions, proceedings, costs, damages (excluding special or
consequential damages), and liabilities, including reasonable attorneys' fees,
arising out of, connected with or resulting from negligent or willful act or
omission on the part of MIMC or any Monitor or their respective agents, servants
or employees of erroneous data or reports or the breach by MIMC of any of its
obligations under this Agreement including, without limitation, the obligations
imposed by Article V hereof; provided that the Sponsor gives MIMC written notice
of any such loss, claim, etc. promptly after obtaining knowledge thereof. To the
extent requested by MIMC, the Sponsor shall cooperate fully with MIMC in the
defense of any such claim, action, etc. MIMC shall have the sole authority to
defend and/or settle any such loss, claim, etc. MIMC, in the defense of any such
loss, claim, etc. shall not, except with the consent of Sponsor, consent to
entry of any judgment or enter into any settlement which does not include as an
unconditional term thereof the giving
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by the claimant or plaintiff to Sponsor of a release from all liability in
respect of such loss, claim, etc., and MIMC shall not consent to entry of any
judgment or settle such loss, claim, etc. without the prior written consent of
Sponsor.
7.2 Indemnification by the Sponsor.
The Sponsor shall indemnify MIMC, its agents, servants and employees against,
and hold MIMC, its agents, servants and employees harmless from, any and all
losses, claims, actions, proceedings, costs, damages (excluding special or
consequential damages), and liabilities, including reasonable attorneys' fees,
arising out of, connected with or resulting from the negligent or willful act or
omission on the part of the Sponsor or the Investigator or their respective
agents, servants and employees (other than MIMC or the Monitor) in executing the
Protocol or conducting the Study or the breach by the Sponsor of any of its
obligations under this Agreement; provided that MIMC gives the Sponsor written
notice of any such loss, claim, etc. promptly after obtaining knowledge thereof.
To the extent requested by the Sponsor, MIMC shall cooperate fully with the
Sponsor in the defense of any such claim, action, etc. Sponsor shall have the
sole authority to defend and/or settle any such loss, claim, etc. Sponsor, in
the defense of any such loss, claim, etc., shall not, except with the consent of
MIMC, consent to entry of any judgment or enter into any settlement which does
not include as an unconditional term thereof the giving by the claimant or
plaintiff to MIMC of a release from all liability in respect of such loss,
claim, etc., and Sponsor shall not consent to entry of any judgment or settle
such loss, claim, etc. without the prior written consent of MIMC.
ARTICLE VIII
OWNERSHIP AND INTELLECTUAL PROPERTY RIGHTS
8.1 Ownership. MIMC acknowledges that the Sponsor is and at all times shall
remain the sole owner of the Sponsor Product. The Sponsor shall at all times
remain the sole owner of the CRFs and all reports on the Study submitted by the
Investigator, the Monitor or MIMC.
8.2 Developments. MIMC hereby assigns to the Sponsor all of MIMC's right, title,
and interest in and to all inventions, discoveries, improvements, methods,
developments, and works of authorship, whether or not patentable or
copyrightable, and all related intellectual property rights, which are created,
made, conceived, or reduced to practice by MIMC, or its agents, servants, or
employees, during the course of the performance of the Study or otherwise in the
course of the performance of MIMC's obligations hereunder. MIMC agrees to commit
each Investigator, Investigator Site and all other Persons engaged in the Study
or the provision of services in accordance with this Agreement to the same
obligation of assignment of developments as set forth above in this Section 8.2.
ARTICLE IX
MISCELLANEOUS PROVISIONS
9.1 Term of Agreement. The term of this Agreement shall be for a period
commencing on the date hereof and ending on December 31, 2002, but not before
receipt of all written reports, unless sooner terminated in accordance with
Article VI hereof or by the mutual agreement of
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MIMC and the Sponsor. Upon expiration of the term set forth above, this
Agreement may be extended or renewed as agreed upon by MIMC and the Sponsor.
9.2 Waivers, Amendments, Etc. The provisions of this Agreement may be amended,
modified or waived, from time to time, if such amendment, modification or waiver
is in writing and consented to by MIMC and the Sponsor. No delay or failure on
the part of either party in exercising any rights hereunder, and no partial or
single exercise thereof, shall constitute a waiver of such rights or of any
other rights hereunder.
9.3 Notices. All notices and other communications provided for herein shall be
in writing and addressed, delivered or transmitted to a party at its respective
address, or facsimile number set forth below or at such other address, or
facsimile number as may be designated by such party in a notice to the other
party. Any notice, if mailed and properly addressed with postage prepaid or if
properly addressed and sent by pre-paid courier service, shall be deemed given
when received; any notice, if transmitted by facsimile, shall be deemed given
when transmitted. Unless otherwise provided by a party, such notices shall be
addressed as follows:
If to MIMC:
Xxxxx X. Xxxxxxx
Executive Director of Administration
0000 Xxxxxxxxx Xxxx
Xxxxx 000
Xxxxxxxxx, XX 00000
Telephone: (000) 000-0000
Facsimile: (000) 000-0000
If to the Sponsor:
Xxxxxx Xxxxx
Chief Financial Officer
Nitromed, Inc.
00 Xxx Xxxx Xxxxx
Xxxxxxx, XX 00000
Telephone: (000) 000-0000
Facsimile: (000) 000-0000
9.4 Successors and Assigns. This Agreement shall be binding upon and shall inure
to the benefit of the parties hereto and their respective successors and
assigns; provided, however, that neither party may assign or transfer its rights
or obligations hereunder without the prior written consent of the other party,
except that Sponsor may assign this Agreement in connection with any merger,
consolidation, sale or transfer of all or substantially all of the assets of the
Sponsor, or sale or transfer of substantially all of Sponsor's rights relating
to the Sponsor Product and/or its use for the indications contemplated by the
Protocol.
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9.5 Severability. Any provision of this Agreement which is prohibited or
unenforceable in any jurisdiction shall, as to such provision and such
jurisdiction, be ineffective to the extent of such prohibition or
unenforceability without invalidating the remaining provisions of this Agreement
or affecting the validity or unenforceability of such provision in any other
jurisdiction.
9.6 Survival. The obligations of MIMC under Articles V and VIII and the
obligations of both parties under Article VII and any other provision which by
its terms is intended to survive shall survive the expiration or termination of
this Agreement.
9.7 Governing Law; Entire Agreement. This Agreement shall be governed by and
construed in accordance with the internal laws of the State of Maryland. This
Agreement and all exhibits and schedules hereto constitute the entire
understanding among the parties hereto with respect to the subject matter hereof
and supersede any prior agreements, written or oral, with respect thereto.
9.8 Relationship of the Parties. MIMC is solely an independent contractor, and
nothing in this Agreement shall be construed or interpreted as creating a
partnership, joint venture or any other similar relationship between MIMC and
the Sponsor. All persons employed by MIMC to serve as a Monitor with respect to
the Study or otherwise to carry out the duties of MIMC hereunder shall be and
remain at all times the employees of MIMC.
9.9 Headings. The various headings contained in this Agreement have been
inserted for convenience only and shall not affect the meaning or interpretation
of this Agreement or any provision hereof.
9.10 Force Majeure. Neither MIMC nor the Sponsor shall be responsible to the
other for failure to perform any of the obligations imposed by this Agreement,
provided such failure shall be occasioned by fire, flood, explosion, lightning,
windstorm, earthquake, subsidence of soil, failure or destruction, in whole or
in part, or machinery or equipment, failure of supply of materials,
discontinuity in the supply or power, governmental interference, civil
commotion, riot, war, strikes, labor disturbance, transportation difficulties,
labor shortage or cause beyond its reasonable control.
9.11 Debarment Certification. Neither MIMC nor any person employed thereby has
been debarred under Section #305(a) or (b) of the Federal Food, Drug and
Cosmetic Act and no debarred person will be in the future employed by MIMC in
connection with any work to be performed for or on behalf of Sponsor which may
later become part of any application for approval of a drug or biologic by the
FDA. If, at any time after execution of this contract, MIMC becomes aware that
MIMC or any person employed thereby is, or is in the process of being debarred,
MIMC hereby certifies that MIMC will so notify Sponsor at once.
12
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be executed
by their respective officers thereunto duly authorized as of the day and the
year first above written.
MIMC, Inc.
By: /s/ Xxxxx X. Xxxxxxx
------------------------------------
Xxxxx X. Xxxxxxx
Executive Director of Administration
Nitromed, Inc.
By: /s/ Xxxxxx Xxxxxx
-------------------------------
President
13
EXHIBIT A
Proposal for Clinical Trial Management Services
In Support of
Multi-center Confirmatory Trial
BiDil(R) in the Treatment of Heart Failure
Prepared for:
NitroMed, Inc
00 Xxx Xxxx Xxxxx
Xxxxxxx, Xxxxxxxxxxxxx 00000
Phone: 000-000-0000
FAX: 000-000-0000
Prepared by:
MIMC, Inc.
0000 Xxxxxxxxx Xxxx
Xxxxx 000
Xxxxxxxxx, XX 00000
Phone: 000-000-0000
Fax: 000-000-0000
January 18, 2001
SUMMARY
NITROMED, INC (NITROMED) is planning to perform a study of a product for the
oral treatment of heart failure in African American patients. The product under
investigation is BiDil(R), a combination tablet containing hydralazine and
isosorbide dinitrate.
NitroMed has requested that MIMC provide a proposal to manage all tasks
associated with the initiation, execution and completion of one multicenter,
randomized, doubleblind, placebo-controlled trial in the United States. The
study assumptions used as the basis for preparing this proposal are as follows:
o [**]
o [**]
o [**]
o [**]
o [**]
o [**]
o [**]
o [**]
o [**]
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STUDY FEES
The fees for CRO services to be provided by MIMC are outlined in the following
table.
The fees for services outlined do not include pass-through costs associated with
the study. Pass through costs are expected for the following items:
o Printing costs for case report forms, study operations manual,
training materials and investigator meeting materials
o Mail charges
o Travel associated with study monitoring visits and face to face client
meetings
o Costs associated with the investigator meeting, including travel and
ground transportation, meeting rooms, and audio-visual equipment
rentals.
o Central IRB fees (if central IRB is utilized)
Due to the size and nature of this study, MIMC has priced the clinical
monitoring and project management services using a discounted full-time
equivalent (FTE) approach as opposed to pricing the project on a standard fee
for service approach. Utilizing the FTE approach, Nitromed is provided with a
dedicated team for the anticipated duration of the study to handle all
monitoring and project management services. Since the personnel are dedicated to
the BiDil(R) project, ad-hoc requests for study information and additional
monitoring visits are not billed as out of scope services unless additional
staff are required to deliver the additional services requested.
FEES FOR CRO SERVICES
BIDIL(R) IN THE TREATMENT OF HEART FAILURE
---------------------------------------------------------------------------------------------------------------------
TASK UNIT COST NUMBER OF UNITS TOTAL COST
---------------------------------------------------------------------------------------------------------------------
CLINICAL SERVICES
---------------------------------------------------------------------------------------------------------------------
Identify the Clinical Study Sites $[**]/selected site [**] $[**]
---------------------------------------------------------------------------------------------------------------------
Prepare Informed Consent Form -- 1 Model ICD $[**]
---------------------------------------------------------------------------------------------------------------------
Case Report Form (CRF) Design -- 1 CRF Set $[**]
---------------------------------------------------------------------------------------------------------------------
Investigator Meeting -- 1 meeting $[**]
---------------------------------------------------------------------------------------------------------------------
Investigator Fees $[**]/payment [**]payments $[**]
---------------------------------------------------------------------------------------------------------------------
Initiate, Monitor and Close-out [**] $[**]/CRA/month [**]CRAs, [**] months $[**]
Clinical Sites
---------------------------------------------------------------------------------------------------------------------
Provide Monitoring Reports and Site Included in initiation, monitoring and close-out $[**]
Contacts
---------------------------------------------------------------------------------------------------------------------
Quality Assurance $[**]/Audit [**]Audits $[**]
---------------------------------------------------------------------------------------------------------------------
Other Clinical Services
---------------------------------------------------------------------------------------------------------------------
Project Management $[**]/month [**] months $[**]
---------------------------------------------------------------------------------------------------------------------
Serious Adverse Event Reporting $[**]/SAE [**] SAEs $[**]
---------------------------------------------------------------------------------------------------------------------
Study Document Collection $[**]/site [**] sites $[**]
---------------------------------------------------------------------------------------------------------------------
Budget and Contract Development $[**]/site [**] sites $[**]
---------------------------------------------------------------------------------------------------------------------
Project Team Training -- 1 training session $[**]
---------------------------------------------------------------------------------------------------------------------
Records Retention $[**]/site [**] sites [**]
---------------------------------------------------------------------------------------------------------------------
SUBTOTAL - CLINICAL $[**]
---------------------------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------------------------------
DATA MANAGEMENT AND MEDICAL WRITING SERVICES
---------------------------------------------------------------------------------------------------------------------
Prepare Annotated Case Report Form [**]/unique CRF page [**]unique CRF pages $[**]
---------------------------------------------------------------------------------------------------------------------
Prepare the Database $[**]/unique CRF page [**]unique CRF pages $[**]
---------------------------------------------------------------------------------------------------------------------
Review CRF in-house prior to Data Entry [**]/patient [**] patients, [**] $[**]
page CRF
---------------------------------------------------------------------------------------------------------------------
Double-Key Data Entry $[**]/page [**]pages $[**]
---------------------------------------------------------------------------------------------------------------------
Compare and QA the Data [**]/patient [**] patients @[**]% $[**]
---------------------------------------------------------------------------------------------------------------------
Query Resolution $[**]/query [**] queries $[**]
---------------------------------------------------------------------------------------------------------------------
Statistical Analysis $[**]unique table [**]unique tables $[**]
$[**]/replicate table [**]replicate tables
---------------------------------------------------------------------------------------------------------------------
Provide Summary Tables in Word 2000 Included in statistical Analysis $[**]
---------------------------------------------------------------------------------------------------------------------
Provide Data Listings in SAS $[**]/listing [**] listings $[**]
---------------------------------------------------------------------------------------------------------------------
Provide Data in SAS Datasets $[**]/dataset [**] datasets $[**]
---------------------------------------------------------------------------------------------------------------------
Prepare Integrated Clinical-Statistical -- 1 report $[**]
Report in ICH Format
---------------------------------------------------------------------------------------------------------------------
Other Data Management Services [**]
---------------------------------------------------------------------------------------------------------------------
Prepare and program data validation [**]/unique CRF page [**]unique CRF pages $[**]
guidelines
---------------------------------------------------------------------------------------------------------------------
Coding of AEs, Concomitant Medications, $[**]/term [**] terms $[**]
concomitant diseases
---------------------------------------------------------------------------------------------------------------------
SUBTOTAL - DATA MANAGEMENT AND MEDICAL WRITING $[**]
---------------------------------------------------------------------------------------------------------------------
STUDY TOTAL $[**]
---------------------------------------------------------------------------------------------------------------------
EXHIBIT B
PAYMENT SCHEDULE
Payment #1 Due Upon Execution of Contract
$[**] less $[**] paid to date = $[**]
Payment #2 - #18 Due the 15th of each month from April, 2001
$[**] through August, 2002
Final Payment Upon Submission of Final Report
$[**]
EXHIBIT B
PAYMENT SCHEDULE
REVISED FOR AMENDMENTS #2 AND #3
Payment #1 Due Upon Execution of Contract
$[**] less $[**] paid to date = $[**]
Payments #2 - # 10 Due the 15th of each month from April, 2001
$[**] Through December 2001
Payments #11 - #18 "January 2002 - August 2002"
$[**]
Final Payment Upon Completion of Study
$[**]
AMENDMENT 1
July 23, 2001
Xx. Xxxx Xxx
Project Manager
NitroMed, Inc.
00 Xxx Xxxx Xxxxx
Xxxxxxx, XX 00000
RE: AHEFT Trial
Dear Xxxx:
The project team has asked me to address the costs anticipated for our
management of the clinical endpoint process. Although this was discussed during
the very early stages of our bid and budget assessments, the pricing was never
included in any formal document as we had not as yet finalized our scope of
responsibilities. We are now able to do so after our meeting last Thursday with
Xx. Xxxxxx, at which time we finalized how MIMC will function as the clinical
endpoint management team.
Section 7B of the operations manual speaks to this issue and we anticipate that
the ICAC will be presented with approximately [**] clinical endpoints for
adjudication. Our fee for this service is $[**]/endpoint and we will xxxx you on
a monthly basis as they are processed through our Safety Department.
We would also like to bring to your attention our development of our interim
analysis tables and listings which were not discussed or included in our
original Professional Service Agreement. We will address this with another
amendment when your planning is complete and we can make a full assessment of
the costs involved.
I have included our Amendment #1 for signature in order to proceed with the work
required to carry forward the ICAC operations. Please send one copy back to me
when signed for our files.
As always, thank you for your kind assistance.
Sincerely,
/s/ Xxxxx X. Xxxxxxx
Xxxxx X. Xxxxxxx
Executive Director of Administration
Encl.
AMENDMENT 2
CLIENT AUTHORIZATION
CHANGE IN SCOPE OF WORK
The purpose of this notice is to inform NITROMED that MIMC has been requested to
provide services not anticipated in the original budget estimates or any revised
budget estimates to date. So that we can meet the established time frame, MIMC
has started work or will soon start work on the request. To authorize this work,
please sign this form and return it to Xxxxx Xxxxxxx, Executive Director of
Administration.
If you have any questions or would like to make changes, please call at (301)
000-0000.
----------------------------------------------------------------------------------------------------------------------
DESCRIPTION OF CHANGES IN SCOPE OF WORK - AMENDMENT #2
----------------------------------------------------------------------------------------------------------------------
SPONSOR: Nitromed
PERSON REQUESTING CHANGE IN SCOPE OF WORK: Project Team
PROJECT NUMBER: NIBIUMI PROTOCOL NUMBER: AHEFT
JOB CODE: 106
NATURE OF CHANGE IN SCOPE OF WORK: addition of "call center" center" activities per attached
REQUEST START DATE: 11/7/01 REQUESTED END DATE: TBD
----------------------------------------------------------------------------------------------------------------------
Estimated cost of change:
1. Estimated cost of change in scope of work: $[**]+ monthly fees of $[**] + per call of $[**] and per data entry
of $[**]
2. Existing budget for project: $[**] plus endpoints
3. Revised budget for project: $[**] plus endpoints, monthly fees, calls, data entry
----------------------------------------------------------------------------------------------------------------------
NITROMED MIMC
/s/ Xxx Xxxxxx /s/ Xxxxx X. Xxxxxxx
-------------------------- -----------------------------
Xxxxx X. Xxxxxxx
11/8/01 11/7/01
-------------------------- -----------------------------
Date Date
AMENDMENT 2
BUDGET VARIABLE DEFINITION
ONE TIME FEES
Project Setup
Project Management Charge (One Time Fee) for systems development, process
setup, creation of worksheets, etc.
Phone line setup
IT charge (One Time Fee) for setup of Phone line
Voice mail box setup for after hour calls
IT charge (One Time Fee) for setup of voice mail system
Database Setup
Data Management charge (One Time Fee) for setup of tracking
database/spreadsheets for data entry
Cordless Telephone
IT charge (One Time Fee) for purchase of cordless phone for call center
TRAINING FEE
Training of Operator
Project Management Charge for training of call center Operators. (Per
Training).
MONTHLY FEES
Phone line charge
Corporate Overhead charge (per month) for telephone line for call
center
Maintain phone lines
Corporate Overhead charge (per month) for monthly maintenance of call
center telephone line
Project Management
Project Management charge (per month) for supervisory management of
call-in center
PER CALL FEE
CALL MANAGEMENT
Call Center charge (Per Call) which includes. Answering call (or call
back), filling in worksheet, faxing call worksheet to appropriate
site, 1 week follow up with site to determine status of Call Center
charge (Per Call) which includes. Answering call (or call back),
filling in call worksheet, faxing call worksheet to appropriate site,
1 week follow up with site to determine status of patient appointment.
DATA ENTRY
Data Management charge (per call) for data entry of call-in worksheet.
AMENDMENT 2
ELEMENTS OF PROPOSAL
o Medifacts will [**].
o Medifacts will [**].
o Medifacts Clinical Staff will [**].
o A data collection/patient interview form will [**].
o Medifacts staff will [**].
o [**].
AMENDMENT 2
NITROMED
Call Center Budget
November 2, 2001
Assumptions
---------------------------------------------------------
Operators [**]
---------------------------------------------------------
---------------------------------------------------------
Duration (months) [**]
---------------------------------------------------------
---------------------------------------------------------
Calls per month (estimated) [**]
---------------------------------------------------------
---------------------------------------------------------
Total calls (estimated) [**]
---------------------------------------------------------
Description Unit Cost Description # of Units Total One Time Fees
One Time Fees
----------------------------------------------------------------------------------------------------------
Project Setup $[**] One time fee 1 $[**]
----------------------------------------------------------------------------------------------------------
Phone line setup $[**] One time fee 1 $[**]
----------------------------------------------------------------------------------------------------------
Voice mail box setup for after hour calls $[**] One time fee 1 $[**]
----------------------------------------------------------------------------------------------------------
Database Setup $[**] One time fee 1 $[**]
----------------------------------------------------------------------------------------------------------
Cordless Telephone $[**] One time fee 1 $[**]
----------------------------------------------------------------------------------------------------------
Training Fee
----------------------------------------------------------------------------------------------------------
Training of Operator $[**] per day 1 $[**] $[**]
----------------------------------------------------------------------------------------------------------
Monthly Fees
----------------------------------------------------------------------------------------------------------
Phone line charge $[**] per month 1 $[**]
----------------------------------------------------------------------------------------------------------
Maintain phone lines $[**] per month 1 $[**]
----------------------------------------------------------------------------------------------------------
Project Management $[**] per month 1 $[**] $[**]
----------------------------------------------------------------------------------------------------------
Per Call Fee
----------------------------------------------------------------------------------------------------------
Call Management $[**] Per Call [**] $[**]
----------------------------------------------------------------------------------------------------------
Data Entry $[**] Per Call [**] $[**]
----------------------------------------------------------------------------------------------------------
First Month Total Estimated Cost $[**] $[**]
Second Month Total Estimated Cost $[**]
Pass Through Costs
Phone call charge
Accounting
Miscellaneous
AMENDMENT 3
CLIENT AUTHORIZATION
CHANGE IN SCOPE OF WORK
The purpose of this notice is to inform NITROMED, INC. that MIMC has been
requested to provide services not anticipated in the original budget estimates
or any revised estimates to date. So that we can meet the established time
frame, MIMC has started work or will soon start work on the request. To
authorize this work, please sign this form and return it to Xxxxx Xxxxxxx,
Executive Director of Administration.
If you have any questions or would like to make changes, please call at (301)
000-0000.
================================================================================
DESCRIPTION OF CHANGES IN SCOPE OF WORK - AMENDMENT #3
================================================================================
SPONSOR: NitroMed, Inc.
PERSON REQUESTING CHANGE IN SCOPE OF WORK: X. Xxxxxxxxx
PROJECT NUMBER: NIBIUM1 PROTOCOL NUMBER:
JOB CODE: 106
NATURE OF CHANGE IN SCOPE OF WORK:
1. Identify [**] additional sites $ [**]
2. [**] additional unique CRF pages $ [**]
3. Initiate, Monitor and Close-Out Sites additional
sites $ [**]
4. Study Document Collection - [**] additional
sites $ [**]
5. Budget/Contracts - [**] additional sites $ [**]
6. Project Team Training at AHA $ [**]
7. Records Retention - [**] additional sites $ [**]
8. Annotated CRF - [**] additional pages $ [**]
9. Preparation of database -[**] additional
CRF pages $ [**]
10. Delete Statistical/Analysis - unique tables ($[**]) T. Archibault
11. Delete Statistical/Analysis - unique listings ($[**]) T. Archibault
12. Delete Data Listings in SAS ($[**]) T. Archibault
13. Provide Data in SAS Datasets for [**]
additional unique listings $ [**]
14. Prepare and program data validation
guidelines for [**] additional unique pages $ [**]
15. Revisions to database [**]
16. Delete Clinical Statistical Report [**]X. Xxxxxxxx
17. Review/QA clinical report [**]
AMENDMENT 3
================================================================================
REQUESTED START DATE: ASAP REQUESTED END DATE: end of contract period
================================================================================
Estimated cost of change:
1. Estimated cost of change in scope of work: $[**]
2. Existing budget for project: $[**]
3. Revised budget for project: $[**]
================================================================================
MIMC
/s/ Xxxxx X. Xxxxxxx
------------------------- ------------------------------------
Xxxxx X. Xxxxxxx
-------------------------
Title Executive Director of Administration
12/18/01
------------------------- ------------------------------------
Date Date
AMENDMENT 3
NitroMed
CHARGE ORDER COMPARISON
Original Original Variance
Unit Number of Total Revised Number Revised from
Service Cost Units Cost of Units Total Cost Original Cost
------- ---- ----- ---- -------- ---------- -------------
INFORMATION TO BE REDACTED IN ITS ENTIRETY.
AMENDMENT 4
APPENDIX TO
"DESCRIPTION OF CHANGES IN SCOPE OF WORK - AMENDMENT #4"
BETWEEN NITROMED, INC. AND MIMC, INC.
In signing the attached "Description of Changes in Scope of Work - Amendment #4"
(the "Agreement") Nitromed, Inc. and MIMC, Inc. (d.b.a. Medifacts International)
agree to the terms detailed below. This Appendix, and attached budget, shall
form an integral component of the Description of Changes in Scope of Work -
Amendment #4, and collectively all three documents shall form an integral part
of the governing contract signed by Nitromed, Inc. and MIMC, Inc., dated May 9,
2001.
TARGET ENROLLMENT DATES
The parties to the Agreement establish the following target enrollment
timelines.
-----------------------------------------------------------------------------------------------------------
TOTAL NO. OF PATIENTS
NO. OF PATIENTS RANDOMIZED
RANDOMIZED PER MONTH (SINCE STUDY INCEPTION)
MONTH (COLUMN B) (COLUMN C)
-----------------------------------------------------------------------------------------------------------
August 31, 2002 [**] [**]
-----------------------------------------------------------------------------------------------------------
September 30, 2002 [**] [**]
-----------------------------------------------------------------------------------------------------------
October 31, 2002 [**] [**]
-----------------------------------------------------------------------------------------------------------
November 30, 2002 [**] [**]
-----------------------------------------------------------------------------------------------------------
December 31, 2002 [**] [**]
-----------------------------------------------------------------------------------------------------------
January 31, 2003 [**] [**]
-----------------------------------------------------------------------------------------------------------
Regarding the goal of [**] randomized patients attained by January 2003, both
parties to this Agreement concur that "Intervention Activities" managed,
sponsored, and paid for by Nitromed, Inc. shall contribute a certain number of
randomized patients to the total of [**] patients. The parties agree that the
aggregate result of these Intervention Activities shall be not less than 35
randomized patients between the period of August 1, 2002 - January 31, 2003.
Should the Intervention Activities contribute fewer than [**] randomized
patients between the noted dates, then the target date for enrolling the [**]th
patient shall become February 28, 2003.
Intervention Activities are understood to include, but not necessarily be
limited to, patients randomized due to: "Grand Rounds" performed by Nitromed,
Inc., media and public relations campaigns, Core Solutions relationship and/or
activities facilitated by [**], floating coordinators, and other
activities initiated and paid for by Nitromed, Inc.
BILLING OF CLINICAL RESEARCH ASSOCIATES
As delineated in the attached budget, which forms an integral part of this
Agreement, Medifacts International shall xxxx CRA's at a baseline rate of
$[**]/hour through completion of enrollment of the [**]th patient. The parties
intend enrollment to be completed in January 2003. In such instances when the
target enrollment numbers are attained in a given month, Medifacts International
shall xxxx CRA's at a rate of $[**]/hour for that month. Attainment of target
enrollment numbers shall be defined as when, during a given month, the number of
patients randomized is equal to or greater than the aforementioned monthly
targets in Column B.
In all instances, should [**] patients be randomized by January 31, 2003,
Medifacts International shall receive a CRA rate of $[**]/hour for all CRA's,
retroactive to August 1, 2002. Should Nitromed Intervention Activities yield
fewer than [**] randomized patients, then the enrollment target timeline shall
become February 28, 2003. In such an instance, should the [**]th patient be
randomized by February 28, 2003, Nitromed, Inc. shall pay a CRA rate of
$[**]/hour applicable to all CRA's, starting August 1, 2002.
The attached budget includes the CRA baseline-billing rate of $[**]/hour. In
instances when monthly enrollment targets are attained, a billing adjustment
shall be applied to the subsequent month's invoice provided to Nitromed, Inc. by
Medifacts International. Such a retroactive billing shall result in the
effective billing rate applied to CRA's being equal to $[**]/hour.
In agreeing to the terms of this Agreement, both parties acknowledge that should
monthly enrollment targets not be attained in accordance with the above
timelines, the reduced $[**]/hour CRA billing rate shall be applied. No other
remedies shall be applied. In no situation shall anything in this Agreement be
understood to communicate that non-attainment of enrollment targets results in a
violation of this Agreement or the governing contract.
RECONCILIATION OF `FIRST CONTRACT' FEES
It is agreed that Medifacts International shall provide Nitromed, Inc. a
reconciliation of work completed under the original contract, which expires July
31, 2002. Medifacts International shall provide Nitromed, Inc. this
reconciliation no later than September 15, 2002. Nitromed, Inc. shall then make
a final reconciling payment to, or receive a credit from, Medifacts
International for work performed under the contract through July 31, 2002 no
later than October 15, 2002.
$[**]FINAL PAYMENT HOLDBACK
The parties to this Agreement agree to a final holdback payment amount under
this Agreement of $[**]. This holdback amount shall be due and payable to
Medifacts International no later than 14 days following database lock and
database transfer to Nitromed, Inc.
This $[**] shall be comprised of two components:
o [**]
o [**]
These terms are reflected in the attached budget.
QUARTERLY RECONCILIATION
The parties to this Agreement agree to reconcile the Agreement budget on a
quarterly basis. Medifacts International shall provide Nitromed, Inc. a
quarterly reconciliation no later than the last day of the month following the
close of each calendar quarter. The first quarterly reconciliation shall be for
the period August-September.
REWARD FOR EARLY STUDY COMPLETION
If the 600th patient is randomized prior to January 31, 2003, then the total
cost of the AHEFT study, as defined in the attached budget, should decrease as
fewer resources are required to complete the study. Should such an event occur,
and this results in the AHEFT study reaching completion prior to the currently
anticipated completion date of November 2003, Medifacts International shall
receive a bonus payment from Nitromed, Inc. The bonus payment shall be equal to
[**]% of the total savings resultant from the early completion of enrollment.
Savings shall be defined in reference to the existing attached budget, adjusted,
as the case may be, for subsequent changes to project scope.
For example, if all recruitment would be completed by December 31, 2002 then the
parties would expect to complete the project one month sooner, decreasing
project cost by one month worth of activities. In such an instance, Medifacts
would receive a bonus equal to half of the total savings.
CANCELLATION OF CONTRACT
The terms of this section shall be understood to amend the terms that affect
Nitromed's right to cancel the aforementioned May 9, 2001 governing contract,
and thereby this Agreement. Specifically:
1. If Nitromed, Inc. elects to cancel this Agreement before September 1, 2002,
then the parties to this Agreement agree to the following: (i) a mutually
agreed-up upon `wind-down' period for the project shall be agreed between
Nitromed, Inc. and Medifacts International. During this wind-down period
the billing rates and terms currently defined in this Agreement shall be
utilized; and (ii) a cancellation fee of $[**]shall be paid by Nitromed,
Inc. to Medifacts International no later than 14 days following the
completion of the project wind-down; and (iii) Medifacts International
shall be entitled to receive payment for all work actually performed, for
out-of-pocket expenses actually incurred, and for non-cancelable
commitments actually entered into on behalf of Nitromed, Inc. The
aforementioned monthly holdback amount of $[**] shall be considered work
actually performed, and therefore in instances of contract cancellation,
Nitromed, Inc. shall pay Medifacts International amounts held back in
months prior to any such cancellation.
2. If Nitromed, Inc. elects to cancel this Agreement after September 1, 2002,
then the parties to this Agreement agree to the following: (i) a mutually
agreed-up upon `wind-down' period for the project shall be agreed between
Nitromed, Inc. and Medifacts International. During
this wind-down period the billing rates and terms currently defined in this
Agreement shall be utilized; and (ii) a cancellation fee equal to [**]% of
the balance of contract fees as defined in this Agreement shall be paid by
Nitromed, Inc. to Medifacts International no later than 14 days following
the completion of the project wind-down; and (iii) Medifacts International
shall be entitled to receive payment for all work actually performed, for
out-of-pocket expenses actually incurred and for non-cancelable commitments
actually entered into on behalf of Nitromed, Inc. The aforementioned
monthly holdback amount of $[**]shall be considered work actually
performed, and therefore in instances of contract cancellation, Nitromed,
Inc. shall pay Medifacts amounts held back in months prior to any such
cancellation.
OTHER CONSIDERATIONS
3. Medifacts International agrees to maintain the rates defined in the
attached budget throughout the duration of the study, i.e., the annual
increase in rates applicable with the start of the new year shall not be
applied to this study.
4. If incremental CRA's are required, Nitromed, Inc. and Medifacts
International shall do so through a change order, and those CRA's shall be
billed at $[**]/hour.
NITROMED, INC. MEDIFACTS INTERNATIONAL
/s/ Xxxxxx Xxxxxx /s/ Xxxxx X. Xxxxxxx
---------------------------------- ---------------------------------
Name: Xxxxxx Xxxxxx Name: Xxxxx X. Xxxxxxx
7/16/2002 7/17/02
---------------------------------- ---------------------------------
Date: Date:
AMENDMENT 4
NITROMED A-HEFT TRIAL
AUGUST 1, 2002 - NOVEMBER 30, 2003
BUDGET SUMMARY
------------------------------------------------
Number of
Units/Monthly
Unit Cost FTEs Total Cost
------------------------------------------------
---------------------------------------------------------------- ------------------------------------------------
I. CLINICAL SERVICES
------------------------------------------------
Identify the Clinical Study Sites $ 760 [**] [**]
===
------------------------------------------------
Prepare informed Consent Form
------------------------------------------------
Case Report Form (CRF) Design
------------------------------------------------
Investigator Meeting
------------------------------------------------
Investigator Fees $[**] [**] [**]
------------------------------------------------
CRA's (Baseline rate $[**]/hour during enrollment) $[**] [**] [**]
------------------------------------------------
Floating Coordinators $[**] [**] [**]
------------------------------------------------
Lead CRA $[**] [**] [**]
------------------------------------------------
RA's $[**] [**] [**]
------------------------------------------------
Project Manager $[**] [**] [**]
------------------------------------------------
Data Manager $[**] [**] [**]
------------------------------------------------
Database Programmer $[**] [**] [**]
------------------------------------------------
Safety Director $[**] [**] [**]
------------------------------------------------
Safety Associate $[**] [**] [**]
------------------------------------------------
Quality Assurance Audits $[**] [**] [**]
------------------------------------------------
SAEs/CEPs $[**] [**] [**]
------------------------------------------------
Study Document Collection $[**] [**] [**]
------------------------------------------------
Budget and Contract Development $[**] [**] [**]
------------------------------------------------
Records Retention $[**] [**] [**]
------------------------------------------------
Record Retention for Terminated Sites $[**] [**] [**]
------------------------------------------------
SUBTOTAL-CLINICAL SERVICES [**]
------------------------------------------------
III. DATA MANAGEMENT AND MEDICAL WRITING SERVICES
------------------------------------------------
Prepare Annotated Case Report Form
------------------------------------------------
Prepare the Database
------------------------------------------------
Review CRF in-house prior to Data Entry or after DE with $[**]/
DVG output CRF page [**] [**]
------------------------------------------------
Double-Key Data Entry $[**]/page [**] [**]
------------------------------------------------
Compare and QA the Data $[**]/patient [**] [**]
------------------------------------------------
Query Resolution $[**]/query [**] [**]
------------------------------------------------
Statistical Analysis
------------------------------------------------
Statistical Analysis
------------------------------------------------
Provide Summary Tables in Word 2000
------------------------------------------------
Provide Data Listings in SAS
------------------------------------------------
Provide Data in SAS Datasets
------------------------------------------------
Prepare Integrated Clinical-Statistical Report in ICH
Format
------------------------------------------------
Prepare and program data validation guidelines
------------------------------------------------
Coding of AEs, Concomitant Medications, concomitant $[**]/term [**] [**]
diseases
------------------------------------------------
Revisions to Database, DVGs for amendments 3, 4, 5
------------------------------------------------
Statistical Plan
------------------------------------------------
Provide Shell Report
------------------------------------------------
Provide Tracking Database for Referring Physicians
------------------------------------------------
SUBTOTAL-DATA MANAGEMENT AND MEDICAL WRITING [**]
------------------------------------------------
III. ADJUSTMENTS
------------------------------------------------
Amendment #1 CEP Processing Estimated
------------------------------------------------
Amendment #2 VNR Call Center Management Estimated
------------------------------------------------
SUBTOTAL-ADJUSTMENTS
------------------------------------------------
TOTAL [**]
----------------------------------------------------------------------------------------------------------------------
----------------------------------------------------------------------------------------------------------------------
NOTES:
1) Does not include [**] time. As agreed, to be treated on time & materials basis and billed separately
2) Pass-through expenses not included herein
----------------------------------------------------------------------------------------------------------------------
------------------------------------------------
AT RISK $[**]
-------------
TOTAL @[**] $[**]
------------------------------------------------
AMENDMENT 4
NITROMED A-HEFT
AUGUST 1, 2002 - NOVEMBER 30, 2003
SUPPORT CALCULATIONS AND PAYMENT SCHEDULE
2002 2002 2003
Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Total
------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ -----
PERSONNEL-
BASED FEES
TO BE REDACTED IN ITS ENTIRETY.
AMENDMENT 4
NITROMED A-HEFT
AUGUST 1, 2002 - NOVEMBER 30, 2003
SUPPORT CALCULATIONS AND PAYMENT SCHEDULE
2002 2002 2003
Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Total
------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ -----
PERSONNEL-
BASED FEES
TO BE REDACTED IN ITS ENTIRETY.
AMENDMENT 4
NITROMED A-HEFT TRIAL
AUGUST 1, 2002 - NOVEMBER 30, 2003
BUDGET SUMMARY
------------------------------------------------
Number of
Units/Monthly
Unit Cost FTEs Total Cost
------------------------------------------------
---------------------------------------------------------------- ------------------------------------------------
I. CLINICAL SERVICES
------------------------------------------------
Identify the Clinical Study Sites $ [**] [**] [**]
------------------------------------------------
Prepare informed Consent Form [**] [**]
------------------------------------------------
Case Report Form (CRF) Design [**] [**]
------------------------------------------------
Investigator Meeting [**] [**]
------------------------------------------------
Investigator Fees $ [**] [**] [**]
------------------------------------------------
CRA's (Baseline rate $80/hour during enrollment) $ [**] [**] [**]
==
------------------------------------------------
Floating Coordinators $ [**] [**] [**]
------------------------------------------------
Lead CRA $ [**] [**] [**]
------------------------------------------------
RA's $ [**] [**] [**]
------------------------------------------------
Project Manager $ [**] [**] [**]
------------------------------------------------
Data Manager $ [**] [**] [**]
------------------------------------------------
Database Programmer $ [**] [**] [**]
------------------------------------------------
Safety Director $ [**] [**] [**]
------------------------------------------------
Safety Associate $ [**] [**] [**]
------------------------------------------------
Quality Assurance Audits $ [**] [**] [**]
------------------------------------------------
SAEs/CEPs $ [**] [**] [**]
------------------------------------------------
Study Document Collection $ [**] [**] [**]
------------------------------------------------
Budget and Contract Development $ [**] [**] [**]
------------------------------------------------
Records Retention $ [**] [**] [**]
------------------------------------------------
Record Retention for Terminated Sites $ [**] [**] [**]
------------------------------------------------
SUBTOTAL-CLINICAL SERVICES [**]
------------------------------------------------
III. DATA MANAGEMENT AND MEDICAL WRITING SERVICES
------------------------------------------------
Prepare Annotated Case Report Form
------------------------------------------------
Prepare the Database
------------------------------------------------
[**] [**]
Review CRF in-house prior to Data Entry or after DE with
DVG output $[**]/CRF page
------------------------------------------------
Double-Key Data Entry $[**]/page [**] [**]
------------------------------------------------
Compare and QA the Data $[**]/patient [**] [**]
=
------------------------------------------------
Query Resolution $[**]/query [**] [**]
------------------------------------------------
Statistical Analysis [**]
------------------------------------------------
Statistical Analysis [**]
------------------------------------------------
Provide Summary Tables in Word 2000
------------------------------------------------
Provide Data Listings in SAS
------------------------------------------------
Provide Data in SAS Datasets
------------------------------------------------
Prepare Integrated Clinical-Statistical Report in ICH
Format
------------------------------------------------
Prepare and program data validation guidelines
------------------------------------------------
Coding of AEs, Concomitant Medications, concomitant $[**]/term [**] [**]
diseases
------------------------------------------------
Revisions to Database, DVGs for amendments 3, 4, 5
Statistical Plan
Provide Shell Report
------------------------------------------------
Provide Tracking Database for Referring Physicians
------------------------------------------------
SUBTOTAL-DATA MANAGEMENT AND MEDICAL WRITING [**]
------------------------------------------------
III. ADJUSTMENTS
------------------------------------------------
Amendment #1 CEP Processing Estimated
------------------------------------------------
Amendment #2 VNR Call Center Management Estimated
------------------------------------------------
SUBTOTAL-ADJUSTMENTS
------------------------------------------------
TOTAL [**]
---------------------------------------------------------------- ------------------------------------------------
----------------------------------------------------------------------------------------------------------------------
NOTES:
1) Does not include [**] time. As agreed, to be treated on time & materials basis and billed separately
2) Pass-through expenses not included herein
----------------------------------------------------------------------------------------------------------------------
Proposal for Clinical Trial Services
BiDil(R) in the Treatment of Heart Failure
AMENDMENT 5
CLIENT AUTHORIZATION
CHANGE IN SCOPE OF WORK
The purpose of this notice is to inform NITROMED, INC. that MIMC has been
requested to provide services not anticipated in the original budget estimates
or any revised budget estimates to date. So that we can meet the established
time frame, MIMC has started work or will soon start work on the request. To
authorize this work, please sign this form and return it to Xxxxx Xxxxxxx,
Executive Director of Administration.
If you have any questions or would like to make changes, please call at (301)
000-0000.
--------------------------------------------------------------------------------
DESCRIPTION OF CHANGES IN SCOPE OF WORK - AMENDMENT #5
--------------------------------------------------------------------------------
SPONSOR: Nitromed, Inc.
PERSON REQUESTING CHANGE IN SCOPE OF WORK: Xx. XxXxxx for the DSMB
PROJECT NUMBER: AHEFT PROTOCOL NUMBER:
JOB CODE: NIBIUM1
NATURE OF CHANGE IN SCOPE OF WORK:
1) Data listings for DSMB: services included testing the new page, writing a
test protocol, creating dummy data to be tested, entering dummy data into
the test database; program of page in 1st and 2nd key; production of page
into application; and writing and programming of validation checks
REQUESTED START DATE: ASAP REQUESTED END DATE: Completed
--------------------------------------------------------------------------------
Estimated cost of change:
1. Estimated cost of change in scope of work: $[**]
2. Existing budget for project: $[**]
3. Revised budget for project: $[**]
--------------------------------------------------------------------------------
NITROMED, INC. MIMC
/s/ Xxxxxx Xxxxxx /s/ Xxxxx X. Xxxxxxx
---------------------------- ------------------------------------
Xxxxx X. Xxxxxxx
Executive Director of Administration
11/8/2002 10/29/02
---------------------------- ------------------------------------
Date Date
RFP NITRO2 Jan 01-001
January 18, 2001
Proposal for Clinical Trial Services
BiDil(R) in the Treatment of Heart Failure
AMENDMENT 6
CLIENT AUTHORITIES
CHANGE IN SCOPE OF WORK
The purpose of this notice is to inform NITROMED, INC. that MIMC has been
requested to provide services not anticipated in the original budget estimates
or any revised budget estimates to date. So that we can meet the established
time frame, MIMC has started work or will soon start work on the request. To
authorize this work, please sign this form and return it to Xxxxx Xxxxxxx,
Executive Director of Administration.
If you have any questions or would like to make changes, please call at (301)
000-0000.
--------------------------------------------------------------------------------
DESCRIPTION OF CHANGES IN SCOPE OF WORK - AMENDMENT # 6
--------------------------------------------------------------------------------
----------------------------------------------------------------------------------------
SPONSOR: Nitromed, Inc.
PERSON REQUESTING CHANGE IN SCOPE OF WORK: Xxxxxx Xxxxxx
PROJECT NUMBER: AHEFT PROTOCOL NUMBER:
JOB CODE: NIB-UM2
NATURE OF CHANGE IN SCOPE OF WORK:
Per email from Xxx Xxxxxx to Xxxxxx Xxxxxx dated December 10, 2002
1) 2 additional CRAs - $[**]
2) Increase in SAE/CEP volume- $[**]
3) Increase in Data Management time - $[**]
REQUESTED START DATE: December 1, 2002 REQUESTED END DATE: February 28, 2003
----------------------------------------------------------------------------------------
Estimated cost of change:
1. Estimated cost of change in scope of work: $[**]
2. Existing budget for project: $[**]
3. Revised budget for project: $[**]
--------------------------------------------------------------------------------
NITROMED, INC. MIMC
/s/ Xxxxxx Xxxxxx /s/ Xxxxx X. Xxxxxxx
---------------------------- ------------------------------------
Xxxxx X. Xxxxxxx
PRESIDENT EXECUTIVE DIRECTOR OF ADMINISTRATION
---------------------------- ------------------------------------
Title
12/11/2002 12/10/02
---------------------------- ------------------------------------
Date Date
RFP NITRO2 Jan 01-001
January 18, 2001
Proposal for Clinical Trial Services
BiDil(R) in the Treatment of Heart Failure
AMENDMENT 6
The details delineated in the below email dated November 27, will, with one
exception govern change order 6. The exception is that the duration will change.
Instead of running for four months, the effort described below will run for
three months - for the period December 1 - February 28. Therefore, the total
amounts due per each section are amended to read as follows:
Two additional CRAs: $[**]
===
Increase in SAE/CEP: $[**]
Increase in DM time: $[**]
Total: $[**]
TWO ADDITIONAL CRAS
As the site target has grown from [**] sites originally estimated under the
current contract, to the [**] now being pursued, the level of CRA demand to
oversee the sites has also grown. For this extra effort, an additional [**]CRAs
are needed for the period of December 1 - March 31.
Financial: Monthly CRA rate equals $[**]each month = $[**] x 4 months = $[**].
Monthly amount of $[**] to be included in monthly xxxxxxxx paid on 15th of each
month.
INCREASE IN SAE/CEP VOLUME
Volume of SAE/CEP volume is greater than expected. This is due partly to fact
that previously expected to have to process only heart-failure events, now must
process all events. In speaking with Xxxxx and Xxxxxxx, they estimate the volume
of SAE/CEPs processed in August and September to be representative of what may
be seen through the end of March. The projection was for [**] events per month,
whereas in August and September [**] events were processed. This is an increase
of [**] events per month.
Financial: [**] events x $[**]per event = $[**]x 4 months = $[**]. Monthly
amount of $[**]to be included in monthly xxxxxxxx paid on 15th of each month.
INCREASE IN DM TIME
During the DSMB in August, it was determined that additional snapshots of data
would be helpful/required. This included such areas as concomitant medications
and drug accountability and exposure. Additionally, the Medifacts DM team fields
many requests from Nitromed biostatisticians to look at end points. Both of
these items result in data being cleaned and reviewed on more than one occasion,
and the project DM plan did not anticipate such items. Financial: [**]
additional Data Manager x $[**]per month x 4 months = $[**]Monthly amount of
$[**] to be included in monthly xxxxxxxx paid on 15th of each month.
RFP NITRO2 Jan 01-001
January 18, 2001
Proposal for Clinical Trial Services
BiDil(R) in the Treatment of Heart Failure
AMENDMENT 7
CLIENT AUTHORITIES
CHANGE IN SCOPE OF WORK
The purpose of this notice is to inform NITROMED, INC. that MIMC has been
requested to provide services not anticipated in the original budget estimates
or any revised budget estimates to date. So that we can meet the established
time frame, MIMC has started work or will soon start work on the request. To
authorize this work, please sign this form and return it to Xxxxx Xxxxxxx,
Executive Director of Administration.
If you have any questions or would like to make changes, please call at (301)
000-0000.
--------------------------------------------------------------------------------
DESCRIPTION OF CHANGES IN SCOPE OF WORK - AMENDMENT #7
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
SPONSOR: Nitromed, Inc.
PERSON REQUESTING CHANGES IN SCOPE OF WORK: Xxxxxx Xxxxxx
PROJECT NUMBER: AHEFT PROTOCOL NUMBER:
JOB CODE: NIBI-UM2
NATURE OF CHANGE IN SCOPE OF WORK
As per Amendment #6, continue provisions for one additional month
REQUESTED START DATE: ASAP REQUESTED END DATE: end of March, 2003
--------------------------------------------------------------------------------
Estimated cost of change:
1. Estimated cost of change in scope of work: $[**]
2. Existing budget for project: $[**]
3. Revised budget for project: $[**]
--------------------------------------------------------------------------------
NITROMED, INC. MIMC
/s/ Xxxxxx Xxxxxx /s/ Xxxxx X. Xxxxxxx
---------------------------- ------------------------------------
Xxxxx X. Xxxxxxx
PRESIDENT EXECUTIVE DIRECTOR OF ADMINISTRATION
---------------------------- ------------------------------------
Title
2/25/2003 2/14/03
---------------------------- ------------------------------------
Date Date
RFP NITRO2 Jan 01-001
January 18, 2001
