CLINICAL RESEARCH AGREEMENT
This Agreement, entered into as of the 15th day of July 1996 ("Effective
Date"), between ICON ("ICON"), a clinical research corporation having its
principal place of business at 000 Xxxx Xxxxxxxxxx Xxxx, Xxxxx 000,
Xxxxxxxxxx, XX 00000, and Xxxxxxxxxx Laboratories, Inc. ("Xxxxxxxxxx")
having its principal place of business at 0000 Xxxx Xxxxxxxx Xxxxxxxxx,
Xxxxxx, XX 00000-0000.
WITNESSETH:
WHEREAS, ICON is engaged in the business of organizing, managing,
monitoring and reporting clinical research programs; and
WHEREAS, Xxxxxxxxxx is engaged in the development of pharmaceutical
products; and
WHEREAS, Xxxxxxxxxx desires ICON to initiate, manage, monitor and
coordinate a clinical study program entitled:
Protocol 9009: A Double-Blind, Randomized, Placebo-Controlled Study of
the Safety and Efficacy of Three Dose Regimens of Aliminase(TM) in the
Treatment of Active Ulcerative Colitis.
and ICON desires to perform such activities relating to the clinical
study program, all in accordance with the terms and conditions of this
Agreement;
NOW, THEREFORE, the parties agree as follows:
SECTION 1
DEFINITIONS
As used in this Agreement, the following terms shall have the meanings
set forth below:
1.1 "Study" shall mean the clinical study program known as:
Protocol 9009: A Double-Blind, Randomized, Placebo-Controlled Study of
the Safety and Efficacy of Three Dose Regimens of Aliminase in the
Treatment of Active Ulcerative Colitis.
1.2 "Protocol" shall mean the clinical protocol 9009 for the Study
attached hereto as Exhibit C and incorporated herein by reference.
1.3 "Study Drug" shall mean the investigational drug Aliminase .
1.4 "Declaration" shall mean the Declaration of Helsinki, and subsequent
amendments.
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1.5 "GCP Guidelines" shall mean Good Clinical Practices as defined by
the United States Food and Drug Administration.
1.6 "IRB" shall mean the Institutional Review Board as that term is
defined under the Federal Food, Drug and Cosmetic Act.
1.7 "Regulatory Agency" shall collectively mean the United States Food
and Drug Administration.
1.8 "Monitored Site" shall mean a hospital or clinic of a practicing
physician selected by ICON to conduct the Study. Such Monitored Site
shall provide patients for the Study, administer Study Drug to such
patients, and record the patient data for the Study, in accordance with
the Protocol.1.9 "Qualified Patient" shall mean any patient who meets
the criteria for continuing participation in the Study, as set forth more
fully in Protocol 9009, signs an IRB-approved informed consent form for the
Study, and receives Study Drug.
1.10 "Completed Patient" shall mean any Qualified Patient who completes
the Study and who, by reason of Protocol adherence and the completeness
and accuracy of the data contained in the case report form ("CRF") can be
included in the pool of cases whereby the clinical efficacy and safety
of Study Drug may be assessed.
SECTION 2
SCOPE OF SERVICES
2.1 Services Under the terms and conditions hereof, ICON shall initiate,
manage and monitor the Study. The Study shall involve the participation
of 280 Qualified Patients and the Study shall be considered completed
once completed CRFs for 280 such Patients are transferred to Xxxxxxxxxx.
The specifications and assumptions for the Study are attached as Exhibit
A.
2.2 ICON Responsibilities ICON's services hereunder are as further
described in Section 3 and 4 below. ICON shall give due consideration to
any consultation or advice that Xxxxxxxxxx from time to time may wish to
make respecting ICON's conduct of the Study.
SECTION 3
CLINICAL MONITORING RESPONSIBILITIES
3.1 Conduct of Program. ICON shall carry out its obligations in
accordance with the terms and conditions of this Agreement, the mandates
of the IRB, the Declaration, the GCP Guidelines and all applicable
national and local laws, and guidelines. ICON shall conduct the Study in
a competent and professional manner consistent with the current state of
clinical research. ICON shall at all times consult with Xxxxxxxxxx on
matters regarding safety considerations and Study implementation, and
will adhere to Xxxxxxxxxx'x advice concerning same.
2
3.2 Staffing. ICON shall be responsible for providing all clinical
research personnel involved in Study monitoring undertaken by it
hereunder, as well as any necessary replacements. ICON shall provide
clinical research associates (CRAs), qualified by education and
experience to monitor clinical studies, all of whom will be exclusively
dedicated to the study for the period of this Agreement.
3.3 Establishment of IRB. ICON shall ensure that an appropriate IRB
established and constituted in accordance with GCP Guidelines, oversees
the conduct of the Study at each site and that ICON's initiation,
management, monitoring and coordination of the Study shall comply with
the mandates of such IRB in respect thereof.
3.4 Informed Consent; CRFs; Supplies. ICON shall prepare a standard form
of informed consent for patients to sign prior to their participation in
the Study, which informed consent shall include the patient's
authorization for Xxxxxxxxxx, its representative or governmental
agencies, including the Regulatory Agency, to review the patient's
medical records and CRFs, and which shall be subject to the approval of
Xxxxxxxxxx and the IRB prior to any use thereof. Xxxxxxxxxx shall have
the responsibility of designing, reviewing and printing the CRFs.
Xxxxxxxxxx shall be responsible for providing adequate Study Drug,
appropriately packaged, as required by the Protocol, and shall be
responsible for shipment of the Study Drug to the Monitored Sites.
3.5 Investigator Meetings
The costs of investigator meetings, if required, shall be paid by
Xxxxxxxxxx separately from and in addition to ICON's fees as set out
under Section 6.1 of this Agreement.
3.6 Monitoring Visits
(a)During the term of this Agreement, ICON personnel shall conduct
regular on-site monitoring visits for all of the enrolled patients at
Monitored Sites. Such visits shall be scheduled as considered necessary
by ICON in consultation with Xxxxxxxxxx for proper conduct of the Study,
and the interval between successive visits will not normally exceed six
weeks. In addition, ICON shall make regular telephone contact, at least
once weekly, with each Monitored Site for a status report on the conduct
of the Study.
(b)Xxxxxxxxxx or a Xxxxxxxxxx designee may conduct any additional
monitoring and/or quality assurance visits if Xxxxxxxxxx so desires and
such Xxxxxxxxxx personnel or Xxxxxxxxxx designee may be accompanied by
ICON personnel on these visits.
(c)In the event an ICON clinical monitor is unable, for any reason during
the term of this Agreement, to fulfill his/her supervisory role in the
monitoring responsibilities set forth herein, ICON shall replace the
clinical monitor with a suitably qualified replacement monitor at no
additional cost to Xxxxxxxxxx.
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3.7 Monitoring Procedures. The Monitored Sites shall be monitored by
ICON in order to ensure that the Study, as conducted at each Monitored
Site, complies with the requirements of the Protocol, the mandates of the
IRB, the Declaration, the GCP Guidelines and all applicable national and
local regulations and guidelines, as well as to monitor the following:
(a) the progress of the Study as conducted at each Monitored Site; (b)
the continued acceptability of each Monitored Site and its clinical
investigator; (c) the adequate maintenance of required records at each
Monitored Site, which includes source documents, Monitored Site copies of
CRFs, Study initiation documents, correspondence, and monitor records,
(d) the occurrence of any adverse events; (e) the quality of data
preparation at each Monitored Site including but not limited to
verification that CRFs are complete, authentic and accurate; (f)
information regarding any Qualified Patients who do not complete the
Study; (g) drug inventory and accountability records of each Monitored
Site, (h) the records of biological sampling and records of sample
shipments at each Monitored Site; and (i) any such additional responsibilities
as are hereafter agreed upon in writing by Xxxxxxxxxx and ICON. On a periodic
basis, or as requested in writing by Xxxxxxxxxx, ICON shall advise and consult
with Monitored Sites and/or their clinical investigators regarding questions
concerning the Protocol, the conduct of the Study, and the preparation of
data thereof.
3.8 Monitoring Visit Records. ICON shall maintain written records of
each monitoring visit conducted by it hereunder, with an accurate record
of each visit made to each Monitored Site by the Clinical Monitor or
his/her designees, as well as a record of any inspections conducted by
any governmental or Regulatory Agency. In no case shall a CRF be finally
removed from a Monitored Site prior to its verification by a monitoring
site visit.
3.9 Status Reports/Project Meetings ICON shall provide Xxxxxxxxxx with
monthly written reports on the progress of the Study, which reports shall
advise of any problems, delays or extraordinary incidents occurring in
the Study. Should Xxxxxxxxxx require ICON personnel to attend project
meetings at Xxxxxxxxxx, the cost of such meetings shall be paid for by
Xxxxxxxxxx, separately from and in addition to ICON's fees under the
terms of this Agreement.
3.10 Clinical/Statistical Report Xxxxxxxxxx shall be responsible for the
full clinical/statistical report.
3.11 Warranties ICON warrants that its activities shall be undertaken in
compliance with the Declaration, GCP Guidelines and all applicable
national and local laws, regulations and guidelines.
3.12 Regulatory Inspection Upon notification of an impending inspection
by any Regulatory Agency or other government authority at ICON's
premises, or at any Monitored Site, ICON shall notify Xxxxxxxxxx
immediately.
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3.13 Further Compliance Upon request by any authorized officer or
employee of any relevant Regulatory Agency, or other government
authority, ICON shall permit such officer or employee, at reasonable
times, to have access to and copy and verify any records and reports in
ICON's possession or under ICON's custody or control relating to the
Study, and shall submit such records or reports or copies thereof to the
said Regulatory Agency upon its request.
SECTION 4
ADDITIONAL RESPONSIBILITIES
4.1 Administrative Services ICON shall perform the following Study
administration services in conjunction with its monitoring
responsibilities with respect to each Monitored Site:
(a) Identification and verification of qualifications and experience of
prospective clinical investigators and submission of same to Xxxxxxxxxx.
ICON shall evaluate 35 appropriately qualified and experienced clinical
investigators of which 30 will be initiated for the Study.
(b) Coordination of Study initiation at each Monitored Site to assure
timely submission of appropriate documents and receipt of adequate
supplies to facilitate enrollment and commencement of the Study.
(c) Orientation and training of all clinical investigators and relevant
support personnel with regard to compliance with the Protocol and the
Declaration, the GCP Guidelines and all applicable national and local
laws, regulations and guidelines.
(d) Confirmation of clinical investigator performance with regard to the
following aspects of the Study conducted at the respective Monitored
Site: the number of patients enrolled in the Study, the number of
Qualified Patients participating in the Study, the number of Patients
resulting from the Study, and the number of serious or unexpected adverse
reactions occurring during the Study.
(e) Distribution to clinical investigators of safety information
regarding Study Drug, which information shall be provided to ICON by
Xxxxxxxxxx.
(f) Notification of the Monitored Site/IRB of any subsequent Protocol
amendments and of significant adverse events as provided for under
Section 9 below.
4.2 Other Services ICON shall also assist Xxxxxxxxxx in any other way
Carrington deems necessary or appropriate to coordinate with the
Regulatory Agencies, IRB, or Monitored Sites in their completion of the
Study and submission of Study data on a timely and satisfactory basis. If
any additional services requested by Xxxxxxxxxx result in extra costs to
ICON which are not covered by the terms of this Agreement, such
additional costs will be charged by ICON to Xxxxxxxxxx as they are
incurred (after prior discussion with Xxxxxxxxxx).
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SECTION 5
TERM AND TERMINATION
5.1 Term This Agreement shall, subject to Section 5.2 below, commence on
the Effective Date and continue for 12 months, or such date as 280
completed CRFs for Qualified Patients are obtained by ICON. The
termination date of the Study is defined as 7 days after ICON's
notification by Xxxxxxxxxx that patient recruitment is to cease.
5.2 Termination Not withstanding Section 5.1 above this Agreement may be
terminated as follows:
(a) Default. Notice by either party to the other party in the event such
other party materially breaches any provision of this Agreement, which
breach continues and is not remedied within thirty (30) calendar days
after the date of receipt of such notice.
(b) Insolvency. Notice of either party to the other party upon the
insolvency or bankruptcy of such other party.
(c) Notice. Xxxxxxxxxx or ICON may terminate this Agreement at any time
upon sixty (60) days prior written notice to the other party; provided,
however, that if the Study is terminated for reasons of patient safety,
the 60-day notice requirement shall not apply and termination shall be
effective immediately upon notification by telephone, which shall then be
followed by written confirmation.
5.3 Transfer of Data and Materials. All data and other information
resulting from the Study shall be the sole property of Xxxxxxxxxx and
shall be subject to Xxxxxxxxxx'x exclusive use, commercial or otherwise.
Upon the termination of this Agreement or the Study for any reason, ICON
shall provide for the return to Xxxxxxxxxx of all completed, partially
completed and unused CRFs, all unused supplies of Study Drug and all
other materials of Xxxxxxxxxx'x in ICON's and Monitored Sites' possession
or control, including but not limited to all data and other information
resulting from the Study, within sixty (60) days of such termination. In
the event that this Agreement or the Study is prematurely terminated,
ICON shall complete work on the Study as expeditiously as possible and in
accordance with Xxxxxxxxxx'x instructions and all applicable national and
local laws, regulations, and guidelines.
SECTION 6
PAYMENT
6.1 Payment Subject to the terms and conditions hereof, in
consideration for the services to be provided by ICON under the terms of
this agreement, Xxxxxxxxxx shall pay to ICON a fixed fee of $US2,123,218
(Two million, one hundred twenty-three thousand, two hundred and eighteen
US dollars). Such fee shall be paid in accordance with the following
schedule attached as Exhibit B.
6.2 Additional Payments
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6.2.1 Extension Period Payments
In the event the Study is not completed by ICON during the term of this
Agreement, for any of the following reasons, Xxxxxxxxxx shall have the
right to extend the period of the Study on a month-by-month basis, by
paying staff costs in the sum of $US($49,156)(Forty nine thousand, one
hundred and fifty six US dollars) plus expenses per month (or part of a
month), such payment to be made on or before the first day of each month
(or part of a month), so extended.
Such reasons are:
(a) Xxxxxxxxxx fails to provide the Study Drug, or other information or
materials required by the Protocol by one month from the date of this
agreement.
(b) Xxxxxxxxxx requests a delay or change in the Study that materially
affects the progress of the Study.
(c) The progress of the Study is delayed due to causes customarily
considered as force majeure, including fire, strike, war, embargo, delays
in transportation, inability to obtain necessary supplies, or the act of
any regulatory or governmental authority.
6.2.2. Other Services
ICON shall also assist Xxxxxxxxxx in any other way Carrington deems
necessary or appropriate to coordinate with Monitored Sites in their
completion of the Study and submission of Study data on a timely and
satisfactory basis. Should these services require an allocation of staff
in addition to that provided for under other Sections of this Agreement,
or the purchase of materials by ICON, Xxxxxxxxxx shall pay such charges
as agreed to in advance.
6.2.3 Payment for Premature Termination
(a) In the event this Agreement is terminated before conclusion of the
Study for any reason, ICON shall use its best efforts to reduce the cost
and/or loss incurred or suffered by Xxxxxxxxxx as a result of such
premature termination.
(b) In the event that this Agreement is terminated before conclusion of
the Study by reason of any willful default by ICON, ICON shall repay to
Xxxxxxxxxx all payments made under this Agreement.
In the event this Agreement is terminated prior to conclusion of the
Study for any reason other than ICON's default, insolvency or bankruptcy,
then in lieu of amounts otherwise payable under Section 6.1 Xxxxxxxxxx
shall pay ICON in the amount of:
$US($147,468)(One hundred forty seven thousand, four hundred and sixty
eight US dollars)
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6.3 Address for Payments
All payments required to be made to ICON by Xxxxxxxxxx shall be in the
form of electronic funds or checks drawn on a U.S. bank, payable to ICON,
whichever is faster. Checks should be mailed to:
ICON Clinical Research, Inc.
000 Xxxx Xxxxxxxxxx Xxxx
Xxxxx 000
Xxxxxxxxxx, XX 00000
Electronic funds transfer should be made to:
CoreStates Bank
Trappe Center Branch Office
FC 3-6-1-1
000 Xxxx Xxxx Xxxxxx
Xxxxxx, XX 00000-0000
For Credit to:ICON, Inc.
A/C No.:5917-1453
Sort Code No.:0310-00011
SECTION 7
CONFIDENTIALITY, PUBLICATIONS, INVENTIONS, NON-COMPETITION
7.1 Confidentiality. All information received by ICON from Xxxxxxxxxx
and all data and other information developed with respect to Xxxxxxxxxx
or the study by ICON or its employees, agents, subcontractors or
affiliates, is and shall be considered throughout the term of this
Agreement and thereafter as Confidential Information, except for
information which:
(a) at the time of disclosure thereof is or becomes part of the public
domain through no breach or fault of ICON or its employees, agents,
subcontractors, or affiliates. For the purpose of this Agreement,
"affiliate" shall mean any company, partnership or other entity which
directly or indirectly controls, is controlled by, or is under control
with, ICON, "control" meaning an ownership of 50% or more of any issued
share capital or the legal power to direct or cause the direction of the
general management and policies of ICON.
(b) at the time of disclosure thereof by Xxxxxxxxxx, is in ICON's lawful
possession as evidenced by ICON's competent written records;
8
ICON receives from a third party who has the right to disclose the same
and who did not obtain such information in violation of Xxxxxxxxxx'x
rights;
ICON shall hold such Confidential Information in strict confidence and
shall only disclose Confidential Information to its employees, agents,
and representatives including but not limited to clinical investigators
and other personnel at all Monitored Sites on a need-to-know basis. ICON
shall ensure that such employees, agents and representatives shall be
bound and obligated by identical provisions of confidentiality as is ICON
hereunder. ICON shall not disclose to any third party any of the
Confidential Information without specific prior written authorization
from Xxxxxxxxxx with respect to such disclosure.
7.2 Papers Utilizing Study Data. ICON agrees, on behalf of itself, its
employees, agents, subcontractors, and affiliates, not to publish or
present the results of the Study without the prior written consent of
Xxxxxxxxxx, which consent is within Xxxxxxxxxx'x discretion. Before any
such paper or abstract is submitted for publication or any such
presentation or announcement is made, a complete copy of such paper or
abstract, or a transcript of such presentation or announcement, shall be
given to Xxxxxxxxxx at least 60 (sixty) days prior to submission,
presentation or announcement thereof to any third party. Xxxxxxxxxx shall
review any such paper, abstract or transcript and give its comments to
the author and ICON promptly. ICON shall comply with Xxxxxxxxxx'x request
to delete reference to Xxxxxxxxxx'x Confidential Information in any such
paper, abstract, presentation or announcement, and to withhold
publication, presentation or announcement of same for an additional 60
(sixty) days in order to permit Xxxxxxxxxx to obtain patent or other
proprietary protection, if Carrington deems it necessary or appropriate.
Any publication approved by Xxxxxxxxxx and published by Xxxxxxxxxx or by
one or more of the study investigators should incorporate at least one
named co-author from ICON.
7.3 Inventions, etc. The results of the Study and all documentation
generated therein (including CRFs and all or any intellectual property
rights (including any copyrights therein)) and any inventions or
discoveries (whether or not patentable), innovations, suggestions, ideas
and reports made or developed by ICON as a result of performing services
hereunder shall be promptly disclosed to Xxxxxxxxxx and shall be sole
property of Xxxxxxxxxx Upon Xxxxxxxxxx'x request and at Xxxxxxxxxx'x
expense, ICON shall execute such documents and take such actions as
Carrington deems necessary or appropriate to obtain patent or other
proprietary protection in Xxxxxxxxxx'x name concerning any of the
foregoing. The obligations of this Section 7.3 shall apply to ICON's
employees, agents and representatives involved in the services to be
performed by it hereunder and ICON agrees to cause such parties to
execute agreements ensuring compliance with this section.
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SECTION 8
INDEMNIFICATION
8.1 Indemnification by Xxxxxxxxxx
Subject to Section 8.2 below Xxxxxxxxxx shall indemnify ICON, its
employees, affiliates, members of the IRB and clinical investigators (the
"Indemnitees"), for the cost of defense and compensatory damages awarded,
if any, arising out of any claim or lawsuit resulting from bodily injury
caused by the administration of Study Drug supplied by Xxxxxxxxxx for use
in the Study, provided that:
(a)emdemnitees have used the Study Drug in accordance with accepted
medical practices and in compliance with the Protocol and all
precautions, indications and other instructions furnished by Xxxxxxxxxx;
and
(b)such bodily injury was not in any way caused by the negligence or
wilful misconduct of Indemnitees.
8.2 Indemnification by ICON.
ICON shall indemnify Xxxxxxxxxx, its employees, affiliates, and agents
for the cost of defense and compensatory damages awarded, if any, arising
out of any claim or lawsuit resulting from bodily injury caused by the
negligence or wilful misconduct of ICON, its employees, affiliates or
agents, or the failure of ICON, its affiliates, employees or agents, to
perform in accordance with the terms and conditions of this Agreement or
in compliance with accepted medical practices or any precautions,
indications or other instructions furnished by Xxxxxxxxxx.
SECTION 9
ADVERSE EVENTS
9.1 Adverse Events. A Monitored Site shall have the right to provide
reasonable and customary treatment to any person involved in the Study
who exhibits symptoms of an adverse event. Xxxxxxxxxx shall pay for all
necessary diagnostic assessment and medical treatment for any patient
injury or illness directly resulting from administration of the Study
Drug hereunder, when the Study Drug is used in accordance with the
Protocol. If in the opinion of the clinical investigator and Xxxxxxxxxx,
the suspected adverse event proves to be non-Study Drug related,
Xxxxxxxxxx shall pay only the reasonable and customary costs associated
with the diagnosis. Xxxxxxxxxx'x agreement to pay for the foregoing
expenses is without prejudice to its right to seek financial
reimbursement from such Monitored Site or ICON or in the event injury or
illness results from the negligence or wilful misconduct of such
Monitored Site or ICON or their respective employees or agents.
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9.2 Notification. ICON shall report all significant adverse events,
including but not limited to those that are serious and unexpected, to
Xxxxxxxxxx and if appropriate to the IRB. All serious adverse events
shall be reported by ICON to Xxxxxxxxxx orally within 24 hours of ICON
being so notified, and then promptly thereafter followed up with written
documentation. Xxxxxxxxxx shall also notify the Regulatory Agency of
serious adverse events or reactions after it has received clinical
investigator reports thereof. Adverse events will also be recorded on
CRFs.
SECTION 10
MISCELLANEOUS
10.1 Modification and waiver. No modification of this Agreement shall be
deemed effective unless in writing and signed by each of the parties
hereto, and no waiver of any right set forth herein shall be deemed
effective unless in writing and signed by the party against whom
enforcement of the waiver is sought.
10.2 Integration of Agreement. This Agreement represents the entire
Agreement between the parties and supersedes all prior negotiations,
representations or agreements, written or oral, regarding the Study. In
the event of any conflict between the terms and conditions of this
Agreement and those of the Protocol, the terms and conditions of this
Agreement shall control.
10.3 Descriptive Headings. The descriptive headings of the sections of
this Agreement are inserted for convenience only and shall not control or
affect the meaning or construction of any provision hereof.
10.4 Applicable Law. This agreement shall be governed and construed in
accordance with the laws of the the state of Texas.
10.5 Independent Contractor. ICON's status hereunder is that of an
independent contractor and ICON has no authority to bind or act on behalf
of Xxxxxxxxxx except as otherwise specifically stated herein.
10.6 Use of Names. Each party, on behalf of itself, its employees and
agents, agrees not to use the name of the other party or its employees or
agents in any publication, promotional material or other written or oral
statement for public distribution, relative to the subject matter or
existence of this Agreement, except as otherwise required by law or as
permitted under Section 7.2 of this Agreement or previously consented to
in writing by the other party.
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10.7 Notices. All notices hereunder shall be in writing as follows:
If to ICON address to:ICON Clinical Research, Inc.
000 Xxxx Xxxxxxxxxx Xxxx
Xxxxx 000
Xxxxxxxxxx, XX 00000
If to Xxxxxxxxxx address to:
Xxxxxxxxxx Laboratories, Inc.
0000 Xxxx Xxxxxxxx Xxxxxxxxx
Xxxxxx, XX 00000-0000
Or to such other persons or addresses as either party may request by
notice given as set forth above. Notices shall be deemed given at the
time of personal delivery or 3 (three) business days after the date
mailed in the manner set forth in this Section.
10.8 Third Parties; Assignment. ICON warrants and represents that
proceeding and performing hereunder is not inconsistent with any
contractual or other legal obligations it has and shall not be
inconsistent with any contractual or other legal obligations it may
hereafter have. ICON may not assign this agreement or its obligations
hereunder, nor may it contract with third parties to perform any of its
obligations hereunder, without Xxxxxxxxxx'x prior written consent.
10.9 Severability. If any of the provisions of, or a portion of any of
the provisions of, this Agreement is held to be unenforceable or invalid
by a court of competent jurisdiction, the validity and enforceability of
the enforceable portion of any such provision and/or the remaining
provisions shall not be affected thereby.
10.10 Counterparts. This agreement shall be executed in 2 counterparts,
each of which shall be deemed an original, but both of which together
shall constitute one and the same instrument.
IN WITNESS WHEREOF, the undersigned by their duly authorized
representatives have executed this Agreement as of the Effective Date.
Xxxxxxxxxx Laboratories, Inc. ICON Clinical Research, Inc.
By:________________________ By:_________________________
Xxxxxxx X. Xxxxxx, M.D.Xxxxxxx X. Xxxx
Title: President and CEO Title: Secretary/Treasurer
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Exhibit A Fixed Fee Estimate and Assumptions
STUDY FEE ESTIMATE
Sponcer: Xxxxxxxxxx Laboratories
Study: Protocol 9009:Placebo-Controlled Study of Oral
Acemannan in Ulcerative Colitis
Date: September 9, 1996
-----------------------------------------------------------------------
US Dollars
1. Investigator Grants:
Investigator Fees: 280 patients@$3,500 per patient $980,000
2. IRB Approval:
3. Project Team (12 months) *
Project Manager 62,058
CRAs 369,240
Clinical Research Assistant 70,524
Clinical Data Auditor 25,776
Medical Reviewer 28,644
Quality Assurance 33,610
Secretarial Personnel 21,450
-------
Subtotal 611,320
4. Travel Costs *
Site Evaluations 35 visits 42,000
Initiation 30 visits 36,000
Monitoring 150 visits 187,920
QA 6 visits 7,920
Close Out 30 visits 39,600
-------
Subtoal 313,440
5. Communications with the sites: * 29,700
6. Investigator Meeting (83 attendees)
2 delegates per site (70), 7 ICON & 6 Xxxxxxxxxx
Personnel 108,000
7. Clinical Grant Administration * 16,500
8. Overhead 58,258
* Overhead charge is applied to these items
--------
GRAND TOTAL $2,123,218
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STUDY FEE ESTIMATE
Sponcer: Xxxxxxxxxx Laboratories
Study: Protocol 9009:Placebo-Controlled Study of Oral
Acemannan in Ulcerative Colitis
Date: September 9, 1996
-----------------------------------------------------------------------
ASSUMPTIONS
ICON has based its fixed fee cost estimate on an 12-month study
period, including a 5-month patient enrollment period.
1.Per Protocol 9009, 280 patients will be enrolled.
2.Visits include 1 placement to 35 sites and 1 initiation visit, 5
monitoring visits, and 1 close-out visit to 30 sites (8 visits/site).
Six sites will undergo a QA audit.
3.Costs for running off-site meetings have not been included.
4.Cost does not include drug distribution.
5.CRF printing costs have not been included.
6.Xxxxxxxxxx Labs will be responsible for subcontracting the central
laboratory (SciCor).
7.Investigator fee payments will be prorated according to visits
completed as follows:
Visit # 1(Screen) 2 3 Total
Cost per Visit $1610.00 $460.00 $1430.00 $3500.00
8.All courier services will be paid by Xxxxxxxxxx on a pass-through
basis. The main courier will be UPS. UPS charges will be charged
directly to Xxxxxxxxxx'x UPS account number. Xxxxxxxxxx also agrees
that, at the discretion of the ICON Clinical Project Manager, FedEx may
be used to expedite shipments as needed.
9.ICON will use the following travel policy during the conduct of the
study:
A. Documentation. Retain receipts for all amounts in excess of $25.
B. Airfare. Xxxxxxxxxx Laboratories will reimburse ICON for airfare at
actual cost, but not greater than economy or coach rates unless
Xxxxxxxxxx Laboratories has provided prior approval.
C. Hotels. ICON will put forth its best efforts to reserve hotel rooms
at reasonable business travel rates.
D. Rental Cars. ICON has negotiated a special rate with Avis. Where
available, ICON staff will rent a compact class car or smaller.
E. Meal Reimbursement. Meals will be reimbursed at actual cost, but in
no case will reimbursement total more than $65 per day. The $65 per day
rate cannot be "carried" from day to day. Meal reimbursement will be
tallied separately on each expense summary.
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F. Sundries and Incidentals. Ordinarily, it is expected that
reimbursements for sundries and incidentals (for example, toiletries,
batteries, passports) should not be necessary. Incidental expenses of a
personal nature will generally not be reimbursable by Xxxxxxxxxx
Laboratories. An exception is reasonable laundry expenses, which will be
reimbursed by Xxxxxxxxxx Laboratories when ICON staff travel for greater
than three consecutive days away from home on Xxxxxxxxxx
Laboratories-related business only.
G. Tipping Tipping should follow local customs for business
travel(approximately 15%).
H.Telephone. One personal long distance call home per day of reasonable
duration will be reimbursable. A telephone credit card will be used
where possible to avoid hotel telephone surcharges.
I.Entertainment. Shows, movies, video rentals, magazines and newspapers
are not reimbursable.
Exhibit B Payment Schedule*
Payment Schedule
Xxxxxxxxxx Laboratories: Protocol 9009; Ulcerative Colitis
Monthly
Payment No. 1996 Installment Description Total
---------- ---- ----------- -------------------------- --------
1** Sep $212,322 10% up-front $212,000
2 Oct 212,322 first patient enrolled 212,322
3 Nov 212,322 patients 2-70 enrolled 212,322
4 Dec 212,322 patients 71-140 enrolled 212,322
1997
5 Jan 212,322 patients 141-210 enrolled 212,322
6 Feb 212,322 patients 211-280 enrolled 212,322
7 Mar 212,322 patients 1-70 completed 212,322
8 Apr 212,322 patients 71-140 completed 212,322
9 May 212,322 patients 141-210 completed 212,322
10 Jun 212,320 10% final payment 212,320
Total $2,123,218 $2,123,218
* Each payemnt shall be due and payable within thirty (30) days of
receipt
of the invoice by Xxxxxxxxxx Laboratories.
** None-refundable start-up payment.
*** Final payment to be paid upon ICON's completion of all services
provided For in this Agreement and Xxxxxxxxxx'x receipt of all study
documents, including resolution of all queries generated from
Xxxxxxxxxx'x internal audit of the case report.
Exhibit C
Protocol
15
