[LETTERHEAD OF COVANCE]
Covance Clinical Research Unit Inc.
Madison, WI
MASTER CLINICAL DEVELOPMENT SERVICES AGREEMENT
This Clinical Development Services Agreement dated as of 1 December 1997, is
between - Discovery Laboratories, Inc. ("Sponsor") and Covance Clinical Research
Unit ("Covance").
1. Protocol/Pricing Schedule
a. Covance will perform a study or studies ("Study") for Sponsor in
accordance with a detailed protocol document ("Protocol") that will
be provided by Sponsor or prepared by Covance with the Sponsor's
input and approved by Sponsor. The Protocol will specify the Study
design, objectives, number of subjects, measurements, estimated
duration of the Study, and all other relevant matters. Covance will
perform its services for the Sponsor in connection with the Study on
the terms specified in the pricing schedule attached hereto as
Exhibit A (the "Pricing Schedule"). The Pricing Schedule will set
forth the pricing and payment terms for the Study and is deemed a
part of this Agreement and is incorporated herein by reference.
b. If requested by Sponsor, Covance will consult with Sponsor to assist
Sponsor in developing the Study design in a manner consistent with
current regulatory guidelines. Covance does not warrant the Protocol
or Study design, or that the Study results, will satisfy the
requirements of any regulatory agencies at the time of submission of
study results to such agencies.
2. Study Materials
Sponsor will provide Covance with sufficient amounts of drug with which to
perform the Study, as well as such sufficient and comprehensive data as
may be required by Covance concerning the stability of the test material
end storage and safety requirements.
3. Principal Investigator
Covance will appoint a "Principal Investigator" to be responsible for the
Study.
[LETTERHEAD OF COVANCE]
4. Compliance with Government Regulations
a. Covance will perform the Study in accordance with the Protocol.
Covance will also comply in all material respects with all current
government regulatory requirements concerning Good Clinical
Practices as considered to be appropriate at the time of study
initiation.
b. Should such government regulatory requirements be changed, Covance
will make every reasonable effort to satisfy the new requirements.
In the event that compliance with such new regulatory requirements
necessitates a change in the Protocol for the Study, Covance will
submit to Sponsor a revised Pricing Schedule for Sponsor's
acceptance prior to making any changes in the Protocol or Study.
5. Sponsor Visits to Facilities
Sponsor's representatives may visit Covance's clinic with reasonable
frequency, upon reasonable notice, during normal business hours to observe
the progress of the Study. Covance will assist Sponsor in scheduling such
visits.
6. Confidential Information/Legal Proceedings
a. Covance will not disclose to any business or institution not
affiliated with Covance, without Sponsor's written permission, any
information pertaining to Sponsor's Study or this Agreement unless
such disclosure is required by any law, rule, regulation, order,
decision, decree, subpoena, or other legal process ("Law").
Disclosures to Institutional Review Boards are understood to be
required by Law. If such disclosure is requested by Law, Covance
will notify sponsor of this request promptly, and, if possible,
prior to any disclosure to permit Sponsor to oppose such disclosure
by appropriate legal action.
b. If Covance shall be obliged to provide, assistance, including
testimony, or records regarding any Sponsor Study in any legal or
administrative proceeding, then Sponsor shall reimburse Covance its
out-of-pocket costs and an hourly fee for its employees or
representatives.
7. Work Product
a. All reports, including case report forms, will be prepared in
Covance's standard format unless otherwise specified in the
Protocol.
Master Clinical Development Services Agreement
[LETTERHEAD OF COVANCE]
b. Raw data in paper, magnetic or other form, will be retained by
Covance in compliance with regulatory requirements and the study
price includes the cost of meeting these requirements. Upon
expiration of any regulatory requirements to maintain such data or
after 15 years, whichever is later, Sponsor shall upon Covance's
request direct that such data be delivered to Sponsor or be retained
by Covance for a standard storage fee and Covance will comply with
such direction.
8. Test Article
Upon completion of the Study, unless required by Law and so notified by
the Sponsor in writing, any remaining samples of test or control materials
will be returned to Sponsor, at Sponsor's expense, for retention in
compliance with regulatory requirements. If so notified by the Sponsor,
Covance will retain samples of test or control materials for a standard
storage fee.
9. Inventions and Patents
At Sponsor's request, Covance will assign to Sponsor the rights to any
patentable invention discovered by Covance's employees exclusively as a
result of performing Sponsor's Study and pertaining to the Test Article,
provided Sponsor requests such assignment within 90 days of notification
of such invention and further provided that if such invention relates to
testing methods or processes, Sponsor shall grant to Covance and its
affiliates a [***] to practice such methods or processes in perpetuity. If
Sponsor requests and at Sponsor's expense, Covance will provide Sponsor
with reasonable assistance to obtain patents covering such inventions.
10. Independent Contractor
Covance shall perform the Study as an independent contractor and shall
have complete and exclusive control over its employees and agents.
11. Insurance
Covance shall secure and maintain in full force and effect throughout the
performance of the Study insurance coverage for (a) Workmen's
Compensation, (b) General Liability, and (c) Automobile Liability in
amounts appropriate to the conduct of Covance's business in Covance's sole
and exclusive judgement. Certificates evidencing such insurance will be
made available for examination upon request by Sponsor.
[***] -- Confidential treatment requested.
Master Clinical Development Services Agreement
[LETTERHEAD OF COVANCE]
12. Remedies/Indemnities
a. In the event of a material error by Covance in the performance of
the Study that renders the Study invalid, Covance's sole obligation
to Sponsor shall be for Covance, at its option, to either (a) repeat
the Study at Covance's own cost, or (b) refund to Sponsor the
contract price paid. UNDER NO CIRCUMSTANCES SHALL SPONSOR BE
ENTITLED TO INDIRECT, INCIDENTAL OR CONSEQUENTIAL DAMAGES FOR
COVANCE'S NONPERFORMANCE OR IMPROPER PERFORMANCE OF ITS OBLIGATIONS
UNDER THIS AGREEMENT, STUDY, OR PROTOCOL.
b. Covance shall indemnify Sponsor from any claims or expense incurred
by Sponsor arising solely out of Covance's willful or negligent acts
giving rise to any personal injury, death, or property damage
occurring during the conduct of the Study. Such indemnity shall not
extend to any loss or expense resulting from any claim arising out
of Sponsor's use or marketing of any substance that is the subject
of the Study.
c. Sponsor shall indemnify Covance and its affiliates and their
respective officers, directors, employees, agents and independent
contractors, (including the University of Wisconsin-Madison and
University of Wisconsin-Madison personnel) the "Covance GROUP" from
any loss, damage, cost or expense (including reasonable attorney's
fees) (collectively, a "Loss") arising from any claim, demand,
assessment, action, suit or proceeding (a "Claim") as a result of
(i) Covance's performance of or involvement with the Study or its
obligations under this Agreement or the Protocol or (ii) Sponsor's
tortuous conduct or inaction provided that neither willful nor
negligent acts by the Covance GROUP were responsible for such Loss.
In addition, and without limiting the foregoing, Sponsor shall
indemnify Covance GROUP from any Loss from any Claim arising out of
Sponsor's use or marketing of any substance tested by Covance.
d. Upon receipt of notice of any Claim which may give rise to a right
of indemnity from the other party hereto, the party seeking
indemnification (the "Indemnified Party") shall give written notice
thereof to the other party, (the Indemnifying Party") with a claim
for indemnity. Such Claim for indemnity shall indicate the nature of
the Claim and the basis therefore. Promptly after a Claim is made
for which the Indemnified Party seeks indemnity, the Indemnified
Party shall permit the Indemnifying Party, at its option and
expense, to assume the complete defense of such Claim, provided that
(i) the Indemnified Party will have the right to participate in the
defense of any such Claim at its own cost and expense, (ii) the
Indemnifying Party will conduct the defense of any Claim with due
regard for the business interests and potential related liabilities
of the Indemnified Party and (iii)
Master Clinical Development Service Agreement
[LETTERHEAD OF COVANCE]
the Indemnifying Party will, prior to making any settlement, consult
with the Indemnified Party as to the terms of such settlement. The
Indemnified Party shall have the right, at its election, to release
and hold harmless the Indemnifying Party from its obligations
hereunder with respect to such Claim and assume the complete defense
of the same in return for payment by the Indemnifying Party to the
Indemnified Party of the amount of the Indemnifying Party's
settlement offer. The indemnifying Party will not, in defense of any
such Claim, except with the consent of the Indemnified Party,
consent to the 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 the Indemnified Party of a release
from all liability in respect thereof. After notice to the
Indemnified Party of the Indemnifying Party's election to assume the
defense of such Claim, the Indemnifying Party shall be liable to the
Indemnified Party for such legal or other expenses subsequently
incurred by the Indemnified Party in connection with the defense
thereof at the request of the Indemnifying Party. As to those Claims
with respect to which the Indemnifying Party does not elect to
assume control of the defense, the Indemnified Party will afford the
Indemnifying Party an opportunity to participate in such defense, as
the Indemnifying Party's own cost and expense, and will not settle
or otherwise dispose of any of the same without the consent of the
Indemnifying Party.
13. Generic Drug Enforcement Act of 1992
Covance Clinical Research Unit Inc.: (a) represents that it has never
been, and its employees have never been debarred or convicted of a crime
for which a person can be debarred under 21 USC Sec. 335a ("335a"); nor
threatened to be debarred or indicted for a crime or otherwise engaged in
conduct for which a person can be debarred under 335a; (b) agrees that it
will promptly notify Sponsor in the event of any such debarment,
conviction, threat or indictment occurring during the term of this
Agreement or three (3) years following its termination or expiration; and
(c) agrees not to employ any person in connection with any of the work to
be performed under this Agreement who has been debarred or convicted of a
crime for which a person can be debarred.
14. Force Majeure
Either party shall be excused from performing its obligations under this
Agreement if its performance is delayed or prevented by any cause beyond
such party's control, including, without limitation, acts of God, fire,
explosion, weather, disease, war, insurrection, civil strife, riots,
government action, or power failure. Performance shall be excused only to
the extent of and during the reasonable continuance of such disability.
Any deadline or time for performance specified in the Protocol that falls
due during or subsequent to the occurrence of any of the disabilities
referred to herein shall be automatically extended for a period of time
equal to the period of such disability.
Master Clinical Development Services Agreement
[LETTERHEAD OF COVANCE]
Covance will notify Sponsor as soon as practicable if, by reason of any of
the disabilities referred to herein, Covance is unable to meet any
deadline or time for performance specified in the Protocol. In the event
that any part of the Study is rendered invalid as a result of such
disability, Covance will, upon written request from Sponsor and at
Sponsor's sole cost and expense, repeat that part of the Study affected by
the disability.
15. Allocation of Resources
If delays in performance of the Study are experienced because of Sponsor's
inability to supply Covance with materials or information required to
perform the Study, Covance reserves the right to reallocate resources
otherwise reserved for performance of the Study without incurring
liability to Sponsor.
16. Use of Names
Sponsor shall not use Covance's name or the names of Covance's employees
in any advertising or sales promotional material or in any publication
without prior written permission of Covance. Covance will not use
Sponsor's name or the names of Sponsor's employees in any advertising or
sales promotional material or in any publication without prior written
permission of the Sponsor.
17. Termination
a. Sponsor shall have the right at any time to terminate any Study
prior to completion by giving written notice to Covance. In the
event of termination by the Sponsor, Sponsor shall pay Covance upon
receipt of Covance's invoice the amount specified as set forth in
Exhibit A.
b. Covance shall have the right to terminate the Study prior to
completion for any of the following reasons:
(1) Sponsor's breach of the Agreement.
(2) Covance's good faith determination that it is not safe to
continue the Study.
In the event of termination by Covance due to (1) and/or (2) above,
Sponsor shall pay Covance upon receipt of Covance's invoice the
amount specified as set forth in Exhibit A.
c. The termination of this Agreement shall not relieve either party of
its obligation to the other in respect of (i) maintaining the
confidentiality of information, (ii)
Master Clinical Development Services Agreement
[LETTERHEAD OF COVANCE]
obtaining consents for advertising purposes and publications, (iii)
indemnification, and (iv) compensation for services performed.
18. Assignment
Covance shall not assign the clinic portion of this Agreement without the
prior written consent of Sponsor, which consent shall not be unreasonably
withheld.
19. Notice
All notices given under this Agreement shall be in writing and shall be
delivered personally, sent by telegram, telefax, or mailed to the parties
at the addresses set forth below, or such other addresses as the parties
may designate in writing.
20. Amendments
Any amendments or revisions to this Agreement, the Pricing Schedule or the
Protocol must be proposed in writing by either party and accepted in
writing by the other party before they shall become effective and binding.
21. Waiver
No waiver of any term, provision, or condition of this Agreement, the
Pricing Schedule or the Protocol whether by conduct or otherwise in any
one or more instances shall be deemed to be or construed as a further or
continuing waiver of any such term, provision, or condition or of any
other term, provision, or condition of this Agreement.
22. Arbitration
a. All disputes between the parties which are not resolved by means of
direct negotiations between them and which arise out of this
Agreement, the Pricing Schedule or the Protocol shall be finally
settled by arbitration in accordance with this Section. The
arbitration shall be held in or around Madison, Wisconsin as
determined by Covance, and shall be conducted in accordance with the
rules of the American Arbitration Association by two arbitrators
appointed, one by each party to this Agreement. If the arbitrators
appointed cannot agree on the resolution of the dispute within 60
days after the dispute is submitted to them, they shall thereupon
appoint a third arbitrator, and if they fail to agree upon a third
arbitrator within 30
Master Clinical Development Services Agreement
[LETTERHEAD OF COVANCE]
days after a deadlock is declared by either arbitrator, a third
arbitrator will be appointed by the American Arbitration Association
upon the request of either such arbitrator.
b. Any decision by the third arbitrator and either one of the other
arbitrators shall be binding upon the parties and may be entered as
a final judgement in any court having jurisdiction. The arbitration
shall be conducted completely in the English language. The cost of
any arbitration proceeding shall be borne by the parties as the
arbitrators shall determine if the parties have not otherwise
agreed. The arbitrators shall render their final decision in writing
in English to the parties, which decision shall explain the reasons
therefor.
23. Entirety
This Agreement, together with the Pricing Schedule and the Protocol, is
the entire understanding between Sponsor and Covance. It replaces,
supersedes and renders void any and all predecessor and contemporaneous
negotiations, agreements, representations, understandings and commitments
between the parties.
24. Governing Law
This Agreement is a Wisconsin contract. It shall be governed, construed,
and interpreted in accordance with the laws of Wisconsin.
In witness whereof, the parties have executed this Agreement.
DISCOVERY LABORATORIES, INC.
By: /s/ Xxxxx X. Xxxxxxxxx 12/04/97
---------------------------- -------------
Date
Title: Vice President
-------------------------
COVANCE CLINICAL RESEARCH UNIT
By: /s/ Xxxxxxx X. Xxxxxx 12-1-97
------------------------ -------------
Authorized Signature Date
Xxxxxxx X. Xxxxxx
Title: Contracts Administrator/
Senior Client Manager
Master Clinical Development Services Agreement
Covance Clinical Research Unit
EXHIBIT A
PRICING SCHEDULE
Pricing Schedule dated as of 1 December 1997, is between Client ("Sponsor") and
Covance Clinical Research Unit ("Covance").
WITNESSETH
WHEREAS, Sponsor and Covance have entered into that certain Master Clinical
Development Services Agreement dated as of 1 December 1997, (as amended or
modified from time to time, the "Master Clinical Development Services
Agreement"; terms defined therein an used herein as defined therein unless
otherwise defined herein);
WHEREAS, Covance has agreed to perform the Study for the Sponsor on the terms of
the Clinical Development Services Agreement, the Protocol and this Pricing
Schedule;
WHEREAS, this Pricing Schedule is the Pricing Schedule referred to in the
Clinical Development Services Agreement;
WHEREAS, Covance will perform such Study on the price specified in this Pricing
Schedule.
NOW, THEREFORE, the Sponsor and Covance hereby agree to the following price and
payment schedule in connection with Study and Protocol identified below.
STUDY NO.: 8475 PROTOCOL NO.: ST-630-01A
TITLE: A Phase IA, Double-Blind, Placebo-Controlled, Rising
Single-and Multiple-Dose, Safety, Tolerance and
Pharmacokinetic Study of ST-630 Softgel Capsules Administered
at 0.0625, 0.125, 0.25, 0.375, or 0.5 (mu)g in Normal Healthy,
Volunteers
PRICE: $393,554
PAYMENT SCHEDULE:
At signing of the Agreement [***]
Following successful completion of Group A [***]
Following successful completion of Group B [***]
Following successful completion of Group C [***]
Following successful completion of Group D [***]
Master Clinical Development Services Agreement
[***] - Confidential treatment requested.
Following successful completion of Group E [***]
Following completion and approval of the CTR [***]
Price quoted is predicated on Covance receiving all necessary test material and
other data required to conduct the Study outlined in this proposal within 30
days of Covance's signing of this Pricing Schedule.
Termination Terms:
If the study is terminated after initiation but prior to completion of 5 groups,
the following fees will be charged:
[***]
Postponement Terms:
If the study is postponed within 30 days of 4 December 1997, Sponsor is
responsible for payment of all variable costs incurred to date, as well as, any
costs associated with additional advertising, recruiting, and screening efforts
to ensure enrollment of a full panel plus a fee of 5% of the full study price.
IN WITNESS WHEREOF, the undersigned have executed this Pricing Schedule as of
the date first above written.
Discovery Laboratories, Inc. Covance Clinical Research Unit
By: /s/ Xxxxx X. Xxxxxxxxx By: /s/ Xxxxxxx X. Xxxxxx
---------------------------- -------------------------------
Authorized Signature
Name: XXXXX X. XXXXXXXXX Title: Contract Administrator/
-------------------------- ----------------------------
Senior Client Manager
Title: Vice President
-------------------------
Master Clinical Development Services Agreement
[***] - Confidential treatment requested.
Budget
Prepared for Discovery Laboratories, Inc.
by Covance Clinical Research Unit Inc.
Protocol No. ST-630-01A - Study No. 8475
30 Volunteers, 5 Groups of 6
1 December 1997
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FIXED COST FOR STUDY TOTAL
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Advertising [***]
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Recruiting/Screening [***]
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IRB [***]
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Project Management [***]
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Quality Assurance [***]
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Clinical Confinement (Includes all meals) 30 Volunteers x 5 Nights [***]
15 Alternates x 1 Night
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State Unemployment Insurance [***]
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Archiving [***]
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Supplies and Shipping [***]
--------------------------------------------------------------------------------
FIXED COSTS PER GROUP (X5)
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Physician [***] [***]
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Clinical Procedures [***] [***]
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Data Entry [***] [***]
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Report Writing [***] [***]
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VARIABLE COSTS
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Volunteer Stipends - On-Study [***]
--------------------------------------------------------------------------------
[***] x 30 Volunteers
[***] x 15 Alternates
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Labs and ECG [***]
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Screening 75 Volunteers x 1 Timepoint
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On-Study 30 Volunteers x Study Timepoints
15 Alternates x 1 Timepoint
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Clinical Cost Total [***]
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Data Management Costs [***]
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Costs Incurred for Protocol and IND Development [***]
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Monitoring [***]
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Total Study Cost [***]
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Price quoted is contingent on final protocol and is valid for 30 days.
Additional medical expenses (i.e., consultations) will be billed to the Sponsor
on a case by case basis.
[***] - Confidential treatment requested.
