Exhibit 10.17
[NOTE: CERTAIN PORTIONS OF THIS DOCUMENT HAVE BEEN MARKED TO INDICATE THAT
CONFIDENTIALITY HAS BEEN REQUESTED FOR THIS CONFIDENTIAL INFORMATION. THE
CONFIDENTIAL PORTIONS HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION.]
SIMBEC
CLINICAL RESEARCH AGREEMENT
This Clinical Research Agreement is made by and between SIMBEC RESEARCH LIMITED
("Simbec"),
A United Kingdom corporation and INSPIRE PHARMACEUTICALS INC. ("Company").
Whereas, Simbec is engaged in the business of performing clinical research
studies;
Whereas, Company is engaged in the development, manufacture, distribution and/or
sale of pharmaceutical
and medical products and desires to retain Simbec's services in conducting the
study entitled [CONFIDENTIAL TREATMENT REQUESTED], in accordance with the terms
and conditions herein;
Now, therefore, in consideration of the mutual covenants herein contained, the
parties agree as follows:
ARTICLE 1 - DEFINITIONS
1.1 "Protocol" - A plan which governs how the study will proceed for a
particular project. A protocol
includes, but is no limited to, a description of how many subjects will be
evaluated and how and what information will be obtained from subjects. A
protocol is identified by the specific protocol or project number.
1.2 "Facilities" -Clinical facility designated in a protocol where subjects
involved in the study receive treatment and where data are collected.
1.3 "Case Report Form (CRF)" - A collection of documents designed specifically
for recording data as required under a protocol. A CRF is created and completed
for each subject involved in the study.
ARTICLE II - ENGAGEMENT OF SIMBEC TO MANAGE THE STUDY; TRANSFER OF
OBLIGATIONS
2.1 Study Protocol
Simbec will review the clinical protocol.
2.2 CRF Development
Simbec will provide Company with paper Case Report Forms (CRFs) for this study.
The CRFs will be printed on NCR paper and the Company will review all drafts and
approve the final version of the CRFs before printing. Similarly, Informed
Consent Forms will be prepared by Simbec and are subject to the Company's
approval.
2.3 Program Database
Simbec agrees to determine necessary requirements, prepare database
specifications, program the database, validate the database prior to data entry,
verify database output after data entry is complete and store the database by
archiving it according to Simbec's business practices. Simbec agrees to provide
Company with a complete copy of the final electronic database in PC SAS (R)
and/or Excel (R) format promptly at the conclusion of the study. Simbec will
perform coding of adverse events using COSTART dictionary.
2.4 Perform Double Data Entry
Simbec agrees to enter manually all information contained in each CRF twice, by
two (2) different individuals, into the study database to compare the two (2)
data sets to ensure that the data entered are identical and to identify and
correct any data entry discrepancies. If the central laboratory does not
provide validated electronic data, Simbec agrees to enter manually data received
on hard copy for the central laboratory twice, by two (2)different individuals,
into a database for the laboratory data, to compare the two (2) data sets to
ensure that the data entered are identical; and to identify and correct any data
entry discrepancies. If any data entry discrepancies require resolution by the
clinical facility, Simbec will prepare and submit data queries to the clinical
facility. Simbec agrees to complete data entry and issue all necessary data
queries to the clinical facility within four (4) weeks of receipt of the final
case report form. Simbec will ensure that database edits are completed and the
database is closed and declared clean within one (1) week after receipt of the
final completed data query from the clinical facility.
2.5 Biostatistical Analysis and Reporting
Simbec will produce a study safety summary within one week of completion of each
study cohort. The safety summary will include:
- Listings of all adverse events recorded for each cohort.
- Listings of all ocular assessments recorded for each cohort.
- A tolerance assessment by the investigating physician.
Simbec will conduct the final analysis of study data according to the
statistical analysis plan based on the protocol developed using SAS and Excel
programs and formulae used in all statistical analysis. Preliminary tables for
Company's review of format and data listings will be provided before the
database has been closed.
2.6 Data Management
Simbec will provide Company with Data Handling Manual or equivalent which will
include computer programming for appropriate data edit checks. Simbec will also
provide Company with CRFs annotated with SAS variable names used in data
management and statistical analysis.
2.7 Communication with the Company
Simbec agrees to conduct liberal, routine communications with Company by
telephone, facsimile, e-mail, or correspondence and will promptly inform Company
of any unusual occurrences in the conduct of the study. In person visits to
Company's facilities are not included in the price estimate for the study and,
if required, will be billed separately at Simbec's hourly rate, plus travel
expenses.
2.8 Laboratory Analysis
Laboratory analysis, subject assessments and reports thereof will be provided as
detailed in the Protocol.
1) Simbec agrees to provide data associated with subject screening; and
2) Simbec agrees to provide the physical examinations of the subjects and
reports thereof as described in the Protocol
2.9 Provide Quality Control
Simbec agrees to perform quality control during the study by conducting quality
reviews according to Simbec's SOPS.
2.10 Additional Reporting, Reports or Audits
If Company requests any additional reporting, reports or audits by Simbec,
Company agrees to pay Simbec its hourly rate for these additional reports,
reporting or audits.
2.11 Regulatory Compliance
The Study will performed by Simbec to Good Laboratory Practice (GLP) and Good
Clinical Practice (GCP) regulations and guidelines as appropriate.
It is understood that Simbec is responsible for obtaining ethics committee
approval, this approval is a pre-requisite to proceeding with the Study.
2.12 Conduct of Study
Simbec agrees to conduct the study in strict accordance with the study protocol
and in compliance with the applicable International Committee of Harmonization
guidelines, United Kingdom Medicines Control Agency guidelines, Good Clinical
Practice and the United States Food and Drug Administration's Code of Federal
Regulations section 21, parts 50 and 56. Simbec agrees to maintain complete
records of the disposition of study drug, including dates and quantities used by
the subjects. Simbec agrees to prepare and maintain complete and accurate case
histories to record all observations and other data pertinent to the study on
each study subject.
2.13 Study Monitoring
During the study period, Simbec will monitor the progress of the Study to
determine whether the study is being conducted in accordance with the provisions
specified herein under Section 2.12 (Conduct of Study). Simbec will conduct a
100%audit of case report form data and communicate changes necessary to correct
and reduce discrepancies and errors. Upon completion of each monitoring visit,
Simbec will provide to Company a written report of the observations of the visit
and the progress of the study.
ARTICLE III - COMPANY'S OBLIGATIONS
3.1 Regulatory Compliance
Company will obtain regulatory approval for the study under the laws of the
United Kingdom.
3.2 CRF Development
Company agrees to consult with and provide any needed information to assist
Simbec with the preparation of a template CRF. Company also agrees to notify
Simbec of its approval of the final CRF template and identify which version of
the, CRF template it has approved.
3.3 CRF Printing
Company agrees to consult with and provide any needed information to assist
Simbec with the preparation of a template CRF. Company also agrees to notify
Simbec of its approval of the final CRF template and identify which version of
the, CRF template it has approved.
3.4 Communication with Simbec
Company agrees to conduct routine communications with Simbec by telephone,
facsimile, email, or correspondence.
3.5 Notify FDA of Serious and Unexpected Adverse Events
The Company agrees that the reporting of all "serious and unexpected adverse
events" to the FDA, as required by the laws of the United States, will be the
sole responsibility of the Company. Simbec will notify Company of each serious
or unexpected adverse event within 24 hours of its knowledge of the event using
the Serious Adverse Event Report form provided by the Company.
3.6 Study Monitoring and/or Site Audits
During the study period, Company may monitor the progress of the Study to
determine whether the study is being conducted in accordance with the provisions
specified herein under Section 2.12 (Conduct of Study). Access to subject
medical records and study documentation will be necessary for monitoring and/or
site auditing purposes. Simbec's records and medical information gathered
during this study will be reviewed by representatives of Company and may also be
disclosed to the appropriate regulatory authorities, including the United States
Food and Drug Association and the Local Research Ethics Committee.
3.7 Pay Simbec for its Services and Total Costs of the Study
Company agrees to pay Simbec for all of Simbec's work on and services for the
study and to pay all of the total costs for the study as specified in this
agreement and according to the provisions below:
3.7.a Price Estimate for the Study
Company understands and hereby acknowledges that Exhibit 1 attached to this
agreement is a list of specific activities for the study and a price estimate
for each phase of the study which has been created by Simbec. Company
acknowledges that Exhibit 1 is an estimate of the total price of the study.
Simbec agrees that the total cost, as set forth in Exhibit 1, shall not exceed
[CONFIDENTIAL TREATMENT REQUESTED] (excluding VAT and additional charges
detailed in Exhibit 1). Simbec agrees that the invoices submitted to the
Company for the work performed for the study will be fully itemized. In the
event that the study costs exceed the budget set forth in Exhibit 1, Simbec will
notify Company, in writing, to request approval of additional costs.
3.7.b Payment Schedule
Company agrees to pay for actual work on and services for the study as outlined
in Exhibit I attached hereto in the following manner:
[CONFIDENTIAL TREATMENT REQUESTED]
All payments will be made by Company to Simbec within 30 days of receipt of
invoice.
ARTICLE IV - CONFIDENTIALITY
In consideration for each others' promises and obligations herein, Simbec agrees
that they will not disclose to third parties any non-public information relating
to the study, Company's involvement in the study, any non-public information
about the pharmaceutical products in the study, unless they are required to do
so under the law. Simbec may disclose need-to-know information to a third party
only if they have signed a confidentiality agreement with Simbec that is
equivalent to the agreement that was signed between Simbec and the Company.
Simbec will not publish any information related to the study without prior
written authorization from Company. Simbec will notify company in writing of
any such disclosure at least fifteen (15) days in advance of making such
disclosure.
Exceptions to Confidentiality Provisions
Except as otherwise expressly provided in this agreement, the preceding
paragraph shall not apply to any Confidential Information that Simbec can prove
conclusively (a) has been published in writing and has become, prior to the time
of use or disclosure by Simbec, a part of the public domain other than by reason
of any acts or omissions by possession or knowledge, prior to the time of
Simbec's use or disclosure, by any third party (other than those acting for or
on behalf of Inspire) as a matter of legal right and without restriction on use
or disclosure, (b) was in Simbec's possession or actually known by Simbec prior
to commencement of Simbec's engagement with Inspire, as a matter of legal right
and without restriction on use and disclosure and was not acquired by Simbec or
any of Simbec's employees representatives or
contractors directly or indirectly from Inspire, or (c) was required to be
disclosed by Simbec to comply with applicable laws or regulations or with a
court or administrative order final beyond the possibility of appeal or other
review, provided that Inspire received prior written notice of such disclosure
and that Simbec takes all reasonable and lawful actions to obtain confidential
treatment for such disclosure and, if possible, to minimize the extent of such
disclosure. For purposes of this Agreement, no information shall be deemed to
be in the public domain or in Simbec's possession or knowledge or in the
possession or knowledge of any of Simbec's employees, representatives or
contractors merely because such information is embraced by more general
information in the public domain or in the possession or knowledge of any of the
foregoing.
ARTICLE V - ASSIGNMENT
This Agreement is for the benefit of and shall bind the parties hereto and their
respective successors and assigns provided, however, that neither this Agreement
nor any benefit hereunder may be assigned or otherwise transferred by either
party to any third party without the prior written consent of the other party.
ARTICLE VI - NOTICES
Written communications and any notice which is required to be given hereunder
may be sent by facsimile, e-mail, delivered by courier services or mailed by
prepaid registered post, addressed as follows:
TO: Inspire Pharmaceuticals, Inc.
▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇
▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇
▇▇▇▇▇▇ ▇▇▇▇▇▇ of America
Attention: ▇▇▇ ▇▇▇▇▇ Ph. D.
Facsimile: (▇▇▇) ▇▇▇-▇▇▇▇
TO: Simbec Research Limited
Merthyr Tydfil Industrial Park
Merthyr Tydfil
▇▇▇ ▇▇▇▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇
▇▇▇▇▇▇ ▇▇▇▇▇▇▇
Attention: ▇▇▇▇ ▇▇▇▇▇▇
Facsimile: 011-44-1443-692494
Any written communication or notice so delivered shall be deemed to have been
received by the addressee at the time and date when actually delivered, or in
any event within ten (10) days after posting in the manner provided herein,
provided no postal disruption shall exist. Written documents or notices sent by
wire communications (i.e., facsimile transmission, etc.) shall be deemed to have
been received by the addressee at the time and date when actually sent with
evidence of transmission. The above addresses may be changed at any time by
giving prior written notice.
ARTICLE VII - INTELLECTUAL PROPERTY OWNERHSIP
All Study data collected during the conduct of the Study Protocol shall be and
remain the exclusive property of company. Further, any ideas, know-how,
inventions, processes or other intellectual property which are generated under
or in connection with the Study shall belong to and shall be the sole and
exclusive property of the Company and that Simbec will take all reasonable steps
required to protect such ownership rights for the Company.
ARTICLE VIII - IDEMNIFICATION
8.1 Simbec carries "No Fault" insurance to compensate for injury, accident, ill
health or death caused by participation in clinical trials without regard to
proof of negligence and without delay. Where there is any doubt over causation
the benefit of doubt will be given to the claimant.
8.2 Simbec is indemnified under this policy against professional negligence in
the form of injuries or damages caused by failure to exercise all proper and
reasonable care and skill in the conduct of the Project.
8.3 the Company undertakes to provide product liability cover against injury and
damages arising from the use of products in the Project.
8.4 Simbec shall inform the Company of any claims or legal actions arising out
the Project without delay.
8.5 The obligations of Simbec and the Company under these Indemnity clauses
shall commence at the commencement of the Project and continue in perpetuity.
8.6 Provisions for arbitration in the event of disagreement must be agreed with
Simbec who shall arrange for a Barrister of at least ten years standing to be
appointed by the Royal College of Physicians as arbiter.
8.7 The Company agrees to indemnify and hold harmless Simbec from and against
any loss, damage, cost or expense (including reasonable legal fees) suffered or
incurred by Simbec arising out of any claim or proceedings in respect of death
or bodily injury to Subjects recruited to the Project caused by participation in
the Project unless such loss, damage, cost or expense is due either to the
failure of Simbec to conduct the Project in accordance with the Protocol or is
as a result of Simbec's negligence, willful default, failure or omission whether
by itself, its employees, servants or agents.
8.8 The Company agrees to indemnify and hold harmless the Principal Investigator
from and against any loss, damage, costs or expenses (including reasonable
legal fees) suffered or incurred by the Principal Investigator arising our
of any claims or proceedings in respect of death or bodily injury to Subjects
recruited to the Project caused by participation in the Project unless such
loss, damage, cost or expense is due either to the failure of the Principal
Investigator to conduct the Project in accordance with the Protocol or is as a
result of the Principal Investigator's negligence, willful default, failure or
omission whether by itself, its employees, servants or agents.
8.9 Simbec agrees to indemnify and hold harmless the company from and against
any loss, damage, cost or expense (including reasonable legal fees) suffered or
incurred by the Company arising out of any claims or proceedings in respect of
death or bodily injury to Subjects recruited to the Project caused by Simbec's
negligence, willful default, failure or omission in the conduct of the Project
whether by itself, its employees, servants or agents.
8.10 The foregoing clauses, 8.1-8.9, are in accordance with The Clinical Trial
Compensation Guidelines of The Association of the British Pharmaceutical
Industry.
ARTICLE IX - REFUND PAYMENT FOR ITS SERVICES FOR ERROR AND OMISSION CLAIMS
In the event of errors or omissions caused by the negligence or intentional
misconduct of Simbec that render a study unacceptable to the United States Food
and Drug Administration, the parties agree that Simbec's sole obligation to
Company is to promptly refund all payments Company made to Simbec for Simbec's
work on or services for the study, exclusive of reasonable costs that may have
been paid to Simbec for travel expenses, copying, study supplies and other
similar variable costs not related to the conduct of the study. If FDA rejects
the study for any reason other than the negligence or intentional misconduct of
Simbec or the violation of any law, rule or regulation of applicable
governmental authority, the parties agree that Simbec has no obligation to
Company to refund any payments. The parties also agree that Simbec is not
liable or responsible for consequential, indirect, or economic damages, however
caused, including but not limited to lost profits. Company hereby acknowledges
that consequential, indirect and economic losses are contingent and hypothetical
and therefore the parties agree that as liquidated damages, Simbec shall be
liable only for an amount of money equal to the payments it has received for its
work on and services for the Study.
ARTICLE X - BINDING AND FINAL ARBITRATION
In consideration for each others `promises and obligations herein, the parties
agree that if at any time any question, dispute, or difference arises between
Company and Simbec or Company and Simbec regarding the study agreement, the
matter will be submitted to binding and final arbitration in North Carolina,
United States. Such Arbitration shall be held pursuant to the rules of the
American Arbitration Association.
ARTICLE XI - EFFECTIVE DATES
This agreement is effective the day it has become signed by each of the parties.
The agreement remains effective until the study is completed, terminated, or
after ninety (90) days from the submission of the final data for the study. The
proposed time schedule for the study is shown in Appendix 2.
ARTICLE XII - FORCE MAJEURE
No party shall be in breach of this agreement because of an act of God, fire,
storm, explosion, government legislation or regulation, war, civil commotion,
strike, insurrection, embargo, energy shortage or failure or any other reason
beyond the control of either party. The parties agree to notify each other
promptly of any force majeure that will effect the party's ability to perform as
required under this agreement.
ARTICLE XIII - WAIVER
No breach of any provision of this agreement by the parties can be waived unless
the waiver is in writing. Waiver of one breach shall not be deemed a waiver of
any other breach of the same or any other provision.
ARTICLE XIV - POSTPONEMENT, CUBTAILMENT/EARLY TERMINATION
In the event of postponement of the Project by the Company after scheduled dates
for commencement have been agreed by both parties, Simbec shall be reimbursed
for all reasonable additional costs incurred, including subject screening costs,
etc. Further, [CONFIDENTIAL TREATMENT REQUESTED].
The company shall have the privilege of curtailing or terminating the study
immediately upon written notice to Simbec. Simbec reserves the right to
terminate without notice or penalty the study where Simbec deems necessary:
a. in the interest of subject safety;
b. in order to comply with the requirements of any governmental agency, board or
department; and
c. in order to comply with the decision of any judicial authority.
In the event of termination, the Company shall pay Simbec for that proportion of
the price of the project represented by the work Simbec have completed or is
irrevocably obligated to complete. Further, additional costs associated with
loss of revenue are payable, [CONFIDENTIAL TREATMENT REQUESTED].
The termination or curtailment of this Agreement shall not relieve either party
of its obligation to the other in respect of (i.) maintaining confidentiality,
(ii) obtaining consent for advertising and publication. (iii) indemnification.
(iv.) compensation for services performed and, (v.) appropriate reporting of any
data obtained.
ARTICLE XV - ENTIRE AGREEMENT
The provisions of this agreement and the attachments hereto constitute the final
and entire agreement between the parties. All prior negotiations, statements,
agreements and understandings between the parties are hereby canceled and
superseded by this agreement.
ARTICLE XVI - ACKNOWLEDGEMENT OF REVIEW AND UNDERSTANDING
Each party acknowledges and represents that it has read and fully understands
and agrees to all provisions contained in this agreement and has had the
opportunity to review and revise this agreement and the exhibits attached
hereto.
ARTICLE XVII - EXECUTION
The parties agree that this agreement and its exhibits may be executed in two or
more counterparts, each of which is deemed to be one and the same instrument.
Signed: /s/ ▇▇▇▇ ▇▇▇▇▇▇ /s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇
--------------- ----------------------
Name: ▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇, PhD
Title: Research Manager President and CEO
Date: 26 Aug 99 8/30/99
------------------- ---------------------------
For: Simbec Research Ltd Inspire Pharmaceuticals Ltd
APPENDIX 1
Exhibit 1: Cost Quotation
QUOTATION
▇▇ ▇▇▇ ▇▇▇▇▇ SIMBEC LOGO
To: Inspire Pharmaceuticals Inc
▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇ ▇▇▇
▇▇▇▇▇▇
▇▇ ▇▇▇▇▇
▇▇▇
DATE: 09 JULY 1999
QUOTATION NO: RD580/22385 (Issue 2)
COSTS OF A DOUBLE-MASKED, RANDOMISED, PLACEBO-CONTROLLED, RISING DOSE
STUDY OF MULTIPLE OCULAR INSTILLATIONS OF INS 365 OPTHALMIC SOLUTION IN
PATIENTS WITH MILD TO MODERATE DRY EYE DISEASE
Item Hours Events Unit Per Number Total
Price/ ((Pounds)
Hr Rate Sterling)
-----------------------------------------------------------------------------------------------------------
1 Protocol Design * Study
Protocol Review 1 *
sub-Total *
-----------------------------------------------------------------------------------------------------------
2 Case Record Forms
CRF Design * Page 24 *
CRF Review * CRF 62 *
CRF Binding & Printing - Triplicate * Page 1488 *
sub-Total *
-----------------------------------------------------------------------------------------------------------
3 Ethics/Regulatory
Presentation to LRECs * Per LREC 2 *
Presentation to Simbec Ethics * Study 1 *
Committee sub-Total *
-----------------------------------------------------------------------------------------------------------
4 Patients
Patient Recruitment * Subject 62 *
Patient Screening: pre Study * Subject 62 *
Opthalmic/Slit Lamp/IO Pressure * Subject 62 *
Examinations * Subject 62 *
Patient Screening: post Study * Subject 62 *
Patient Payments sub-Total *
-----------------------------------------------------------------------------------------------------------
5 Pharmacy
Trial Supplies Administration * Study 1 *
Dosing * Study Phase 4 *
sub-Total *
-----------------------------------------------------------------------------------------------------------
Carried forward *
-------------------------------------
* [CONFIDENTIAL TREATMENT REQUESTED]
SIMBEC RESEARCH LIMITED
Merthyr ▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇
Tel: ▇(▇) ▇▇▇▇ ▇▇▇▇▇▇ Fax ▇(▇) ▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇ ▇▇. ▇▇-▇▇▇ ▇▇/▇▇
▇▇▇▇▇▇ [Logo]
SIMBEC
Page 2
RD580/22385 (Issue 2)
COSTS OF A DOUBLE-MASKED, RANDOMISED, PLACEBO-CONTROLLED, RISING DOSE
STUDY OF MULTIPLE OCULAR INSTILLATIONS OF INS 365 OPTHALMIC SOLUTION IN
PATIENTS WITH MILD TO MODERATE DRY EYE DISEASE
Item Hours Events Unit Price/ Per Number Total
Hr Rate ((Pounds)
Sterling)
-----------------------------------------------------------------------------------------------------------------------
-----------------------------------------------------------------------------------------------------------------------
Brought forward *
-----------------------------------------------------------------------------------------------------------------------
6 Study Conduct, Supervision, etc
(1) Per Group of 8 Subjects (Cohorts 1-4)
In-House Overnight Pre Dosing 4 * Days 1 *
Main Study Days 48 * Days 1 *
Minor Study Days 8 * Days 1 *
Medical Supervision 8 * Days 1 *
Opthalmic/Slit Lamp/IO Pressure Examinations * Patient/Event 40 *
Bed occupancy 8 * Patient/Day 2 *
Catering 8 * Patient/Day 2 *
sub-Total *
-----------------------------------------------------------------------------------------------------------------------
Per Cohorts 1-4 sub-Total *
-----------------------------------------------------------------------------------------------------------------------
Study Conduct, Supervision, etc
(II) Per Group of 6 Subjects (Cohort 5)
In-House Overnight Pre Dosing 4 * Days 1 *
Main Study Days 40 * Days 1 *
Minor Study Days 8 * Days 1 *
Medical Supervision 8 * Days 1 *
Ophthalmic/Slit Lamp/IO Pressure Examinations * Patient/Event 30 *
Schirmar test * Patient/Event 120 *
Bed occupancy 6 * Patient/Day 2 *
Catering 6 * Patient/Day 2 *
sub-Total *
-----------------------------------------------------------------------------------------------------------------------
Per Cohort 5 sub-Total *
-----------------------------------------------------------------------------------------------------------------------
Principal Investigator fees * Study 1 *
-----------------------------------------------------------------------------------------------------------------------
Per Study sub-Total *
-----------------------------------------------------------------------------------------------------------------------
7 Pre-Study Laboratory Testing
Biochemistry/Haematology/Urinalysis/DoA * Specimen 45.00 *
Virology * Specimen 22.00 *
sub-Total *
-----------------------------------------------------------------------------------------------------------------------
sub-Total *
-----------------------------------------------------------------------------------------------------------------------
8 Post Study Laboratory Testing
Biochemistry/Haematology/Urinalysis * Samples @ 30.00 *
sub-Total *
-----------------------------------------------------------------------------------------------------------------------
9 Meetings with Sponsor
Meetings/Monitoring attendance * Meeting 4 *
sub-Total *
-----------------------------------------------------------------------------------------------------------------------
Carried forward *
------------------------------------------
* [CONFIDENTIAL TREATMENT REQUESTED]
SIMBEC RESEARCH LIMITED
Merthyr ▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇
Tel: ▇(▇) ▇▇▇▇ ▇▇▇▇▇▇ Fax ▇(▇) ▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇ ▇▇. ▇▇-▇▇▇ ▇▇/▇▇
▇▇▇▇▇▇ [Logo]
SIMBEC
Page 3
RD580/22385 (Issue 1)
COSTS OF A DOUBLE-MASKED, RANDOMISED, PLACEBO-CONTROLLED, RISING DOSE
STUDY OF MULTIPLE OCULAR INSTILLATIONS OF INS 365 OPTHALMIC SOLUTION IN
PATIENTS WITH MILD TO MODERATE DRY EYE DISEASE
Item Hours Events Unit Price/ Per Number Total
Hr Rate ((Pounds)
Sterling)
-------------------------------------------------------------------------------------------------------------------
-------------------------------------------------------------------------------------------------------------------
Brought forward *
-------------------------------------------------------------------------------------------------------------------
10 Data Management
Database and Data Entry Screen design 16 * Study 1 *
CRF Page Double Data Entry * CRF Page 1488 *
Data Validation, queries & resolution * CRF 62 *
Study Close out * Subject 62 *
Database lock * Study 1 *
Statistical Analysis 30 * Study 1 *
sub-Total *
-------------------------------------------------------------------------------------------------------------------
11 Quality Assurance
Protocol, CRF and Reports 12 * Study 1 *
Study Monitoring 16 * Study 1 *
sub-Total *
-------------------------------------------------------------------------------------------------------------------
12 Reports
Final Study Report Writing 35 * Study 1 *
Final Study Report production 20 * Study 1 *
sub-Total *
-------------------------------------------------------------------------------------------------------------------
13 Project Management
80 * Study 1 *
sub-Total *
-------------------------------------------------------------------------------------------------------------------
TOTAL ((Pounds) Sterling) *
-------------------------------------------------------------------------------------------------------------------
* [CONFIDENTIAL TREATMENT REQUESTED]
Additional: 1. Patient referral Costs and Screening Payments @
(Pounds)250.00 per patient eligible for screening
2. Packaging and Shipment of Samples/Trial Supplies - at cost
plus * handling charge.
QUOTATION ACCEPTANCE
I/We accept this quotation and wish the study to proceed subject to contract
Signed: /S/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇ Position in Company: Pres & CEO
---------------------- -----------
Date: 8/30/99
----------
SIMBEC RESEARCH LIMITED
Merthyr ▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇
Tel: ▇(▇) ▇▇▇▇ ▇▇▇▇▇▇ Fax ▇(▇) ▇▇▇▇ ▇▇▇▇▇▇
VAT No.: GB 289 0833 21 Registered in England No. 1191772
Protocol ▇▇. ▇▇-▇▇▇ ▇▇/▇▇
▇▇▇▇▇▇▇▇ ▇
▇▇▇▇▇ ▇▇▇▇▇▇▇▇
Protocol No 03-102 RD580/22385
Study Schedule
Dose first subject: *
Complete dosing
of cohorts 1-4: *
Dispatch safety summary
for cohorts 1-4: *
First dose of cohort 5: *
Dose final subject: *
Lock database: *
Dispatch draft report: *
Dispatch final report: Two weeks after receipt of sponsor
comments on draft report.
*[CONFIDENTIAL TREATMENT REQUESTED]