Clinical Research Agreement B/w Inspire & Simbec

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 ...