Document:

<PAGE>

                                                                    Exhibit 10.5

[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.]

                          SPONSORED RESEARCH AGREEMENT

     RESEARCH AGREEMENT, effective March 10, 1995 (the "Effective Date"), by and
between The University of North Carolina at Chapel Hill, having an address at
300 Bynum Hall, Chapel Hill, North Carolina (the "University"), and Inspire
Pharmaceuticals, Inc., a corporation existing, under the laws of the State of
Delaware, and having its principal place

of business at c/o Burr, Egan, Deleage & Co., One Post Office Square, Boston,
Massachusetts (the "Sponsor").

                                  WITNESSETH:

     WHEREAS, in pursuit of its educational purposes, which include research and
training, the University undertakes scholarly research and experimental
activities in a variety of academic disciplines; and

     WHEREAS, the Sponsor wishes to fund, and desires that the University
undertake, a research program in accordance with said research and training
mission, which research program is described more fully in Exhibit A, attached
hereto and made a part hereof (hereinafter, the "Research"); and

     WHEREAS, in furtherance of its scholarly research and instructional
interests, the University is willing to undertake the Research upon the terms
and conditions set forth
below;

     NOW, THEREFORE, in consideration of the premises and mutual covenants
herein contained, the parties hereto agree as follows:

     1.  Scope of Research
         -----------------

     During the term of this Agreement, the University shall, use its best
efforts to perform

the Research, as described in Exhibit A, attached hereto and made a part hereof.
Notwithstanding the foregoing, the University makes no warranties or
representations regarding its ability to achieve any particular research
objective or results.

     2.  Personnel
         ---------

     The Research shall be performed by, and under the supervision and direction
of, Dr. Richard C. Boucher, who shall be designated the Principal Investigator,
together with Drs. Ken Harden and Jack Stutts and such additional personnel as
may be assigned by the
<PAGE>

University. If for any reason the Principal Investigator is unable to continue
to serve as Principal Investigator, and a successor acceptable to both the
University and the Sponsor is not available, this agreement may be terminated as
provided in Article 10 (b).

     3.    University Policies and Procedures
           ----------------------------------

     All Research conducted hereunder shall be performed in accordance with
established University policies and procedures, including, but not limited to,
policies and procedures applicable to research involving human subjects,
laboratory animals, and hazardous agents and materials.

     4.    Reimbursement of Costs
           ----------------------

     The Sponsor shall reimburse the University for all direct and indirect
costs incurred by the University in connection with the Research in accordance
with the budget set forth on Exhibit B. Provided, however, that the University
may submit to the Sponsor at any time, and the Sponsor may at its discretion
approve in writing, requests for additional funds. Any such written approval
shall constitute a modification of the Agreement. However, the Sponsor is not
liable for any cost in excess of the amount specified herein, unless this
Agreement is modified to indicate such in writing by both parties. All checks
shall be made payable to The University of North Carolina at Chapel Hill, shall
include reference to the University Principal Investigator and his department,
and shall be sent to:

     S. Kent Walker
     University of North Carolina at Chapel Hill
     Office of Contracts and Grants
     440 West Franklin Street
     Chapel Hill, NC 27599
     Tel: (919) 966-5625
     Fax: (919) 962-0646

Payments shall be made in accordance with the schedule set forth on Exhibit B.

     5.  Research Reports
         ----------------

     The University and its employees will prepare and maintain records,
including bound laboratory notebooks maintained in accordance with standard
scientific procedures, containing all appropriate data reflecting the results of
the Research.  The Principal Investigator shall furnish to the Sponsor during
the term of this Agreement periodic informal written reports regarding the
progress of the Research.  The Principal Investigator, or a mutually agreeable
substitute, shall meet with representatives of the Sponsor at the reasonable
request of the Sponsor to facilitate exchange of information regarding the
Research. Unless such meeting takes place at the University, the meeting shall
be at the expense of Sponsor, including travel. A final report setting forth the
significant research findings shall be prepared by the Principal Investigator
and submitted to the Sponsor within ninety (90) days following the expiration of
the term of this Agreement or the effective date of early termination, as set
forth in Article 10.

                                      -2-
<PAGE>

     6.   Publication
          -----------

     The University will be free to publicly disclose (through journals,
lectures, or otherwise) the results of the research, provided that the
University shall have provided a copy of the proposed publication to the Sponsor
at least sixty (60) days prior to the intended submission of any written
publication and at least thirty (30) days prior to any other public disclosure
to allow the Sponsor to determine whether any patentable invention or Sponsor's
Confidential Information (as defined below) would be disclosed.

     If the proposed disclosure contains Sponsor's Confidential Information, the
University shall remove or cause the author to remove such Sponsor Confidential
Information prior to its submission for publication or other public disclosure.
If the proposed disclosure would disclose a patentable invention, the University
shall, at the request of the Sponsor, delay or cause the author to delay
submission of the work for publication or other public disclosure for up to an
additional sixty (60) days to enable the University or the Sponsor to file a
patent application. If the Sponsor has obtained an extension for the thirty-day
evaluation period as set forth in this Section 6, the Sponsor shall use
reasonable efforts to reduce this sixty-day filing period by the amount of time
previously granted in the extension.

     As between the Sponsor and the University, the University shall have
ownership of any copyrights or copyrightable materials first produced or
composed by or on behalf of the University by its faculty, staff, employees and
agents.  The Sponsor shall have ownership of all copyrightable materials that
contain Confidential Information of the Sponsor; University shall either cause
such Confidential Information to be removed from such materials or assign
copyright to such materials to the Sponsor.  In addition, the University shall
grant to the Sponsor upon request an irrevocable, royalty-free, nonexclusive
right to reproduce, translate, and use, for the Sponsor's own purposes, which
purposes shall not conflict with any other provision of this Agreement, all of
the University's copyrighted material derived from the results of the Research.

     The Sponsor, at its election, shall be entitled to receive in any
publication describing the results of the Research an acknowledgment of its
sponsorship of the Research.

     It is specifically agreed that nothing contained in this agreement will
interfere with the oral defense of research theses and dissertations of graduate
students.

     7.   Proprietary Information
          -----------------------

     All confidential information of either party disclosed to the other party
in connection with the Research hereunder ("Confidential Information") will be
treated by the receiving party as confidential and restricted in its use to only
those uses contemplated by the terms of this Agreement. Any information which is
to be treated as confidential must be clearly marked as confidential prior to
transmittal to the other party. If such Confidential Information is disclosed
orally, it shall be identified as being confidential at the time of disclosure,
and shall thereafter be summarized in writing within 30 days, marked as
confidential, and transmitted to the receiving party. The Sponsor may submit
Confidential

                                      -3-
<PAGE>

Information only to the Principal Investigator, who shall be free to refuse to
accept such Confidential Information. The obligations of this paragraph shall
survive and continue for five (5) years after termination of this Agreement.
Specifically excluded from such confidential treatment shall be information
which: (a) as of the date of disclosure and/or delivery, is already known to the
party receiving such information; (b) is or becomes part of the public domain,
through no fault of the receiving party; (c) is lawfully disclosed to the
receiving party by a third party who is not obligated to retain such information
in confidence; (d) is independently developed at the receiving party, as
demonstrated by its written records, by someone not privy to the Confidential
Information; or (e) is required to be disclosed to comply with applicable laws
or governmental regulations, provided that the disclosing party receives prior
written notice of such disclosure and that the receiving party takes all
reasonable and lawful actions to minimize the extent of such disclosure and, if
possible, to avoid such disclosure.

     From time to time, the Sponsor may also provide the University with
biological, chemical, or physical materials ("Materials") for use in the
Research; Materials shall be proprietary to the Sponsor if they were developed
prior to or outside the performance of this Agreement ("Proprietary Materials").
University shall not, and shall take reasonable steps to assure that its
faculty, staff, employees, and agents will not, either: (1) use the Proprietary
Materials for any purpose other than the conduct of the Research, or (2) make
the Proprietary Materials available to third party without the prior written
consent of the Sponsor. Materials developed in the performance of this Agreement
shall be treated as described in Section 8.

     Each party shall retain full ownership of any Confidential Information or
Proprietary Materials in the possession of the other party. At the termination
of this Agreement, each party shall use its best efforts to secure the return
of, or destroy, any Confidential

Information or Proprietary Materials that are in its possession and are owned by
the other party, unless such party grants specific written permission to retain
possession of such Confidential Information or Proprietary Materials.

     8.   Inventions
          ----------

     a.   All rights in any inventions or discoveries (including all Materials),
whether or not patentable, that are developed, conceived, or reduced to practice
in the course of the Research solely by University employees shall be property
of the University ("University Inventions"). All rights in any inventions or
discoveries (including Materials) whether or not patentable, that are developed,
conceived, or reduced to practice jointly by University employees and Sponsor
employees in the course of the Research shall be jointly owned by the University
and the Sponsor ("Joint Inventions"). All rights in any inventions or
discoveries (including Materials) whether or not patentable, that are developed,
conceived, or reduced to practice in the course of the Research solely by
Sponsor employees shall be property of the Sponsor. The University shall
promptly report to the Sponsor any University Inventions or Joint Inventions by
University employees.

                                      -4-
<PAGE>

     b.   The University hereby grants the Sponsor a first option to obtain an
exclusive license under any University Inventions or Joint Inventions that are
conceived and reduced to practice during the term of this Agreement. The
University agrees to notify the Sponsor of any such Inventions promptly and in
writing. This option for Inventions shall become effective when the Sponsor
receives notice from the University and shall remain open for ninety (90) days.
During, this ninety (90) day period, the University shall make available to the
Sponsor information that the Sponsor reasonably requests which would be useful
and necessary in evaluating such Invention, subject to reasonable
confidentiality requirements that may be imposed by the University. The Sponsor
shall indicate the exercise of its option by written notification to the
University. Upon receipt of such notice, the University shall automatically
grant the Sponsor an exclusive license under such Invention under the terms of
the License Agreement attached hereto as Exhibit C (the "License Agreement"),
                                         ---------
whereupon such Invention shall become a "Licensed Improvement" under the terms
of such License Agreement.

     c.  The University also grants the Sponsor a right of first negotiation,
during the sixty-day period immediately following the termination of this
Agreement, to obtain an exclusive license under any University Inventions and
Joint Inventions that arise as a direct result of the sponsored research
("Developments"). The University agrees to notify the Sponsor of any
Developments promptly and in writing. The Sponsor shall have the right of first
negotiation with respect to a given Development for a period of sixty (60) days
after the Sponsor receives notice of that Development.  The University shall
promptly make available to the Sponsor any information that the Sponsor
reasonably requests which would be useful and necessary in evaluating a
Development, subject to reasonable confidentiality requirements that may be
imposed by the University.  In the event that the Sponsor desires to obtain an
exclusive license to any Development, the University agrees to negotiate in good
faith the terms and conditions of such license. If the parties cannot reach
agreement on the terms of an exclusive license to a Development within the
sixty-day negotiation period, the University shall be free to offer that
Development to third parties; provided, however, that for a period of eighteen
(18) months if the University offers to a third party the opportunity to license
such Development on financial terms that are more favorable than the financial
terms last offered to the Sponsor, then the University shall offer the Sponsor
an opportunity to license such Development on the same terms as those offered by
the University to such third party.

     d.  If the Sponsor fails to exercise its exclusive license option to any
Invention within the applicable option period, or if the Sponsor notifies the
University in writing that it will not exercise such option, then the University
shall be free to offer its rights in such Invention to any third parties. The
foregoing notwithstanding, the Sponsor retains its rights in any Joint
Invention.

     e.  During any option period applicable to a University Invention, the
University agrees, if requested by the Sponsor, to cause U.S. or foreign patent
applications to be filed and prosecuted in its name at the Sponsor's expense,
using patent counsel reasonably acceptable to the Sponsor. The University shall
consult with the Sponsor regarding the preparation, filing, prosecution, and
maintenance of such patent applications and shall furnish to the Sponsor copies
of documents relating thereto in sufficient time to enable the Sponsor to
comment on them prior to filing. If the Sponsor declines to license such
University Invention,

                                      -5-
<PAGE>

then the University shall have no further obligation to obtain patent protection
for such Invention and the Sponsor shall have no further obligation to reimburse
the University for its expenses. If the Sponsor elects to license such
University Invention, then the responsibility for patenting such Inventions and
any associated expenses shall be governed by the terms of the resulting license
agreement. In the event that the University desires to file a patent application
with respect to a University Invention, and the Sponsor does not agree within
sixty (60) days after receipt of written notification from the University of its
intent to file such patent application, the University may file and prosecute
such patent at its own expense and the Sponsor shall have no farther rights
under this Agreement with respect to such University Invention.

     f.  During any option period applicable to a Joint Invention, the Sponsor
shall have the first right to cause patent applications to be filed and
prosecuted in the names of both parties at the Sponsor's expense using patent
counsel reasonably acceptable to the University. The Sponsor shall consult with
the University regarding the preparation, filing, prosecution, and maintenance
of such patent applications and shall furnish to the University copies of
documents relating thereto in sufficient time to enable the University to
comment on them prior to filing. If the Sponsor elects to license such Joint
Invention, then the responsibility for patenting such Inventions and any
associated expenses shall be governed by the terms of the resulting license
agreement. If the Sponsor elects not to license such Joint Invention or not to
seek patent protection for such Invention, then the University shall be free to
cause patent applications to be filed and prosecuted in the names of both
parties at the University's expense using patent counsel reasonably acceptable
to the Sponsor. The University shall consult with the Sponsor regarding the
preparation, filing, prosecution, and maintenance of such patent applications
and shall furnish to the Sponsor copies of documents relating thereto in
sufficient time to enable the Sponsor to comment on them prior to filing.

     9.  Ownership of Property
         ---------------------

     Title to any equipment purchased or manufactured in the performance of the
work funded under this agreement shall vest in the University.

     10.  Term and Termination
          --------------------

     a.   This Agreement shall commence on the Effective Date and remain in
effect for a period of two (2) years and may be extended thereafter by mutual
agreement of the parties in writing.

     b.   Notwithstanding the foregoing, this Agreement may be terminated by
either party at any time upon sixty (60) days advance written notice to the
other party. Upon receipt of notice of early termination, the University shall
use its best efforts promptly to limit or terminate any outstanding commitments
and to conclude the work. All costs associated with such termination shall be
reimbursable, including, without limitation, all non- reimbursed costs and non-
cancelable commitments incurred prior to the receipt of the notice of
termination, such reimbursement together with other payments not to exceed the
total estimated project cost specified in Article 4.

                                      -6-
<PAGE>

     c.   The provisions of paragraphs 5, 6, 7, 8, 9, 12, 14, 15, and 20 shall
survive such termination of this Agreement.

     11.  Notices
          -------

     Any notices given under this Agreement shall be in writing and shall be
deemed delivered when received by means of confirmed facsimile transmission or
recognized national overnight courier or when sent by first-class mail, postage
paid, addressed or transmitted to the parties as follows (or at such other
addresses or facsimile numbers as the parties may notify each other of in
writing):

                The University of North Carolina At Chapel Hill:
                ------------------------------------------------

Dr. Robert P. Lowman
Director
Office of Research Services
The University of North Carolina at Chapel Hill
CB #4100, 300 Bynum Hall
Chapel Hill, NC 27599-4100
Ph:   (919) 966-5625
Fax:   (919) 962-0646

                                    Sponsor:
                                    --------

H. Jeff Leighton
President and Chief Executive Officer
Inspire Pharmaceuticals, Inc.
c/o Burr, Egan, Deleage & Co.
One Post Office Square
Boston, MA 02110
Ph: (617) 482-8020
Fax: (617) 566-0848

With a copy to:

Michael Lytton, Esq.
Palmer & Dodge
One Beacon Street
Boston, MA 02108
Fax: (617) 227-4420

     12.  Use of University Name
          ----------------------

     Sponsor shall not employ or use the name of the University in any
promotional materials, advertising, or in any other manner without the prior
express written permission of the University, except that Sponsor may, during
the term of this Agreement, state that it is sponsoring the Research by the
Principal Investigator at the University.  The foregoing

                                      -7-
<PAGE>

notwithstanding, Sponsor shall have the right to identify the University and to
disclose the terms of this Agreement in any prospectus, offering memorandum, or
other document or filing required by applicable securities laws or other
applicable law or regulation, provided that Sponsor shall have given University
at least five (5) days prior written notice of the proposed text of any such
identification or disclosure for the purpose of giving University the
opportunity to comment on such proposed text. In no event shall the sponsoring
of the Research be considered to be an endorsement of the Sponsor by the
University of any commercial product which may result, indirectly or directly,
from the Research.

     13.  Relationship of the Parties
          ---------------------------

     The University, for all purposes related to this Agreement, shall be deemed
an independent contractor of the Sponsor, and nothing in this Agreement shall be
deemed to create a relationship of employment or agency or to constitute the
parties as partners or joint venturers.

     14.  Indemnification
          ---------------

     The Sponsor hereby agrees to indemnify, defend and hold harmless the
University, its employees, students and agents from and against any loss, claim,
damage or liability of any kind arising out of or in connection with the act(s)
or failure(s) to act of Sponsor's employees or agents in connection with the
performance of this Agreement, and/or involving Sponsor's use and/or possession
of the results of the Research and/or biological samples or other Materials
provided by the University to the Sponsor pursuant to the Research.

     15.  No Warranties
          -------------

     The University makes no warranties, either express or implied, as to any
matter, including, without limitation, the results of the research or any
inventions or product, tangible or intangible, conceived, discovered or
developed under this Agreement; or the merchantability or fitness for a
particular purpose of the research results of any such invention or product. The
University shall not be liable for any direct, consequential or other damages
suffered by the Sponsor or by any Licensee or any others resulting from the use
of the research results or any such invention or product.

     16.  Force Majeure
          -------------

     The University shall not be liable for any failure to perform as required
by this Agreement, to the extent such failure to perform is caused by any reason
beyond the University's control, or by reason of any of the following: labor
disturbances or disputes of

                                      -8-
<PAGE>

any kind, accidents, failure of any required governmental approval, civil
disorders, acts of aggressions, acts of God, energy or other conversation
measures, failure of utilities, mechanical breakdowns, material shortage,
disease, or similar occurrences.

     17.  Severability
          ------------

     In the event that a court of competent jurisdiction holds any provision of
this Agreement to be invalid, such holding shall have no effect on the remaining
provisions of this Agreement, and they shall continue in full force and effect.

     18.  Entire Agreement; Amendments
          ----------------------------

     This Agreement and the Exhibits hereto contain the entire agreement between
the parties. No amendments or modifications to this Agreement shall be effective
unless made in writing and signed by authorized representatives of both parties.

     19.  Similar Research
          ----------------

     Nothing in this Agreement shall be construed to limit the freedom of the
University or of its researchers who are participants under this Agreement, from
engaging in similar research made under other grants, contracts or agreements
with parties other than the Sponsor, provided that the Sponsor receives advance
written notice describing any research not funded by the Federal Government.
The Sponsor agrees to maintain all such disclosures in strict confidence.

     20.  Governing Law
          -------------

     This Agreement shall be governed by and construed in accordance with the
law of North Carolina.

                                      -9-
<PAGE>

     IN WITNESS HEREOF, the parties hereto have executed this Agreement by their
duly authorized officers or representatives.

THE UNIVERSITY OF NORTH CAROLINA       INSPIRE PHARMACEUTICALS,
CHAPEL HILL                            INC.

By:    /s/ Wayne R. Jones                By:      /s/ H. Jeff Leighton
    --------------------------               -------------------------------
       Wayne R. Jones                           H. Jeff Leighton, Ph.D
       Vice Chancellor,                         President & Chief Executive
       Business and Finance                     Officer

Consented to by Principal Investigator:

By:    /s/ Richard C. Boucher
    ------------------------------
       Richard C. Boucher

                                      -10-
<PAGE>

                                   Exhibit A
                                   ---------

                            Description of Research

Exhibit A-1:   Research Plan for Dr. T. Kendall Harden.
-----------
               [CONFIDENTIAL TREATMENT REQUESTED]

Exhibit A-2:   Research Plan for Dr. M. Jackson Stutts.
-----------
               [CONFIDENTIAL TREATMENT REQUESTED]

Exhibit A-3:   Research Plan for Dr. Richard C. Boucher.
-----------
               [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                                   Exhibit B
                                   ---------

                              Budget for Research

                      [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                                   Exhibit C
                                   ---------

                               License Agreement
<PAGE>

                   Extension of Sponsored Research Agreement

This Extension of Sponsored Research Agreement is dated as of March 7, 1997 by
and between the University of North Carolina at Chapel Hill (the "University")
and Inspire Pharmaceuticals, Inc. (the "Company").  The University and the
Company agree to extend the Sponsored Research Agreement, effective March 10,
1995, as previously amended (the Agreement"), as follows:

     1.  The term of the Agreement shall be extended until the date on which the
University and the Company execute an Amendment to the Agreement, but no later
than September 30, 1997.

     2.  All other terms and conditions of the Agreement shall remain in full
force and effect.

The University of North Carolina                Inspire Pharmaceuticals, Inc.
At Chapel Hill

By:     /s/ Robert P Lowman                          /s/ David J. Drutz
    -----------------------------------------        --------------------------
                                                         David J. Drutz, M. D.
Title:  Director, Office of Research Services               President and CEO
       --------------------------------------
<PAGE>

Extension of Sponsored Research Agreement

This Extension of Sponsored Research Agreement is dated as of October 1, 1997 by
and between the University of North Carolina at Chapel Hill (the "University")
and Inspire Pharmaceuticals, Inc. (the "Company").  The University and the
Company agree to extend the Sponsored Research Agreement, effective March 10,
1995, as previously amended (the "Agreement"), as follows:

        1.   The term of the Agreement shall be extended until the date on which
the University and the Company execute an Amendment to the Agreement, but no
later than September 30, 1998.

        2.   All other terms and conditions of the Agreement shall remain in
full force and effect.

The University of North Carolina                Inspire Pharmaceuticals, Inc.
At Chapel Hill

By:      /s/ Robert P. Lowman                      By:   /s/ David J. Drutz
    ------------------------------------------        -------------------------
                                                        David J. Drutz, M.D.
                                                          President and CEO
Title:  Director, Office of  Research Services
       ---------------------------------------
<PAGE>

                                   AMENDMENT

This Amendment, made and entered into this 30th day of September, 1998, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered into a Sponsored Research Agreement
dated March 10, 1995, and have mutually agreed to amend said Sponsored Research
Agreement on December 4, 1995, June 6, 1996, March 7, 1997, and October 1, 1997,
hereinafter referred to as the "Agreement"; and

WHEREAS, the parties desire to continue the research activities being conducted
under the Agreement as well as to conduct additional research initiatives under
the same terms and conditions of the Agreement; and

WHEREAS, this amendment is in accordance with the amendment provision
authorizing amendments in writing executed by the duly authorized officials of
both parties.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1.  Paragraph 10, Term and Termination shall be amended as follows:
                  --------------------

"This Agreement shall commence on the Effective Date and shall continue through
September 30, 2000 and may be extended thereafter by mutual agreement of the
parties in writing."

2. All terms of the Agreement not altered by this Amendment shall remain in full
force and effect throughout the term of said Agreement.

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

FOR AND ON BEHALF OF                   FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.          UNIVERSITY OF NORTH
                                       CAROLINA AT CHAPEL HILL
   /s/ Janet L. Rideout
-----------------------------
Signature                                  /s/ Robert P. Lowman
                                       --------------------------
                                       Signature
       Janet L. Rideout
-----------------------------
Name                                       Robert P. Lowman, Ph.D.
                                       --------------------------
                                       Name
   V.P. Discovery
-----------------------------
Title                                     Director, Office of Research Services
                                       ----------------------------------------
                                       Title

Date:     OCT 2, 1998                  Date:    OCT 13 1998
-----------------------------                ----------------------
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                   AMENDMENT

This Amendment, made and entered into this 9th day of December, 1998 by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Sponsored Research Agreement dated
March 10, 1995, hereinafter referred to as the "Agreement"; and

WHEREAS, this amendment is in accordance with the amendment provision
authorizing amendments in writing executed by the duly authorized officials of
both parties.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follow:

1.  Article 1, Scope of Research, is amended by adding the following:
               -----------------

"University shall use its best efforts to perform the research as described in
Exhibit A-6."

2.  Article 2, Personnel, is amended by adding the following:
               ---------

"The Research described in Exhbit A-6 shall be performed under the supervision
and direction of Dr. Richard Boucher, together with additional personnel as may
be assigned by the University."

3.  Article 4, Reimbursement of Cost, shall be amended by adding the following:
               ---------------------

"The Sponsor shall agrees to pay the University for all direct and indirect
costs incurred by the University in connection with the Research described in
Exhibit A-6 in the amount not to exceed [CONFIDENTIAL TREATMENT REQUESTED].
Payment shall be made in accordance with the following schedule: one-quarter
(1/4) of the budget upon execution of this Amendment and equal quarterly
payments for the duration of the Research."
<PAGE>

4. Article 10, Term and Termination, shall be amended as follows:
               ---------------------

"The term for the Research to be performed under Exhibit A-6 shall be from
October 1, 1998 through September 30, 1999 and may be extended thereafter by
mutual agreement of the parties in writing.

5. All terms of the Agreement not altered by this Amendment shall remain in full
force and effect throughout the term of said agreement.

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

FOR AND ON BEHALF OF                FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.       UNIVERSITY OF NORTH
                                    CAROLINA AT CHAPEL HILL

     /s/ Janet L. Rideout
------------------------------
Signature                               /s/ Robert P. Lowman
                                    -------------------------------------------
                                    Signature

 Janet L. Rideout
------------------------------
Name                                   Robert P. Lowman, Ph.D.
                                    -------------------------------------------
                                    Name

    V.P. Discovery
------------------------------
Title                                   Director, Office of Research Services
                                    -------------------------------------------
                                    Title

Date:     DEC 9, 1998               Date:   JAN 14 1999
------------------------------            -------------------------------------

Agreed and Accepted:      /s/ Richard Boucher
                       ---------------------------
                       Dr. Richard Boucher
<PAGE>

                                                                     EXHIBIT A-6

                      [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                   AMENDMENT

This Amendment, made and entered into this 7th day of  April, 1999, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Sponsored Research Agreement dated
March 10, 1995, hereinafter referred to as the "Agreement"; and

WHEREAS, this amendment is in accordance with the amendment provision
authorizing amendments in writing executed by the duly authorized officials of
both parties.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1.  Article 1, Scope of Research, is amended by adding the following:
               -----------------

"University shall use its best efforts to perform the research as described in
Exhibit A-7 for the period of January 1, 1999 through December 31, 1999."

2.  Article, 2, Personnel, is amended by adding the following:
                ---------

"The Research described in Exhibit A-7 shall be performed under the supervision
and direction of Dr. M. Jackson Stutts and such additional personnel as may be
assigned by the University."

3.  Article 4, Reimbursement of Cost, shall be amended by adding the following:
               ---------------------

"The Sponsor shall agrees to pay the University for all direct and indirect
costs incurred by the University in connection with the Research described in
Exhibit A-7 in the amount not to exceed [CONFIDENTIAL TREATMENT REQUESTED],
bringing the total funding under the Master Research Agreement to [CONFIDENTIAL
TREATMENT REQUESTED]. Payment for one-half of the [CONFIDENTIAL TREATMENT
REQUESTED] supplement shall be made upon execution of this Amendment, with the
balance to be paid upon submission of the final report."
<PAGE>

4.  All terms of the Agreement not altered by this Amendment shall remain in
full force and effect throughout the term of said agreement.

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

FOR AND ON BEHALF OF                FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.       UNIVERSITY OF NORTH
                                    CAROLINA AT CHAPEL HILL

    /s/ Janet L. Rideout
-----------------------------
Signature                              /s/ Robert P. Lowman
                                    -------------------------------------
                                    Signature

         Janet L. Rieout
-----------------------------
Name                                    Robert P. Lowman, Ph.D.
                                    -------------------------------------
                                    Name

    V.P., Discovery
-----------------------------
Title                                Director, Office of Research Services
                                     -------------------------------------
                                     Title

Date:   April 7, 1999                Date:    APR 23 1999
-----------------------------              -------------------------------

Agreed and Accepted:      /s/ M. Jackson Stutts
                       --------------------------------
                       Dr. M. Jackson Stutts
<PAGE>

                                                                     Exhibit A-7

                      [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                   AMENDMENT

This Amendment, made and entered into this 2nd day of July, 1999, by and between
The University of North Carolina at Chapel Hill, hereinafter referred to as the
"University" and Inspire Pharmaceuticals, Inc., hereinafter referred to as the
"Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Sponsored Research Agreement dated
March 10, 1995, hereinafter referred to as the "Agreement"; and

WHEREAS, this amendment is in accordance with the amendment provision
authorizing amendments in writing executed by the duly authorized officials of
both parties.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1.  Article 1, Scope of Research, is amended by adding the following:
               -----------------

"University shall use its best efforts to perform the research as described in
Exhibit A-8 for the period of April 1, 1999 through December 31, 1999."

2.  Article, 2, Personnel, is amended by adding the following:
                ---------

"The Research described in Exhibit A-8 shall be performed under the supervision
and direction of Dr. C. William Davis and such additional personnel as may be
assigned by the University."

3.  Article 4, Reimbursement of Cost, shall be amended by adding the following:
               ---------------------

"The Sponsor shall agrees to pay the University for all direct and indirect
costs incurred by the University in connection with the Research described in
Exhibit A-8 in the amount not to exceed

[CONFIDENTIAL TREATMENT REQUESTED], bringing the total funding under the Master
Research Agreement to [CONFIDENTIAL TREATMENT REQUESTED].  Payment for one-half
of the [CONFIDENTIAL TREATMENT REQUESTED] supplement shall be made upon
execution of this Amendment, with the balance to be paid upon submission of the
final report."
<PAGE>

4.  All terms of the Agreement not altered by this Amendment shall remain in
full force and effect throughout the term of said agreement.

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

FOR AND ON BEHALF OF                    FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.           UNIVERSITY OF NORTH
                                        CAROLINA AT CHAPEL HILL
/s/ Janet L. Rideout
------------------------------------
Signature                                   /s/ Robert P. Lowman
                                        ---------------------------------------
Janet L. Rideout                         Signature
------------------------------------
Name                                     Robert P. Lowman, Ph.D
                                        ---------------------------------------
V.P., Development                        Name
------------------------------------
Title                                    Director, Office of Research Services
                                        ---------------------------------------
                                         Title

Date:   July 2, 1999                     Date:  OCT 26 1999
      ------------------------------            -------------------------------

Agreed and Accepted:     /s/ C. William Davis
                        ---------------------------------
                         Dr. C. William Davis
<PAGE>

                                                                     Exhibit A-8

                      [CONFIDENTIAL TREATMENT REQUESTED].
<PAGE>

                                 INSPIRE

                                 PHARMACEUTICALS, INC.

-------------------------------------------------------------------------------

December 15, 1999

C. William Davis, Ph.D.
CB#7248, 6009 Thurston-Bowles Building
Chapel Hill, NC 27599-7248

Dear Dr. Davis:

This is to confirm our previous conversation and our agreement that the
Sponsored Research Agreement , "Purinergic Regulation of Ciliary Activity in the
Airways" for which you are the PI can be extended from Dec. 31 1999 to end March
31, 2000. Both Dr. Christy Shaffer and myself have approved this amendment to
the above Agreement to enable you to conduct some instrumental development work.

Payment of [CONFIDENTIAL TREATMENT REQUESTED] will be made to Account #5-58336.

Sincerely yours,

/s/ Janet L. Rideout

Janet L. Rideout, Ph.D.
VP, Discovery

CC:  Rebecca Owen

-------------------------------------------------------------------------------

4222 Emperor Boulevard, Suite 470 o Durham, North Carolina 27703
Telephone 919.941.9777 o Fax 919.941.9797
<PAGE>

                       THE UNIVERSITY OF NORTH CAROLINA
                                      AT
                                  CHAPEL HILL
<TABLE>
<S>                                                       <C>
Office of Contracts & Grants                              The University of North Carolina at Chapel Hill
Area Code 919-966-3411                                    Campus Box #135, 440 W. Franklin St.
FAX 919-962-5011                                          Chapel Hill, NC 27599-1350
</TABLE>

February 10, 2000

Ms. Janet Rideout, Ph.D.
Vice President, Discovery
Inspire Pharmaceuticals, Inc.
4222 Emperor Boulevard, Suite 470
Durham, NC 27703
919/941.9777

Dear Dr. Rideout:

Re:  Amendment to Sponsored Research Agreement between Inspire Pharmaceuticals,
Inc. and the University of North Carolina at Chapel Hill/UNC Account #5-58026,
UNCPI: M. Jackson Stutts

This Amendment made and entered into this 10th day of February 2000 by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Sponsor".

WHEREAS, the parties previously entered in a Sponsored Research Agreement dated
March 10, 1995, hereinafter referred to as the "Agreement".

WHEREAS, this Amendment is in accordance with the amendment provision
authorizing amendments in writing executed by duly authorized officials of both
parties:

NOW, THEREFORE, in consideration of the mutual promises contained herein and
other good and valuable consideration, the receipt and adequacy of which is
hereby acknowledged, the parties  hereto promise and agree as follows:

1.  The University will use its best efforts to perform the research as
described in Exhibit A for the period of January 1, 2000 through December 31,
2000.
<PAGE>

Janet Rideout, PH.D.                2                          February 10, 2000

2.   Sponsor shall pay the University during the term of the Amendment for all
     direct and indirect costs incurred by the University in connection with the
     Research, described in Exhibit A, in the amount not to exceed [CONFIDENTIAL
     TREATMENT REQUESTED]. Payment shall be made in accordance with the
     following schedule: one half (1/2) of the [CONFIDENTIAL TREATMENT
     REQUESTED] supplement shall be made upon the execution of this Amendment,
     with the balance to be paid upon submission of the Final Report. Budget
     attached as Exhibit B.

3.   Any and all provisions of the Agreement not expressly modified hereby will
     remain in full force and effect.

IN WITNESS THEREOF, the undersigned duly authorized representatives of the
parties have executed this first amendment.

Inspire Pharmaceuticals, Inc.

By:   /s/ Janet L. Rideout          By:    /s/ Robert P. Lowman
    ---------------------------         ----------------------------------------

Name:   Janet L. Rideout            Name:  Robert P. Lowman, Ph.D.
      -------------------------           --------------------------------------

Title:     V.P., Development        Title: Director, Office of Research Services
       ------------------------            -------------------------------------

Date:     2/15/00                   Date:    FEB 17 2000
       ------------------------            -------------------------------------

                                    Principal Investigator
                                    ----------------------

                                       /s/ Richard Boucher
                                    ----------------------

                                    Date:   2-17-00
                                          ----------------

<PAGE>

<TABLE>
<CAPTION>
                                               THE UNIVERSITY OF NORTH CAROLINA
                                                              AT
                                                          CHAPEL HILL
<S>                                                                                <C>
Office of Contracts & Grants                                                       The University of North Carolina at Chapel Hill
Area Code 919-966-3411                                                             Campus Box #135, 440 W. Franklin St.
FAX 919-962-5011                                                                   Chapel Hill, NC 27599-1350
</TABLE>

February 10, 2000

Ms. Janet Rideout, Ph.D.
Vice President, Discovery
Inspire Pharmaceuticals, Inc.
4222 Emperor Boulevard, Suite 470
Durham, NC 27703
919/941.9777

Dear Dr. Rideout:

Re:  Amendment to Sponsored Research Agreement between Inspire Pharmaceuticals,
Inc. and the University of North Carolina at Chapel Hill/UNC Account #5-58026,
UNCPI: Richard Boucher

This Amendment made and entered into this 10th day of February 2000 by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Sponsor".

WHEREAS, the parties previously entered in a Sponsored Research Agreement dated
March 10, 1995, hereinafter referred to as the "Agreement".

WHEREAS, this Amendment is in accordance with the amendment provision
authorizing amendments in writing executed by duly authorized officials of both
parties:

NOW, THEREFORE, in consideration of the mutual promises contained herein and
other good and valuable consideration, the receipt and adequacy of which is
hereby acknowledged, the parties hereto promise and agree as follows:

        1.  The University will use its best efforts to perform the research as
            described in Exhibit A for the period of October 1, 1999 through
            September 30, 2000.
<PAGE>

Janet Rideout, PH.D.                 2                         February 10, 2000

        2.  Sponsor shall pay the University during the term of the Amendment
            for all direct and indirect costs incurred by the University in
            connection with the Research, described in Exhibit A, in the amount
            not to exceed [CONFIDENTIAL TREATMENT REQUESTED]. Payment shall be
            made in accordance with the following schedule: one half (1/2) of
            the [CONFIDENTIAL TREATMENT REQUESTED] supplement shall be made upon
            the execution of this Amendment, with the balance to be paid upon
            submission of the Final Report. Budget attached as Exhibit B.

        3.   Any and all provisions of the Agreement not expressly modified
             hereby will remain in full force and effect.

IN WITNESS THEREOF, the undersigned duly authorized representatives of the
parties have executed this first amendment.

Inspire Pharmaceuticals, Inc.                  University of North Carolina
                                               At Chapel Hill

By:    /s/ Janet L. Rideout        By:       /s/ Robert P. Lowman
     --------------------------        -----------------------------------------

Name:   Janet L. Rideout           Name:     Robert P. Lowman, Ph.D.
      -------------------------          ---------------------------------------

Title:     V.P., Development       Title:  Director, Office of Research Services
       ------------------------           --------------------------------------

Date:     2/15/00                   Date:    FEB 17 2000
       ------------------------           --------------------------------------

                                    Principal Investigator
                                    ----------------------

                                     /s/ M. Jackson Stutts
                                    ----------------------

                                    Date:   2-17-00
                                          ----------------<PAGE>

                                                                    Exhibit 10.6

[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.]

                            CLINICAL TRIAL AGREEMENT

     This Agreement is entered into as of March 10, 1995 (the "Effective Date")
by and between The University of North Carolina at Chapel Hill (the
"University") and Inspire Pharmaceuticals, Inc. (the "Company"), a Delaware
corporation.

     1.  Performance of Study.  The University and the Company shall promptly
         --------------------
select a Principal Investigator who shall conduct a clinical study entitled
"Evaluation of UTP for the Treatment of Certain Chronic Airway Diseases" in
accordance with the work plan set forth on Exhibit A (the "Study"). In the event
                                           ---------
of any conflict between Exhibit A and the provisions of this Agreement, the
                        ---------
terms of this Agreement shall govern. In the event the Principal Investigator
becomes unwilling or unable to perform the duties required by this Agreement,
the parties shall attempt to find a mutually acceptable replacement, and if such
replacement is not found within thirty (30) days, the Company may terminate this
Agreement immediately upon written notice to the University.

     2.  Payment for Study.  In consideration of the performance of the Study,
         -----------------
the Company shall pay the University in accordance with the budget and payment
schedule set forth on Exhibit B (the "Budget").  All checks shall be made
                      ---------
payable to The University of North Carolina at Chapel Hill and mailed to the
following address:

     S. Kent Walker
     University of North Carolina at Chapel Hill
     Office of Contracts and Grants
     440 West Franklin Street
     Chapel Hill, NC 27599

     3.  Inspection and Records.  The Principal Investigator shall furnish the
         ----------------------
Company with any results of the Study in signed case report forms within a
reasonable time after completion of each case, and the Company shall have the
unrestricted right, consistent with this Agreement, to use such Study results.
The University and the Principal Investigator agree to permit authorized
representatives of the Company to examine University facilities, validate case
reports against original results in University files, and monitor the work
performed for the Study, all at reasonable times during the term of this
Agreement, for the purpose of determining the adequacy of the facilities and
whether the study is being conducted in compliance with the work plan set forth
on Exhibit A  and with relevant U.S. Food and Drug Administration ("FDA")
   ----------
regulations.  Records of the Study (specifically including a copy of all
volunteer consent forms) shall be retained in conformance with applicable
federal regulations.  The Company shall notify the Principal Investigator of the
date a new drug application ("NDA") is approved for the drug under study; or if
the NDA is not approved, the Company shall notify the Principal Investigator
when all clinical investigations have been discontinued and the FDA has been
notified.  The University will promptly notify the Company, by telephone and
subsequently in written form, of any significant changes that occur at any time
during the Study, including without limitation any adverse events or changes to
the personnel conducting the Study.
<PAGE>

  4.  Compliance with Law.  The Principal Investigator shall conduct the Study
      -------------------
at the University with the prior approval and ongoing review of all necessary
and appropriate authorities, including without limitation the University
Institutional Review Board, and in compliance with all federal, state, and local
laws and regulations.  At the request of the Company, the Principal Investigator
shall provide written evidence of all Institutional Review Board approvals.

     5.  Intellectual Property.  Neither the Company nor the University
         ---------------------
transfers to the other any patent right, copyright, or other proprietary right
owned by such party as of the Effective Date.  The University agrees that any
inventions, discoveries, or improvements arising out of the Study ("Inventions")
shall be promptly disclosed by the University to the Company.  The University
hereby grants to the Company a first option to obtain an exclusive, worldwide
license to make, have made, use, and sell products incorporating such
Inventions.  The Company may exercise its option by written notice to the
University which is received within ninety (90) days after the Company receives
written disclosure of an Invention from the University.  During this option
period, the University shall provide the Company with any information reasonably
necessary for evaluating the subject Invention.  In the event that the Company
exercises its license option, the parties shall negotiate in good faith a
license agreement on commercially reasonable terms and conditions.  If the
parties cannot reach agreement within ninety (90) days after the Company
exercised its license option, or if the Company fails to exercise its option
right within the specified option period, the University shall thereafter be
free to license such Invention to third parties.  The University reserves the
right to use the results of the study for its own noncommercial, academic
purposes.

     6.  Confidentiality.  The University agrees not to disclose to any third
         ---------------
party or to use for any purposes other than performance of the Study any and all
trade secrets, privileged records, or other proprietary information (hereinafter
"Information") obtained by the University under this Agreement.  Any Information
disclosed to the University by the Company shall be designated as "Confidential"
in writing.  Such information shall be disclosed only to the Principal
Investigator and persons working on the Study under the direction of the
Principal Investigator, subject to the confidentiality terms of this Agreement.
The obligation of non-disclosure and non-use shall extend for a period of three
(3) years upon execution of this Agreement and shall not apply to the following:

     (a)  Information at or after such time that it is or becomes publicly
          available through no fault of the University;

     (b)  Information which is disclosed to the University by a third party who
          is under no obligation of confidence with respect to such information;

     (c)  Information which is already known to the University as shown by its
          prior written records, provided that the University so demonstrates to
          the Company within fifteen (15) days after disclosure of the
          Information to the University by the Company;
<PAGE>

     (d)  Information that is developed by the University, independent of the
          disclosure of Information by the Company, as demonstrated by
          documentary evidence.

     (e)  Information that is required to be disclosed to comply with applicable
          laws or regulations, or with a court or administrative order, provided
          that the University gives the Company prior written notice of such
          disclosure and that the University takes all reasonable and lawful
          actions to obtain confidential treatment for such disclosure and, if
          possible, to minimize the extent of such disclosure.

At the conclusion of the study, the University shall return all such Information
to the Company.

     7.  Publication.  In order to prevent the inadvertent loss of patent rights
         -----------
or disclosure of confidential information, the University shall provide the
Company, for review by the Company, with pre-prints or abstracts of any proposed
presentation or paper describing any results of the Study at least sixty (60)
days prior to publication.  At the conclusion of this sixty-day review period,
the University shall be free to proceed with publication.

     8.  Term and Expiration.  This Agreement shall commence on the Effective
         -------------------
Date and shall continue for a period of one (1) year, unless sooner terminated
as provided below.  The parties may extend the term of this Agreement for
additional six (6) month periods by mutual written agreement.  Sections 3, 5, 6,
7, l3, and 16 shall survive termination of this Agreement.

     9.  Early Termination.  This Agreement may be terminated at any time by
         -----------------
either the University or the Company for any reason upon (30) days prior written
notice to the other party, whereupon the University will use its best efforts
immediately to curtail charges and make no subsequent commitments for
expenditures under this Agreement.  In the event of termination when there is an
outstanding balance of funds owed to the University pursuant to Section 2 above,
including any University uncancellable commitments, the Company shall make a
final payment for services performed under the terms of this Agreement through
the date of termination.  In the event of termination when the University
possesses prepaid funds that the University has not earned as of the date of
termination, the University shall promptly remit such funds to the Company.

     10.  Independent Contractors.  Each party to this Agreement shall act as an
          -----------------------
independent contractor and shall not act as the agent, employee, or servant of
any other party.  Accordingly, the employees of the University shall not be
considered the employees of the Company, and no party shall enter into any
contract or agreement with a third party which purports to obligate or bind any
other party.

     11.  Changes to the Study.  If at a future date changes in the Study appear
          --------------------
desirable, such changes may be  made through prior agreement between the Company
and University.  If such changes can be expected to affect the charge for the
Study, University will submit a written estimate for approval to Company.
However, if in the course of
<PAGE>

performing this Agreement, generally accepted standards of clinical research and
medical practice relating to the benefit, well-being, and safety of the
patient(s) requires a deviation from the study, such standards will be followed.
In such case, the party aware of the need for a deviation shall immediately
inform the other parties of the circumstances giving rise to such need.

     12.  Title to Equipment.  Title to all equipment purchased by the
          ------------------
University for use in performing this Agreement shall be in the University and
shall be free of all claims, liens, or encumbrances of the Company, or anyone
claiming under or through the Company.

     13.  Return of Materials.  Upon the earlier of the completion of the Study
          -------------------
or the termination of this Agreement, all unused compounds, materials, or
supplies that were furnished to the University by the Company or purchased by
the University using funds provided by the Company shall be promptly returned to
Company, at the Company's expense.

     14.  Assignment.  This Agreement may not be assigned by either party
          ----------
without the prior written consent of the other party, except that the Company
may assign this Agreement to an affiliate or to a successor in connection with
the merger, consolidation, or sale of all or substantially all of its assets or
that portion of its business pertaining to the subject matter of this Agreement.

     15.  Use of University Name.  No press release, advertising, promotional
          ----------------------
sales literature, or other promotional written statements or promotional oral
statements to the public in connection with or alluding to work performed under
this Agreement or the relationship between the parties created by it, having or
containing any reference to the Company or the University, shall be made by any
party without the prior written approval of the affected party.  The foregoing
notwithstanding, the Company shall have the right to identify the University and
to disclose the terms of this agreement in any prospectus, offering memorandum,
or other document or filing required by applicable securities laws or other
applicable law or regulation.

     16.  Indemnification.  The Company hereby agrees to indemnify, defend, and
          ---------------
hold harmless the University and its schools, departments, and employees from
and against any and all liability arising out of the performance of this Study,
provided that (i) the Study is performed in compliance with this agreement and
the protocol set forth on Exhibit A, (ii) such liability does not arise out of
                          ---------
the negligence or willful misconduct of the University or its employees or
agents, (iii) the Company is promptly notified of any complaint, claim, or
injury to any subject that arises out of or in connection with the performance
of the Study, and (iv) subject to the statutory duty of the Attorney General of
the State of North Carolina, the Company has sole control of the defense or
settlement of any such complaint or claim.

     To the extent provided by the North Carolina Tort Claims Act, the
University agrees to indemnify, defend, and hold harmless the Company and its
directors, officers, employees, and agents against all losses, expenses, claims,
demands, suits, or other actions that arise out of or in connection with the
performance of the Study to the extent resulting from the negligence or willful
misconduct of the University or its employees or agents.
<PAGE>

  17.  Notices.  All notices, requests, demands, and other communications
       -------
required or permitted to be given pursuant to this Agreement shall be in writing
and shall be deemed to have been duly given (i) upon the date of receipt if
delivered by hand, recognized national overnight courier, confirmed facsimile
transmission, or registered or certified mail, return receipt requested, postage
prepaid, or (ii) on the third business day after mailing by first class mail,
postage prepaid, to the following addresses or facsimile numbers:

     If to the Company:

     H. Jeff Leighton, Ph.D.
     President and Chief Executive Officer
     Inspire Pharmaceuticals, Inc.
     c/o Burr, Egan, Deleage & Co.
     One Post Office Square
     Boston, MA 02110
     Tel:  (617) 482-8020
     Fax:  (617) 566-0848

     With a copy to:

     Michael Lytton, Esq.
     Palmer & Dodge
     One Beacon Street
     Boston, MA 02108
     Fax:  (617) 227-4420

     If to the University:

     Dr. Robert P. Lowman
     Office of Research Services
     University of North Carolina at Chapel Hill
     CB# 4100, 300 Bynum Hall
     Chapel Hill, NC 27599
     Tel:  (919) 966-5265
     Fax:  (919) 962-0646

Either party may change its designated address and facsimile number by notice to
the other party in the manner provided in this Section.

     18.  Choice of Law.  The laws of the State of North Carolina shall govern
          -------------
the validity and interpretation of the provisions, terms, and conditions of the
Agreement.

     19.  Waiver.  Failure to insist upon compliance with any of the terms and
          ------
conditions of this Agreement shall not constitute a general waiver or
relinquishment of any such terms or conditions, but the same shall remain at all
time in full force and effect.
<PAGE>

     20.  Severability.  In the event that any provision of this Agreement
          ------------
shall, for any reason, be held to be invalid or unenforceable in any respect,
such invalidity or unenforceability shall not affect any other provision hereof,
and this Agreement shall be construed as if such invalid or unenforceable
provision had not been included herein.

     21.  Entire Agreement and Modification.  This Agreement contains the entire
          ---------------------------------
understanding of both parties and shall not be altered, amended or modified
except by an agreement in writing executed by the duly authorized officials of
both parties.

AGREED AND ACCEPTED:

INSPIRE PHARMACEUTICALS, INC.           UNIVERSITY OF NORTH CAROLINA
                                        AT CHAPEL HILL

    /s/ H. Jeff Leighton                  /s/ Wayne R. Jones
--------------------------------  ------------------------------------
H. Jeff Leighton                          Wayne R. Jones
President                                 Vice Chancellor, Business & Finance
<PAGE>

                                   Exhibit A

                                   Work Plan
                                   ---------

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                                   Exhibit B

                                     Budget
                                     ------

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                          ADDENDUM TO AMENDMENT # 95-1

This ADDENDUM, made and entered into this 19th day of July, 1996, by and between
The University of North Carolina at Chapel Hill, hereinafter referred to as the
"University" and Inspire Pharmaceuticals, Inc., hereinafter referred to as the
"Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of Certain
Chronic Airway Diseases," hereinafter referred to as the "Agreement"; and

WHEREAS, the parties wish by this ADDENDUM to revise the specific terms of an
individual research project, hereinafter referred to as the "Project," as
contemplated by Exhibit A, #2a, of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1.  Article 1, Performance of Study shall be amended as follows:
               --------------------

The University shall exercise its best efforts to carry out the Project set
forth in the Protocol with the revised title of "Acute Safety Study of UTP in
Patients with COPD" and attached here as Attachment A-1 ("Protocol") in
accordance with the Agreement.  The University's Principal Investigator for this
Project is M. Patricia Rivera, M.D., who will be responsible for the direction
of this Project.  To the extent the terms of Attachment A conflict with the
terms of this ADDENDUM, the Agreement, and Amendment #95-1, the terms this
ADDENDUM, the Agreement and Amendment #95-1 shall govern the conduct of the
parties.

2.  Article 2, Payment for Study for the research to be conducted under this
               -----------------
ADDENDUM to Amendment #95-1 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University in accordance with the budget set forth in Attachment B-1, attached
hereto and made a part hereof..  An initial payment of [CONFIDENTIAL TREATMENT
REQUESTED] will be made upon execution of this ADDENDUM   and includes the
direct and indirect costs for one patient ([CONFIDENTIAL TREATMENT REQUESTED])
and equipment (Passport Monitor @[CONFIDENTIAL TREATMENT REQUESTED]).
Subsequent payments of [CONFIDENTIAL TREATMENT REQUESTED] will be made upon the
completion of each patient in accordance with the Protocol and acceptance of the
case report form.  Payments for partially completed patients shall be prorated
according to the assessments completed.  All checks shall be made payable to the
University of North Carolina at Chapel Hill and mailed to the following address:

     M. Patricia Rivera, M.D.
     Department of Pulmonary Medicine
     CB#7020 - 724 Burnett-Womack Bldg.
     Chapel Hill, NC 27599-7220
<PAGE>

3.  All terms of the Agreement and Amendment 95-1 not altered by this ADDENDUM
shall remain in full force and effect throughout the term of said agreement.

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.
<TABLE>
<CAPTION>
FOR AND ON BEHALF OF                                   FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.                          UNIVERSITY OF NORTH
                                                       CAROLINA AT CHAPEL HILL
<S>                                                    <C>
/s/  David J. Drutz
---------------------------------------------
Signature
                                                         /s/  Wayne R. Jones
                                                       ----------------------------------------------
                                                         Signature

David J. Drutz, M.D.
---------------------------------------------
Name
                                                         Wayne R. Jones
                                                       ----------------------------------------------
                                                         Name

President and CEO
---------------------------------------------
Title
                                                         Vice Chancellor, Business & Finance
                                                       ----------------------------------------------
                                                         Title

Date:      June 21, 1996                                 Date:      7/19/96
         ------------------------------------                     -----------------------------------
</TABLE>

Agreed and Accepted:  /s/ M. Patricia Rivera
                      ----------------------
                      Principal Investigator

     Date:     July 10, 1996
            ----------------
<PAGE>

                                ATTACHMENT A-1

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                                ATTACHMENT B-1

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                AMENDMENT #95-2

This Amendment, made and entered into this 4th day of December, 1995, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of Certain
Chronic Airway Diseases," hereinafter referred to as the "Agreement"; and

WHEREAS, the parties wish by this Amendment to specify terms of an individual
research project, hereinafter referred to as the "Project," as contemplated by
Exhibit A, #3c, of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1.  Article 1, Performance of Study shall be amended as follows:
               --------------------

The University shall exercise its best efforts to carry out the Project set
forth in the Protocol entitled:  "Acute Safety of UTP-Amiloride Aerosol in
Children Ages 4-10 Years" and attached here as Attachment A ("Protocol") in
accordance with the Agreement.  The University's Principal Investigator for this
Project is George Retsch-Bogard, M.D., who will be responsible for the direction
of this Project.  The parties anticipate that the term of this Project will be
from the date of execution through March 9, 1996.  To the extent the terms of
Attachment A conflict with the terms of the Agreement or this Amendment #95-2,
the terms of the Agreement and this Amendment # 95-2 shall govern the conduct of
the parties.

2.  Article 2, Payment for Study for the research to be conducted under this
               -----------------
Amendment #95-2 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University [CONFIDENTIAL TREATMENT REQUESTED]in accordance with the budget set
forth in Attachment B, attached hereto and made a part hereof..  An initial
payment of [CONFIDENTIAL TREATMENT REQUESTED] will be made upon execution of
this Amendment and includes the direct and indirect costs for one patient
([CONFIDENTIAL TREATMENT REQUESTED]) and for the repair, upgrade, and
maintenance of equipment ([CONFIDENTIAL TREATMENT REQUESTED]).  Subsequent
payments of [CONFIDENTIAL TREATMENT REQUESTED] will be made upon the completion
of each patient in accordance with the Protocol and acceptance of the case
report form.  All checks shall be made payable to the University of North
Carolina at Chapel Hill and mailed to the following address:

     George Retsch-Bogart, M.D.
     Department of Pediatrics
     CB#7220 - Burnett-Womack Bldg.
     Chapel Hill, NC 27599-7220
<PAGE>

3.  All terms of the Agreement not altered by this Amendment shall remain in
full force and effect throughout the term of said agreement

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

FOR AND ON BEHALF OF                       FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.              UNIVERSITY OF NORTH
                                           CAROLINA AT CHAPEL HILL

/s/ H. Jeff Leighton                       /s/ Robert P. Lowman
-------------------------------------      -------------------------------------
Signature                                  Signature

    H. Jeff Leighton                       Robert P. Lowman, Ph.D.
-------------------------------------      -------------------------------------
Name                                       Name

Managing Director                          Director, Office of Research Services
-------------------------------------      -------------------------------------
Title                                      Title

Date:            1--22-95                  Date:           DEC 04 1995
         ----------------------------               ----------------------------

Agreed and Accepted:  /s/ George Retsch-Bogart, M.D.
                      ------------------------------
                      Principal Investigator

                      Date:   11-6-95
                             -----------------------
<PAGE>

                                  ATTACHMENT A

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                                  ATTACHMENT B

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                          ADDENDUM TO AMENDMENT # 95-2

This ADDENDUM, made and entered into this 11 day of March, 1996, by and between
The University of North Carolina at Chapel Hill, hereinafter referred to as the
"University" and Inspire Pharmaceuticals, Inc., hereinafter referred to as the
"Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of Certain
Chronic Airway Diseases,"hereinafter referred to as the "Agreement"; and

WHEREAS, the parties wish by this Addendum to revise the specific terms of an
individual research project, hereinafter referred to as the "Project," as
contemplated by Exhibit A, #3c, of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1.  See * below.
2.  Article 2, Payment for Study for the research to be conducted under
               -----------------
Amendment #95-2 shall be replaced as follows:

In consideration of the performance of this Project, the Company shall pay the
University up to [CONFIDENTIAL TREATMENT REQUESTED] in accordance with the
budget set forth in Attachment B, attached hereto and made part hereof..  An
initial payment of [CONFIDENTIAL TREATMENT REQUESTED] will be made upon
execution of this Addendum and includes the direct and indirect costs for one
patient ([CONFIDENTIAL TREATMENT REQUESTED]) and for the repair, upgrade, and
maintenance of equipment ([CONFIDENTIAL TREATMENT REQUESTED]).  Subsequent
payments of [CONFIDENTIAL TREATMENT REQUESTED] will be made upon the completion
of patients 2-4 in accordance with the original Protocol and acceptance of the
case report forms.  Payments of [CONFIDENTIAL TREATMENT REQUESTED] will be made
upon the completion of patients 5-10 in accordance with the Protocol as revised
and acceptance of the case reports form.  All checks shall be made payable to
the University of North Carolina at Chapel Hill and mailed to the following
address:

     George Retsch-Bogart, M.D.
     Department of Pediatrics
     CB#7220 - Burnett-Womack Bldg.
     Chapel Hill, NC 27599-7220

*    The University shall exercise its best efforts to carry out the Study set
     forth in Amendment 1 to the Protocol entitled "Acute Safety of Aerosolized
     UTP (with and with- out amiloride) in Children (age 4-10 years) with Cystic
     Fibrosis" and attached here as Attachment A-1 ("Protocol") in accordance
     with the Agreement.
<PAGE>

3.  All terms of Amendment 95-2 not altered by this Addendum shall remain in
full force and effect throughout the term of said agreement.

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

<TABLE>
<CAPTION>
FOR AND ON BEHALF OF                                     FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.                            UNIVERSITY OF NORTH
                                                         CAROLINA AT CHAPEL HILL
<S>                                                    <C>

/s/  David J. Drutz, M.D.                                /s/  Robert P. Lowman
---------------------------------------------          ----------------------------------------------
Signature                                                Signature

David J. Drutz                                           Robert P. Lowman, Ph.D.
---------------------------------------------          ----------------------------------------------
Name                                                     Name

President and CEO                                        Director, Office of Research Services
---------------------------------------------          ----------------------------------------------
Title                                                    Title

Date:      March 12, 1996                                Date:      APR 23 1996
         ------------------------------------                     -----------------------------------
</TABLE>

Agreed and Accepted:  /s/ George Retsch-Bogart, M.D.
                      ------------------------------
                      Principal Investigator

                      Date:     4-16-96
                              -----------
<PAGE>

                                ATTACHMENT A-1

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                               PROTOCOL AMENDMENT

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                                  ATTACHMENT B

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                AMENDMENT #95-3

This Amendment, made and entered into this day of, 3/11/96, by and between The
University of North Carolina at Chapel Hill, hereinafter referred to as the
"University" and Inspire Pharmaceuticals, Inc., hereinafter referred to as the
Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of Certain
Chronic Airway Diseases," hereinafter referred to as the "Agreement"; and

WHEREAS, the parties wish by this Amendment to specify terms of an individual
research project, hereinafter referred to as the "Project," as contemplated by
Exhibit A, #3b, of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1.  Article 1, Performance of Study shall be amended as follows:
               --------------------

The University shall exercise its best efforts to carry out the Project set
forth in the Protocol entitled:  "Acute Efficacy of UTP-Amiloride Aerosol in
Adolescents Ages 11-18 Years" and attached here as Attachment A ("Protocol") in
accordance with the Agreement The University's Principal Investigator for this
Project is George Retsch-Bogard, M.D., who will be responsible for the direction
of this Project.  To the extent the terms of Attachment A conflict with the
terms of the Agreement or this Amendment #95-3, the terms of the Agreement and
this Amendment #95-3 shall govern the conduct of the parties.

2.  Article 2, Payment for Study for the research to be conducted under this
               -----------------
Amendment #95-3 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University up to [CONFIDENTIAL TREATMENT REQUESTED] in accordance with the
budget set forth in Attachment B, attached hereto and made a part hereof.  An
initial payment of [CONFIDENTIAL TREATMENT REQUESTED] will be made upon
execution of this Amendment and includes the direct and indirect costs for one
patient ([CONFIDENTIAL TREATMENT REQUESTED]) and for the repair, upgrade, and
maintenance of equipment ([CONFIDENTIAL TREATMENT REQUESTED]).  Subsequent
payments of [CONFIDENTIAL TREATMENT REQUESTED] will be made upon the completion
of each patient in accordance with the Protocol and acceptance of the case
report form.  All checks shall be made payable to the University of North
Carolina at Chapel Hill and mailed to the following address:

     George Retsch-Bogart, M.D.
     Department of Pediatrics
     CB#7220 - Burnett-Womack Bldg.
     Chapel Hill, NC 27599-7220
<PAGE>

3.  All terms of the Agreement not altered by this Amendment shall remain in
full force and effect throughout the term of said agreement

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

FOR AND ON BEHALF OF                       FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.              UNIVERSITY OF NORTH
                                           CAROLINA AT CHAPEL HILL

/s/ David J. Drutz                         /s/ Robert P. Lowman
-------------------------------------      -------------------------------------
Signature                                  Signature

      David J. Drutz, M.D.                 Robert P. Lowman, Ph.D.
-------------------------------------      -------------------------------------
Name                                       Name

       President and CEO                   Director, Office of Research Services
-------------------------------------      -------------------------------------
Title                                      Title

           March 12, 1996                             MAR 26 1996
-------------------------------------      -------------------------------------
Date:                                      Date:

Agreed and Accepted:  /s/ George Retsch-Bogart
                      ---------------------------
                      Principal Investigator

               Date:   3-21-96
                     ------------------
<PAGE>

                                  ATTACHMENT A

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                                  ATTACHMENT B

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                AMENDMENT # 95-4

This ADDENDUM, made and entered into this 21st day of March , 1996, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of Certain
Chronic Airway Diseases,"hereinafter referred to as the "Agreement"; and

WHEREAS, the parties wish by this Amendment to specify terms of an individual
research project, hereinafter referred to as the "Project," as contemplated by
Exhibit A, #2, of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1.  Article 1, Performance of Study shall be amended as follows:
               --------------------

The University shall exercise its best efforts to carry out the Project set
forth in the Protocol entitled: "Acute Efficacy of Aerosolized UTP-Amiloride by
Mucocioliary and Cough Clearance in Patients with Primary Ciliary Dyskinesia
(PCD)" and attached here as Attachment A ("Protocol") in accordance with the
Agreement.  The University's Principal Investigator for this Project is Peadar
G. Noone, M.D., who will be responsible for the direction of this Project.  To
the extent the terms of Attachment A conflict with the terms of the Agreement or
this Amendment #95-4, the terms of the Agreement and this Amendment #95-4 shall
govern the conduct of the parties.

2.  Article 2, Payment for Study for the research to be conducted under this
               -----------------
Amendment #95-4 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University up to [CONFIDENTIAL TREATMENT REQUESTED] in accordance with the
budget set forth in Attachment B, attached hereto and made a part hereof.  An
initial payment of [CONFIDENTIAL TREATMENT REQUESTED] will be made upon
execution of this Amendment.  Subsequent payments of [CONFIDENTIAL TREATMENT
REQUESTED] will be made upon the completion of each patient in accordance with
the Protocol and acceptance of the case report form.  All checks shall be made
payable to the University of North Carolina at Chapel Hill and mailed to the
following address:

     Peadar Noone, M.D.
     Division of Pulonary Medicine
     University of North Carolina at Chapel Hill
     724 Burnett-Womack, CB# 7020
     Chapel Hill, NC 27599-7020
<PAGE>

3.  All terms of the Agreement not altered by this Amendment shall remain in
full force and effect throughout the term of said agreement

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

<TABLE>
<CAPTION>
FOR AND ON BEHALF OF                                     FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.                            UNIVERSITY OF NORTH
                                                         CAROLINA AT CHAPEL HILL
<S>                                                    <C>
/s/  David J. Drutz, M.D.
---------------------------------------------
Signature
                                                         /s/  Robert P. Lowman
                                                       ----------------------------------------------
                                                         Signature

David J. Drutz
---------------------------------------------
Name
                                                         Robert P. Lowman, Ph.D.
                                                       ----------------------------------------------
                                                         Name

President and CEO
---------------------------------------------
Title
                                                         Director, Office of Research Services
                                                       ----------------------------------------------
                                                         Title

Date:      March 21, 1996                                Date:      APR 12 1996
         ------------------------------------                     -----------------------------------
</TABLE>

Agreed and Accepted:  /s/  Peadar Noone
                      ---------------------
                      Principal Investigator

     Date:     April 2 '96
            ----------------
<PAGE>

                                  ATTACHMENT A

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                                  ATTACHMENT B

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                AMENDMENT # 95-5

This Amendment, made and entered into this 2nd day of October, 1996, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of Certain
Chronic Airway Diseases," hereinafter referred to as the "Agreement"; and

WHEREAS, The parties wish by this Amendment to specify terms of an individual
research project, hereinafter referred to as the "Project," as contemplated by
Exhibit A of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1.  Article 1, Performance of Study shall be amended as follows:
               --------------------

The University shall exercise its best efforts to carry out the Project set
forth in the Portocol entitled:  "Evaluation of Aerosol Delivery Systems for UTP
(Part 1)" and attached here as Attachment A ("Protocol") in accordance with the
Agreement.  The University's Principal Investigator for this Project is William
Bennett, Ph.D, who will be responsible for the direction of this Project.  To
the extent the terms of Attachment A conflict with the terms of the Agreement or
this Amendment #95-5, the terms of the Agreement and this Amendment #95-5 shall
govern the conduct of the parties.

2.  Article 2, Payment for Study for the research to be conducted under this
               -----------------
Amendment #95-5 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University [CONFIDENTIAL TREATMENT REQUESTED]  in accordance with the budget set
forth in Attachment B, attached hereto and made a part herof.  The University
acknowledges receipt of the initial payment of [CONFIDENTIAL TREATMENT
REQUESTED] .  Subsequent payments of [CONFIDENTIAL TREATMENT REQUESTED] shall be
made upon the completion Part A, Particle Sizing; [CONFIDENTIAL TREATMENT
REQUESTED] shall be paid upon completion of Part B, Nebulizer Output, and
[CONFIDENTIAL TREATMENT REQUESTED] shall be paid upon submission to Inspire of
all data and a brief summary report.  All checks shall be made payable to the
University of North Carolina at Chapel Hill and mailed to the following address:

  William Bennett
  Center for Environmental Medicine
  University of North Carolina at Chapel Hill
  104 Mason Farm Road, CB# 7310
  Chapel Hill, NC 27599-7310
<PAGE>

3.  All terms of the Agreement not altered by this Amendment shall remain in
full force and effect throughout the term of said agreement

  IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
  official capacities of the day and year listed below.

<TABLE>
<CAPTION>
FOR AND ON BEHALF OF                                             FOR AND ON BEHALF
INSPIRE PHARMACUETICALS, INC.                                    OF THE UNIVERSITY OF NORTH
                                                                 CAROLINA AT CHAPEL HILL
<S>                                                           <C>
/s/ David J. Drutz
---------------------------------------------
Signature                                                        /s/  Robert P. Lowman
                                                               ----------------------------------------------
                                                                 Signature

David J. Drutz, MD
---------------------------------------------
Name                                                             Robert P. Lowman, Ph.D.
                                                               ----------------------------------------------
                                                                 Name

President & CEO
---------------------------------------------
Title                                                            Director, Office of Research Services
                                                               ----------------------------------------------
                                                                 Title

Date:     9/10/96                                                Date:           OCT 02 1996
---------------------------------------------                    --------------------------------------------
</TABLE>

Agreed and Accepted:         /s/  William D. Bennett
                           -----------------------------------------------------
                             Principal Investigator

                             Date:    9/17/96
                           -----------------------------------------
<PAGE>

                                   EXHIBIT A
                                   ---------

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                AMENDMENT # 95-6

This Amendment, made and entered into this 15 day of November, 1996, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTPfor the Treatment of Certain Chronic
Airway Diseases," hereinafter referred to as the "Agreement"; and

WHEREAS, The parties wish by this Amendment to specify terms of an individual
research project, hereinafter referred to as the "Project," as contemplated by
Exhibit A of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

4.  Article 1, Performance of Study shall be amended as follows:
               --------------------

The University shall exercise its best efforts to carry out the Project set
forth in the Protocol entitled: "Rising Dose Tolerance Study of Multiple Daily
Doses of Uridine 5'-Triphosphate in Patients with Mild to Moderate Cystic
Fibrosis Lung Disease" and attached here as Attachment A ("Protocol") in
accordance with the Agreement.  The University's Principal Investigator for this
Project is Dr. Peader Noone, who will be responsible for the direction of this
Project.  To the extent the terms of Attachment A conflict with the terms of the
Agreement or this Amendment #95-6, the terms of the Agreement and this Amendment
#95-6 shall govern the conduct of the parties.

5.  Article 2, Payment for Study for the research to be conducted under this
               -----------------
Amendment #95-6 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University up to [CONFIDENTIAL TREATMENT REQUESTED] in accordance with the
budget set forth in Attachment B, attached hereto and made a part hereof.  The
University acknowledges receipt of an initial payment of [CONFIDENTIAL TREATMENT
REQUESTED], representing the cost for two completed patients.  Subsequent
payments shall be made upon completion of case report forms and their review by
Company.  The final payment shall be made upon completion of case report forms
and their acceptance by Company.  All checks shall be made payable to the
University of North Carolina at Chapel Hill and mailed to the following address:

  Dr. Peadar Noone
  Division of Pulmonary Medicine
  University of North Carolina at Chapel Hill
  724 Burnett-Womack, CB# 7020
  Chapel Hill, NC  27599-7020
<PAGE>

3.  All terms of the Agreement not altered by this Amendment shall remain in
full force and effect throughout the term of said agreement

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

<TABLE>
<CAPTION>
FOR AND ON BEHALF OF                                             FOR AND ON BEHALF
INSPIRE PHARMACUETICALS, INC.                                    OF THE UNIVERSITY OF NORTH
                                                                 CAROLINA AT CHAPEL HILL
<S>                                                           <C>
/s/ David J. Drutz
---------------------------------------------
Signature                                                        /s/  Robert P. Lowman
                                                               ----------------------------------------------
                                                                 Signature

David J. Drutz, MD
---------------------------------------------
Name                                                             Robert P. Lowman, Ph.D.
                                                               ----------------------------------------------
                                                                 Name

President & CEO
---------------------------------------------
Title                                                            Director, Office of Research Services
                                                               ----------------------------------------------
                                                                 Title

Date:     January 28, 1997                                       Date:           MAR 14 1997
---------------------------------------------                    --------------------------------------------
</TABLE>

Agreed and Accepted:              /s/  Peader Noone
                                ------------------------------------------------
                                  Principal Investigator

                                  Date:    3/7/97
                                ------------------------------------------------
<PAGE>

                             ATTACHMENT A (Protocol)
                             -----------------------

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                AMENDMENT # 95-7

This Amendment, made and entered into this 1 day of January, 1997, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of Certain
Chronic Airway Diseases," hereinafter referred to as the "Agreement"; and

WHEREAS, The parties wish by this Amendment to specify terms of an individual
research project, hereinafter referred to as the "Project," as contemplated by
Exhibit A of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

6.  Article 1, Performance of Study shall be amended as follows:
               --------------------

The University shall exercise its best efforts to carry out the Project set
forth in the Protocol entitled: "A Safety and Tolerability Study of Aerosolized
Uridine 5'-Triphosphate (UTP) in Patients with Mild Chronic Bronchitis:  A
Double-Blind Crossover Evaluation" and attached here as Attachment A
("Protocol") in accordance with the Agreement.  The University's Principal
Investigator for this Project is Dr. James Donohue, who will be responsible for
the direction of this Project.  To the extent the terms of Attachment A conflict
with the terms of the Agreement or this Amendment #95-7, the terms of the
Agreement and this Amendment #95-7 shall govern the conduct of the parties.

7.  Article 2, Payment for Study for the research to be conducted under this
               -----------------
Amendment #95-7 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University up to [CONFIDENTIAL TREATMENT REQUESTED] in accordance with the
budget set forth in Attachment B, attached hereto and made a part hereof.  An
initial payment of [CONFIDENTIAL TREATMENT REQUESTED], representing the cost for
two completed patients, shall be made within two weeks following execution of
this Amendment.  Subsequent payments shall be made upon completion of case
report forms and their review by Company.  The final payment shall be made upon
completion of case report forms and their acceptance by Company.  All checks
shall be made payable to the University of North Carolina at Chapel Hill and
mailed to the following address:

  Dr. James Donohue
  Division of Pulmonary Medicine
  University of North Carolina at Chapel Hill
  724 Burnett-Womack, CB# 7020
  Chapel Hill, NC  27599-7020
<PAGE>

8.  All terms of the Agreement not altered by this Amendment shall remain in
full force and effect throughout the term of said agreement

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

<TABLE>
<CAPTION>
FOR AND ON BEHALF OF                                             FOR AND ON BEHALF
INSPIRE PHARMACUETICALS, INC.                                    OF THE UNIVERSITY OF NORTH
                                                                 CAROLINA AT CHAPEL HILL
<S>                                                           <C>
/s/ David J. Drutz
---------------------------------------------
Signature                                                        /s/  Robert P. Lowman
                                                               ----------------------------------------------
                                                                 Signature

David J. Drutz, M.D.
---------------------------------------------
Name                                                             Robert P. Lowman, Ph.D.
                                                               ----------------------------------------------
                                                                 Name

President & CEO
---------------------------------------------
Title                                                            Director, Office of Research Services
                                                               ----------------------------------------------
                                                                 Title

Date:     January 28, 1997                                       Date:           MAR 17 1997
---------------------------------------------                    --------------------------------------------
</TABLE>

Agreed and Accepted:              /s/ James P. Donohue
                                ------------------------------------------------
                                  Principal Investigator

                                  Date:    3/12/97
                                ---------------------------------------
<PAGE>

                                   EXHIBIT A

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                      AMENDMENT TO CLINICAL TRIAL AGREEMENT

        This Amendment is dated as of June 9, 1997 by and between The University
of North Carolina at Chapel Hill (the "University") and Inspire Pharmaceuticals,
Inc. (the "Company"). The University and the Company agree to amend the Clinical
Trial Agreement, effective March 10, 1995, as previously amended (the
"Agreement), as follows:

        1.      The name of the Agreement shall be changed to "Clinical Research
Agreement."

        2.      Pursuant to Section 8, the term of the Agreement shall be
extended to and including June 9, 1998. The last sentence of Section 8 is hereby
amended by adding the words "the expiration or" immediately after the word
"survive".

        3.      The name of the person and the address of the Company to whom
notices and other communications to the Company should be directed, as set forth
in Section 17, shall be changed to:

                David J. Drutz, M.D.
                President and Chief Executive Officer
                Inspire Pharmaceuticals, Inc.
                4222 Emperor Boulevard, Suite 470
                Durham, North Carolina  27703
                Phone: (919)  941-9777
                Fax:   (919)  941-9797

The name and address of a person to whom a copy shall be sent shall be deleted.

        4.      Exhibits A and B expressly acknowledge that as of the Effective
Date of the Agreement each is "in preliminary form" and will require "further
elaboration" and "revision", respectively. The University and the Company agree
that Section 1 and Exhibits A and B have never been further elaborated or
revised, are obsolete, and should be revised to include the clinical studies
already underway or already agreed to be placed, such additional studies as the
Company and the University may agree, and a budget and payment schedule for each
such study. Accordingly, the University and the Company agree that Sections 1
and 2 and Exhibits A and B in the Clinical Trial Agreement as originally
executed shall be deleted. The following shall be the new Sections 1 and 2:

        "1.     Performance of Studies.  (a) The University and the Company
shall promptly select a Principal Investigator to conduct each study that the
parties agree shall be conducted at the University. A definitive list of the
studies conducted at the University (whether completed or terminated prior to
completion) or which the parties have agreed to conduct at the University is set
forth in Exhibit A attached hereto and made part of this
<PAGE>

Agreement. This Agreement shall cover clinical studies, clinical support studies
(including, but not limited to, metabolism studies in human cells or human
blood) and other clinically related studies involving UTP and/or other
substances of interest to the Company which the parties have agreed or will
agree to conduct at the University. The term "Study" shall refer to each study
conducted by the University pursuant to this Agreement, and the term "Principal
Investigator" shall refer to each Principal Investigator selected pursuant to
this Agreement. A definitive listing of the maximum budget or other total
payment obligation of the Company for each Study is set forth in Exhibit B
attached hereto and made a part of the Agreement.

        (b)     The University and the Company shall execute a separate "Work
Order # _______ " each time they agree to conduct an additional Study pursuant
to this Agreement. Each such Work Order shall set forth (i) the name of the
Principal Investigator, (ii) the duration of such Study, (iii) payment schedules
and information and (iv) a detailed work plan (Attachment A) and maximum budget
(Attachment B) for such Study which shall be deemed to be added to Exhibits A
and B of this Agreement, respectively.

        (c)     In the event of any conflict between (i) any Amendment executed
heretofore or any Work Order referred to in paragraph (b) of this Section 1 and
(ii) the provisions of this Agreement (including, without limitation, Exhibits A
and B attached hereto and made a part of this Agreement), the terms of this
Agreement shall govern.

        (d)     In the event that any Principal Investigator becomes unwilling
or unable to perform the duties required by this Agreement, the parties shall
attempt to find a mutually acceptable replacement, and if such replacement is
not found within thirty (30) days, the Company may terminate this Agreement with
respect to such Study immediately upon written notice to the Unversity."

        "2.     Payment for Studies.  In consideration of the performance of
each Study, the Company shall pay the University in accordance with the budget
and payment schedule set forth in the respective Amendment and other pertinent
documents which have been executed or exchanged heretofore and any Work Order
and other pertinent documents which may be executed or exchanged hereafter. All
checks shall be made payable to The University of North Carolina at Chapel Hill
and mailed to the respective addresses set forth in each Amendment or Work
Order, as the case may be."

        The new Exhibits A and B are set forth in the Appendix to this Amendment
 to the Agreement and made a part of the Agreement. The respective Work Plans
 and detailed maximum budgets or other total payment obligations of the Company
 for each Study set forth in each of the Amendments and other pertinent
 documents executed or exchanged heretofore are incorporated by reference in the
 revised
<PAGE>

Exhibits.

        5.      Except as expressly provided in this Amendment to the Agreement,
all other terms and conditions of the Agreement shall continue in full force and
effect.

THE UNIVERSITY OF NORTH
CAROLINA AT CHAPEL HILL                       INSPIRE PHARMACEUTICALS, INC.

By:     /s/ Robert P. Lowman                  By:     /s/ David J. Drutz
        ------------------------                      -------------------------
Title:  Director Office of Research                   David J. Drutz, M.D.
        Services                              Title:  President and CEO

<PAGE>

                                   EXHIBIT A

                                LIST OF STUDIES

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                                   EXHIBIT B

                  MAXIMUM BUDGETS OR TOTAL PAYMENT OBLIGATIONS

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                AMENDMENT #95-8

This Amendment, made and entered into this 12 day of September, 1997, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of Certain
Chronic Airway Diseases," hereinafter referred to as the "Agreement"; and

WHEREAS, The parties wish by this Amendment to specify terms of an individual
research project, hereinafter referred to as the "Project," as contemplated by
Exhibit A of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

9. Article 1, Performance of Study shall be amended as follows:

The University shall exercise its best efforts to carry out the Project set
forth in the Protocol entitled: "Evaluation of the Acute Effect of Aerosolized
Uridine 5' Triphosphate (UTP) on Mucociliary Clearance in Patients with Mild
Chronic Bronchitis: A Double-Blind Three-Period Crossover Study of Normal Saline
(Placebo) Versus Two Doses of UTP and a No Treatment Baseline" - and attached
here as Attachment A ("Protocol") in accordance with the Agreement. The
University's Principal Investigator for this Project is Dr. William Bennett, who
will be responsible for the direction of this Project. To the extent the terms
of Attachment A conflict with the terms of the Agreement or this Amendment
#95-8, the terms of the Agreement and this Amendment #95-8 shall govern the
conduct of the parties.

10. Article 2, Payment for Study for the research to be conducted under this
Amendment #95-8 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University up to [CONFIDENTIAL TREATMENT REQUESTED] in accordance with the
budget set forth in Attachment B, attached hereto and made a part hereof. An
initial payment of [CONFIDENTIAL TREATMENT REQUESTED], representing the cost for
two completed patients, shall be made within two weeks following execution of
this Amendment. Subsequent payments shall be made upon completion of case report
forms and their review by Company. The final payment shall be made upon
completion of case report forms and their acceptance by Company. All checks
shall be made payable to the University of North Carolina at Chapel Hill and
mailed to the following address:
<PAGE>

     Dr. William Bennett, Ph.D
     Center for Environmental Medicine
     University of North Carolina at Chapel Hill
     104 Mason Farm Road, CB #7310
     Chapel Hill, NC 27599-7310

3. All terms of the Agreement not altered by this Amendment shall remain in full
force and effect throughout the term of said agreement

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

FOR AND ON BEHALF OF                     FOR AND ON BEHALF OF THE
INSPIRE PHARMACUETICALS, INC.            UNIVERSITY OF NORTH
                                         CAROLINA AT CHAPEL HILL

/s/ David J. Drutz                       /s/ Robert P. Lowman
-------------------------------          -------------------------------------
Signature                                Signature

David J. Drutz, MD                       Robert P. Lowman, Ph.D.
-------------------------------          -------------------------------------
Name                                     Name

President & CEO                          Director, Office of Research Services
-------------------------------          -------------------------------------
Title                                    Title

Date: September 5, 1997                  Date: SEP  12  1997
-------------------------------          -------------------------------------

Agreed and Accepted:    /s/  William D Bennett
                        ------------------------
                        Principal Investigator

                        Date: 9/8/97
                        ------------------------
<PAGE>

                                   EXHIBIT A

                               CLINICAL PROTOCOL

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                AMENDMENT #95-9

This Amendment, made and entered into this 11th day of December, 1997, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a Clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of Certain
Chronic Airway Diseases," hereinafter referred to as the "Agreement"; and

WHEREAS, The parties wish by this Amendment to specify terms of an individual
research project, hereinafter referred to as the "Project," as contemplated by
Exhibit A of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

11. Article 1, Performance of Study shall be amended as follows:

The University shall exercise its best efforts to carry out the Project set
forth in the Protocol entitled: "A Double-Blind, Two-Phase Safety Challenge of
the Acute Effects of Aerosolized Uridine 5'-Triphosphate (UTP) in Patients with
Mild Chronic Bronchitis: Influence of the Presence of Chloride Concentrations in
the Dosing Solutions" and attached here as Attachment A ("Protocol") in
accordance with the Agreement. The University's Principal Investigator for this
Project is Dr. James Donohue, who will be responsible for the direction of this
Project. To the extent the terms of Attachment A conflict with the terms of the
Agreement or this Amendment #95-9, the terms of the Agreement and this Amendment
#95-9 shall govern the conduct of the parties.

12. Article 2, Payment for Study for the research to be conducted under this
Amendment #95-9 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University up to [CONFIDENTIAL TREATMENT REQUESTED] in accordance with the
budget set forth in Attachment B, attached hereto and made a part hereof. An
initial payment of [CONFIDENTIAL TREATMENT REQUESTED], representing the cost for
one completed patient shall be made within two weeks following execution of this
Amendment. Subsequent payments shall be made upon completion of case report
forms and their review by Company. The final payment shall be made upon
completion of case report forms and their acceptance by Company.
<PAGE>

All checks shall be made payable to the University of North Carolina at Chapel
Hill and mailed to the following address:

     Dr. James Donohue
     Division of Pulmonary Medicine
     University of North Carolina at Chapel Hill
     724 Burnett-Womack, CB# 7020
     Chapel Hill, NC  27599-7020

3. All terms of the Agreement not altered by this Amendment shall remain in full
force and effect throughout the term of said agreement

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

FOR AND ON BEHALF OF                      FOR AND ON BEHALF OF THE
INSPIRE PHARMACUETICALS, INC.             UNIVERSITY OF NORTH
                                          CAROLINA AT CHAPEL HILL

/s/ David J. Drutz                        /s/ Robert P. Lowman
-------------------------------           -------------------------------------
Signature                                 Signature

David J. Drutz, MD                        Robert P. Lowman, Ph.D.
-------------------------------           -------------------------------------
Name                                      Name

President and CEO                         Director, Office of Research Services
-------------------------------           -------------------------------------
Title                                     Title

Date: November 25, 1997                   Date: DEC 11 1997
-------------------------------           -------------------------------------

Agreed and Accepted:    /s/  James F. Donohue
                        ------------------------
                        Principal Investigator

                        Date: 12/10/97
                        ------------------------
<PAGE>

STATE OF NORTH CAROLINA
COUNTY OF ORANGE

                                AMENDMENT #95-11

This Amendment, made and entered into this 1st day of August, 1998, by and
between The University of North Carolina at Chapel Hill, hereinafter referred to
as the "University" and Inspire Pharmaceuticals, Inc., hereinafter referred to
as the "Company".

                                  WITNESSETH:

WHEREAS, the parties previously entered in a clinical Trial Agreement dated
March 10, 1995 concerning "Evaluation of UTP for the Treatment of certain
Chronic Airway Diseases," hereinafter referred to as the "Agreement"; and

WHEREAS, the parties wish by this Amendment to specify terms of an individual
research project, hereinafter referred to as the "Project," as contemplated by
Exhibit A of the Agreement.

NOW, THEREFORE, in consideration of the premises and of the following mutual
promises, covenants, considerations and the sums to be paid, the University and
the Company agree as follows:

1. Article 1, Performance of Study shall be amended as follows:

The University shall exercise its best efforts to carry out the Project set
forth in the Protocol entitled: A Double-Blind Crossover Evaluation of the
Effect of Single Doses of Aerosolized INS365 Versus Normal Saline (Placebo) on
Mucociliary clearance in Normal Volunteers (Nonsmokers and Smokers)" and
attached here as Attachment A ("Protocol") in accordance with the Agreement. The
University's Principal Investigator for this Project is Dr. William Bennett, who
will be responsible for the direction of this Project. To the extent the terms
of Attachment A conflict with the terms of the Agreement or this Amendment
#95-11, the terms of the Agreement and this Amendment #95-11 shall govern the
conduct of the parties.

2. Article 2, Payment for Study for the research to be conducted under this
Amendment #95-11 shall be as follows:

In consideration of the performance of this Project, the Company shall pay the
University up to [CONFIDENTIAL TREATMENT REQUESTED] in accordance with the
budget set forth in Attachment B, attached hereto and made a part hereof. An
initial payment of [CONFIDENTIAL TREATMENT REQUESTED], representing the cost for
two completed patients, shall be made within two weeks following execution of
this Amendment. Subsequent payments shall be made upon completion of case report
forms and their review by Company. The final payment shall be made upon
completion of case report forms and their acceptance by Company.
<PAGE>

All Checks shall be made payable to the University of North Carolina at Chapel
Hill and mailed to the following address:

     William Bennett
     Center for Environmental Medicine
     University of North Carolina at Chapel Hill
     104 Mason Farm Road, CB# 7310
     Chapel Hill, NC 27599-7310

3. All terms of the Agreement not altered by this Amendment shall remain in full
force and effect throughout the term of said agreement.

IN WITNESS WHEREOF, the parties have hereunto signed this Agreement in their
official capacities of the day and year listed below.

FOR AND ON BEHALF OF                    FOR AND ON BEHALF OF THE
INSPIRE PHARMACEUTICALS, INC.           UNIVERSITY OF NORTH
                                        CAROLINA AT CHAPEL HILL

/s/ Christy L. Shaffer                  /s/ Robert P. Lowman
-------------------------------         -------------------------------------
Signature                               Signature

Christy L. Shaffer, Ph.D.               Robert P. Lowman, Ph.D.
-------------------------------         -------------------------------------
Name                                    Name

VP Development & COO                    Director, Office of Research Services
-------------------------------         -------------------------------------
Title                                   Title

Date: Sept. 21, 1998                    Date: SEP 18 1998
-------------------------------         -------------------------------------

Agreed and Accepted:    /s/ William Bennett
                        --------------------------
                        Principal Investigator

                        Date: 8/12/98
                        --------------------------
<PAGE>

                                   EXHIBIT A

                       CLINICAL TRIAL PROTOCOL AMENDMENT

                       [CONFIDENTIAL TREATMENT REQUESTED]
<PAGE>

                     AMENDMENT/AGREEMENT TO EXTEND THE TERM
                         OF CLINICAL SERVICES AGREEMENT

        This Amendment is dated effective June 1, 1999 by and between The
University of North Carolina at Chapel Hill (the "University") and Inspire
Pharmaceuticals, Inc. (the "Company"). The University and the Company agree to
amend the Clinical Research Agreement, effective March 10, 1995, as previously
amended (the "Agreement"), as follows:

        1.      Pursuant to Section 8, the term of the Agreement shall be
extended to and including June 30, 2000.

        2.      The name of the person and the address of the Company to whom
notices and other communications to the Company should be directed, as set forth
in Section 17, shall be changed to:

                Christy L. Shaffer, Ph.D.
                President and Chief Executive Officer
                Inspire Pharmaceuticals, Inc.
                4222 Emperor Boulevard, Suite 470
                Durham, North Carolina  27703
                Phone: (919) 941-9777
                Fax:   (919) 941-9797

        3.      Except as expressly provided in this Amendment to the Agreement,
all other terms and conditions of the Agreement shall continue in full force and
effect.

THE UNIVERSITY OF NORTH                        INSPIRE PHARMACEUTICALS, INC.
CAROLINA AT CHAPEL HILL

By /s/ Robert P. Lowman                        By  /s/ Christy L. Shaffer
   ----------------------------                   ----------------------------
   Robert P. Lowman                               Christy L. Shaffer, Ph.D.
   Associate Vice Provost and                     President and CEO
   Director, Office of Research Services

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