Document:

<PAGE>

                                                                  EXHIBIT 10.191

10/15/02

                    SECOND LEASE AMENDMENT TO LEASE AGREEMENT

     THIS SECOND AMENDMENT TO LEASE AGREEMENT (hereinafter referred to as the
"Amendment") is made as of the 1st day of October 2002, by and between DUKE
REALTY LIMITED PARTNERSHIP, an Indiana limited partnership doing business in
North Carolina as Duke Realty of Indiana Limited Partnership, successor by
merger to Weeks Realty, L.P. (hereinafter referred to as "Landlord") and PPD
Development LP,., a Texas limited partnership and successor in interest to PPD
Development, Inc. (hereinafter referred to as "Tenant").

                                   WITNESSETH:

     WHEREAS, pursuant to a Lease Agreement dated June 26, 1998 by and between
Landlord and Tenant (the Lease Agreement, and all amendments thereto shall be
referred to herein collectively as the "Lease"), Landlord leased to Tenant
certain premises containing approximately 72,962 rentable square feet in a
building located on certain land (the "Land") which had been provided the
address of 4023 Paramount Parkway, but is now known as 3900 South Paramount
Parkway, Morrisville, Wake County, North Carolina 27560 (the "Premises"), all as
more particularly described in the Lease; and

     WHEREAS, pursuant to a First Amendment to Lease Agreement dated October 28,
1998, Landlord and Tenant amended the lease, among other things, to confirm the
actual square footage of the Premises and to expand the Premises; and

     WHEREAS, the parties hereto desire to amend the Lease to, among other
things, extend the term of the Lease, provide for the abatement of one month of
Base Rent and to provide a Tenant Improvement Allowance, as provided herein.

     NOW, THEREFORE, for and in consideration of Ten Dollars ($10.00) paid by
Landlord and Tenant to one another, and for other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged by
Landlord and Tenant, Landlord and Tenant amend the Agreement as follows:

     1.  Premises and Term.

     Term. Tenant currently leases 72,962 rentable square feet at the Building.
The Termination Date under the Lease for the Premises, is hereby extended
through and including November 8, 2013 (the "Revised Termination Date").

     2.  Base Rent, Operating Expenses and Security Deposit.

     (a) Base Rent. Paragraph 2 (a) of the Lease is hereby amended by adding the
following new paragraph at the end thereof:

     "Tenant's base rent for the month of January 2003 shall be fully and
     completely abated, provided that Tenant is not in default of the Lease at
     the time the base rent for January 2003 would otherwise be due and owing.
     On November 8, 2008, Tenant's base rent shall be adjusted to the then
     current Market Rent (as defined in the Lease) and taking into account the
     readjustment of the Operating Expenses as set out in paragraph 2(b) below;
     provided, however, that in no event shall the base rent per square foot, as
     adjusted, be less than Tenant's then current rent."

                                        1

<PAGE>

     (b)  Operating Expenses. Effective on November 8, 2008, Article 2(b)(ii) of
the Lease is hereby amended by deleting the following:

          "(ii) the amount of operating expenses (as defined below) for the
     Building to the extent operating expenses exceed the actual amount of
     operating expenses for the first twelve months of occupancy of any portion
     of the Building per rentable square foot of the Building in any lease year
     during the term of this Lease; provided, however, an amount equal to $1.25
     per rentable square foot shall be used as the expense stop for the Tenant
     for utilities for the first lease year of the Lease."

And replacing it with the following:

          "(ii) the amount of operating expenses for the Building to the extent
     operating expenses exceed the actual amount of operating expenses for the
     calendar year 2008 per rentable square foot of the Building in any lease
     year during the extended term of this Lease."

     3.   Tenant Improvements.

     (a)  Landlord shall provide Tenant with a tenant improvement allowance of
Four Hundred Seventy-four Thousand Two Hundred Fifty-Three Dollars ($474,253.00)
(the "Tenant Improvement Allowance"). The Tenant Improvement Allowance shall be
applied toward construction, engineering, professional, telecommunication,
design, project management, plan review, permits, architecture, voice and data
cabling and other costs and expenses associated with the Tenant Improvements (as
hereinafter defined) to the Premises. Landlord shall be responsible for the
payment of all costs and expense associated with improvements to the Premises up
to the Tenant Improvement Allowance, whether such improvements are performed by
Landlord, Duke Construction Limited Partnership, any other subsidiary or
affiliate of Landlord, Tenant or any other person or entity, and Tenant shall
have no responsibility therefor. Any cost or expense incurred by Landlord and
approved by Tenant in connection with the Tenant improvements to the Premises in
excess of the Tenant Improvement Allowance (the "Excess") shall be borne by
Tenant and shall be paid by Tenant to Landlord within thirty (30) days of
Tenant's receipt of an invoice from Landlord providing sufficient detail and
documentation for such costs and expenses. Failure by Tenant to pay any portion
of the Excess as aforesaid is an event of default hereunder.

     (b)  Following the date of this Amendment, Tenant will work with a space
planner to develop a space plan for the Premises that is reasonably acceptable
to Landlord (the "Space Plan"). Within thirty (30) days after Landlord's receipt
of the Space Plan, Tenant shall prepare and submit to Landlord a set of plans
and specifications and/or construction drawings (the "Plans and Specifications")
prepared by an architect reasonably acceptable to Landlord covering all work to
be performed by Landlord in constructing the leasehold improvements to the
Premises in accordance with the Space Plan (the "Tenant Improvements"). Landlord
shall participate in the design meetings with Tenant's architect to maintain
Landlord's building standard and to provide preconstruction cost estimating.
Landlord shall have ten (10) days after receipt of the Plans and Specifications
in which to review the Plans and Specifications and to give Tenant written
notice of Landlord's approval of the Plans and Specifications or its requested
changes to the Plans and Specifications. Tenant shall have no right to request
any leasehold improvements or any changes to the Plans and Specifications that
would materially alter the Premises, the exterior appearance or basic nature of
the Building, or the Building systems. If Landlord fails to approve or request
changes to the Plans and Specifications within ten (10) days after its receipt
of the Plans and Specifications, then Landlord shall be deemed to have approved
the Plans and Specifications and the same shall thereupon be final. If Landlord
requests any changes

                                        2

<PAGE>

to the Plans and Specifications, Tenant shall make those changes which are
reasonably requested by Landlord and shall within ten (10) business days of its
receipt of such request submit the revised portion of the Plans and
Specifications to Landlord. Landlord may not thereafter disapprove the revised
portions of the Plans and Specifications unless Tenant has unreasonably failed
to incorporate reasonable comments of Landlord and, subject to the foregoing,
the Plans and Specifications, as modified by said revisions, shall be deemed to
be final upon the submission of said revisions to Landlord. Landlord shall at
all times in its review of the Plans and Specifications, and of any revisions
thereto, act reasonably and in good faith. Landlord agrees to confirm Landlord's
consent to the Plans and Specifications in writing within three (3) business
days following Tenant's written request therefor.

     (c) Following Landlord's approval (or deemed approval) of the Plans and
Specifications, Landlord shall solicit competitive bids from at least three (3)
subcontractors for each major trade. Landlord shall provide Tenant with
Landlord's form for prequalifying subcontractors, attached hereto as Exhibit A
and incorporated herein, and its current list of approved subcontractors for
each major trade, attached hereto as Exhibit B and incorporated herein. Tenant
shall have the right to provide Landlord with a proposed subcontractor for each
major trade which may or may not be on Landlord's approved list, and provided
such subcontractor meets with Landlord's reasonable approval, such subcontractor
shall have the right to enter a bid. Upon Tenant's request, Landlord shall also
obtain a description of the base warranty and any extended warranty terms
relating to any equipment, machinery, trade fixtures or other personal property
to be installed in connection with the Tenant Improvements. Landlord and Tenant
shall review the bids and warranties, if applicable, jointly and Tenant shall
select one subcontractor for each item bid. Promptly following the selection of
a subcontractor for each major trade, Landlord shall deliver to Tenant a
statement of the cost to construct and install all of the Tenant Improvements
(the "Cost Statement"). Tenant acknowledges and agrees that (i) the cost to
construct and install the Tenant Improvements shall include a six percent (6%)
fee plus (A) Landlord's actual overhead expenses associated with the Tenant
Improvements that includes preconstruction and project management,
administrative support, telephones, utilities, etc., and (B) Landlord's actual
cost of general conditions associated with the Tenant Improvements that include,
but are not limited to, permits, onsite supervision, temporary utilities,
temporary facilities and project cleanup, (such overhead and general conditions
shall not exceed eight percent (8%) of the total construction costs for the
Tenant Improvements), and (ii) said fee, overhead and general conditions shall
be included in the Cost Statement and applied against the Tenant Improvement
Allowance (as hereinafter defined). Tenant agrees to acknowledge the Cost
Statement in writing within five (5) business days following Landlord's written
request therefor.

     (d) Landlord shall provide Tenant with a proposed schedule for the
construction and installation of the Tenant Improvements that is reasonably
acceptable to Tenant and shall perform the construction in accordance with such
schedule and the Plans and Specifications, subject to extensions for Force
Majeure Delays and Tenant Delays (as hereinafter defined). Landlord shall notify
Tenant of any material changes to said schedule as a result of such Force
Majeure Delays and Tenant Delays. In the event the Tenant Improvements are not
Substantially Completed (as hereafter defined) in accordance with the schedule
as extended by Force Majeure Delays and Tenant Delays, Tenant shall receive one
day of rent abatement for each day of delay until the Tenant Improvements are
Substantially Completed. Tenant agrees to coordinate with Landlord regarding the
installation of Tenant's phone and data wiring and any other trade related
fixtures that will need to be installed in the Premises prior to Substantial
Completion. In addition, if and to the extent permitted by applicable laws,
rules and ordinances, Tenant shall have the right to enter the Premises for
fifteen (15) days prior to the anticipated date for Substantial Completion (as
such date may be modified from time to time) in order to install fixtures and
otherwise prepare the Premises for

                                        3

<PAGE>

occupancy. During any entry prior to the Substantial Completion of the Tenant
Improvements (i) Tenant shall not interfere with Landlord's completion of the
Tenant Improvements, and (ii) Tenant shall cause its personnel and contractors
to comply with the terms and conditions of Landlord's rules of conduct (which
Landlord agrees to furnish to Tenant upon request).

     (e) Tenant shall have the right to request changes to the Plans and
Specifications at any time by way of written change order (each, a "Change
Order", and collectively, "Change Orders"). Provided such Change Order is
reasonably acceptable to Landlord, Landlord shall prepare and submit promptly to
Tenant a memorandum setting forth the impact on cost and schedule resulting from
said Change Order (the "Change Order Memorandum of Agreement"). Tenant shall,
within five (5) business days following Tenant's receipt of the Change Order
Memorandum of Agreement, either (i) execute and return the Change Order
Memorandum of Agreement to Landlord, in which case the Cost Statement shall be
deemed modified automatically to take into account said Change Order, (ii)
retract its request for the Change Order or (iii) amend its proposed Change
Order, in which case Landlord shall prepare a new Change Order Memorandum of
Agreement and Tenant shall respond as provided herein.

     (f) For purposes of this Amendment "Substantial Completion" (or any
grammatical variation thereof) shall mean completion of construction of the
Tenant Improvements, subject only to punchlist items to be identified by
Landlord and Tenant in a joint inspection of the Premises prior to Tenant's
occupancy, the completion of which will not materially affect Tenant's use and
occupancy of, or ability to obtain an occupancy permit for the Premises which
completion and punchlist items shall be evidenced by a writing signed by Tenant
and Landlord (Tenant acknowledging, however, that even if Landlord has
Substantially Completed the Tenant Improvements, Landlord may not be able to
obtain an occupancy permit for the Premises because of the need for completion
of all or a portion of improvements being installed in the Premises directly by
Tenant). "Tenant Delay" shall mean any delay in the completion of the Tenant
Improvements to the extent attributable to Tenant, including, without
limitation, (i) Tenant's failure to meet any time deadlines specified herein,
(ii) the performance of any other work in the Premises by any person, firm or
corporation employed by or on behalf of Tenant, or any failure to complete or
delay in completion of such work, and (iii) any other act or omission of Tenant.
"Force Majeure Delay" shall mean any delay in the performance of any obligation
by a party hereunder when such delay is occasioned by causes beyond its control
due to act of God, adverse weather, fire, earthquake, flood, explosion, war,
invasion, insurrection, riot, mob violence, sabotage, vandalism, failure of
transportation, strikes, lockouts, litigation, condemnation, requisition,
governmental restrictions including inability or delay in obtaining governmental
consents, inspections or permits, laws or orders of governmental, civil,
military or naval authorities, or any other cause outside a party's control,
whether similar or dissimilar to the foregoing.

     (g) Landlord hereby warrants the Tenant Improvements for a period of one
(1) year following the date of Substantial Completion. Landlord agrees to assign
any and all manufacturers' warranties or extended warranties, if obtained,
directly to the Tenant, which warranties shall include, but not be limited to,
the standard warranties available from the manufacturers, and if not assignable,
shall cooperate with Tenant to enforce such warranties.

     (h) Notwithstanding anything herein to the contrary, at any time and from
time to time after the date first set forth above and prior to October 1, 2007,
whether or not Tenant has made any improvements to the Premises, Tenant may
request Landlord to pay Tenant all or a portion of the unused Tenant Improvement
Allowance, and Landlord shall disburse such amount to Tenant in cash within
thirty (30) days of

                                        4

<PAGE>

Landlord's receipt of Tenant's request therefore. In addition, all shelves,
bins, machinery and other trade fixtures installed in connection with any Tenant
improvements to the Premises may be removed by Tenant in accordance with the
provisions of Paragraph 5 of the Lease.

     4.  Effective Date. The provisions of this Amendment shall be and become
effective as of the date and year first above written.

     5.  Severability. In the event any term, covenant or condition of this
Amendment, the Lease, or any amendments thereto shall to any extent be invalid
or unenforceable, the remainder shall not be affected thereby and each term,
covenant or condition shall be valid and enforceable to the full extent
permitted by law.

     6.  Successors and Assigns. This Amendment shall apply to, inure to the
benefit of, and be binding upon the parties hereto and upon their respective
heirs, legal representatives, successors and permitted assigns, except as
otherwise provided herein.

     7.  Authority of Tenant. Tenant certifies to Landlord that it is authorized
to enter into this Amendment, and that those persons signing below on its behalf
are authorized to do so, and shall promptly upon the request of Landlord provide
a resolution to this effect.

     8.  Interpretation. Although the printed provisions of this Amendment were
drafted by Landlord, such fact shall not cause this Amendment to be construed
either for or against Landlord or Tenant. All capitalized terms, not otherwise
defined, shall be defined as provided in the Lease.

     9.  Full Force and Effect. Except as modified hereby, the Lease remains
unmodified and in full force and effect.

     10. Governing Law. This Amendment shall be governed by and construed in
accordance with the laws of the State of North Carolina.

     11. Mutual Acknowledgment of Non-Existence of Claims. Landlord and Tenant
acknowledge and agree that as of the day hereof there are no known claims by
either party against the other party hereto arising from the relationship as
Landlord and Tenant, respectively, pursuant to the Lease, as amended.

     12. Confidentiality. Except as otherwise required by law to be disclosed by
Tenant the terms and provisions of the Lease, and this Amendment are strictly
confidential, are to be shared by Tenant only with its accountant, employees,
and attorneys, and each of those parties shall be advised of the confidential
nature of the lease, and this Amendment.

     13. Guaranty. In consideration of this Amendment, Tenant shall provide
Landlord with a Guaranty of Lease executed by Pharmaceutical Product
Development, Inc. in the form attached hereto as Exhibit C.

                                        5

<PAGE>

     IN WITNESS WHEREOF, the undersigned have caused this Amendment to be
executed under seal and delivered as of the day and year first above written.

                                        LANDLORD:

                                        DUKE REALTY LIMITED PARTNERSHIP,
                                        an Indiana limited partnership doing
                                        business in North Carolina as Duke
                                        Realty of Indiana Limited Partnership

                                             By:  Duke Realty Corporation,
                                                  an Indiana corporation, its
                                                  General Partner

                                             By:  /s/ H. Andrew Kelton
                                                -------------------------------
                                             Name:  H. Andrew Kelton
                                                  -----------------------------
                                             Title:  Senior V. P.
                                                   ----------------------------

ATTEST:                                 TENANT:

   By:  /s/ B. Judd Hartman             PPD Development, LP., a Texas limited
       ---------------------------
   Name: B. Judd Hartman                partnership
         -------------------------
   Title:  Secretary                    By:  PPD GP LLC, a Delaware limited
         -------------------------
                                        liability company, its General Partner

                                             By:  /s/ Fred B. Davenport, Jr.
                                                -------------------------------
                                             Name:  Fred B. Davenport, Jr.
                                                  -----------------------------
                                             Title:  Vice President
                                                   ----------------------------

                                        6

<PAGE>

                                    EXHIBIT A

                      FORM FOR PREQUALIFYING SUBCONTRACTORS

<PAGE>

                                    EXHIBIT B

                           LANDLORD'S CURRENT LIST OF
                             APPROVED SUBCONTRACTORS

<PAGE>

                                    EXHIBIT C

                                GUARANTY OF LEASE

STATE OF NORTH CAROLINA                 :
COUNTY OF WAKE                          :    GUARANTY OF LEASE

     THIS GUARANTY OF LEASE (the "Guaranty"), is made and entered into as of the
1st day of October, 2002, by and between PHARMACEUTICAL PRODUCT DEVELOPMENT,
INC., a North Carolina corporation (hereinafter the "Guarantor") to DUKE REALTY
LIMITED PARTNERSHIP, an Indiana limited partnership doing business in North
Carolina as Duke Realty of Indiana Limited Partnership (the "Landlord");

                              W I T N E S S E T H:

     WHEREAS, pursuant to a Lease Agreement, dated June 26, 1998 by and between
Landlord and Tenant (the Lease Agreement, and all amendments thereto shall be
referred to herein collectively as the "Lease"), Landlord leased to Tenant
certain premises containing approximately 72,962 rentable square feet in a
building located on certain land (the "Land") which had been provided the
address of 4023 Paramount Parkway, but in now known as 3900 South Paramount
Parkway, Morrisville, Wake County, North Carolina 27560 (the "Premises"), all as
more particularly described in the Lease; and

     WHEREAS, the Lease is incorporated herein by this reference; and

     WHEREAS, Guarantor has a monetary interest in Tenant and in the Lease and
shall benefit from the execution of the Lease, and is willing to enter into this
Guaranty;

     NOW, THEREFORE, for and in consideration of the Lease, and as an inducement
to Landlord to enter into the same, the Guarantor for itself and its heirs,
successors and assigns, guarantees the full and punctual payment of all base
rent, additional rent, and any and all other sums payable to Tenant to Landlord
under the Lease, when and as the same shall be due and payable under the terms
of the Lease, and guarantees to Landlord the due and punctual performance by
Tenant of each and every term, covenant and condition contained in the Lease to
be observed or performed by the Tenant thereunder; and in the event Tenant shall
default in the payment or performance of the Lease, Guarantor hereby agrees
immediately upon Landlord's request to pay the sums due Landlord or to perform
the defaulted or breached term, covenant or condition of the Lease and to pay
all expenses and costs (including, but not limited to, legal costs and
reasonable attorneys' fees) paid or incurred by Landlord in enforcing the
obligations of the Guarantor under this Guaranty.

     Guarantor hereby consents and agrees that Landlord at any time, and from
time to time, without notice to or further consent from Guarantor, and without
releasing, discharging, modifying or otherwise affecting the obligations and
liabilities of Guarantor in any manner, either with or without consideration,
may upon notice to Guarantor, grant releases, compromises, waivers of compliance
and other indulgences with respect to the Lease and this Guaranty to any persons
or entities now or hereafter liable thereunder or hereunder, release any
Guarantor or any other obligor under the Lease or this Guaranty, all without
affecting the obligations and liabilities of Guarantor hereunder.

     The obligations of Guarantor under this Guaranty shall be direct and
immediate and not conditional or contingent upon the pursuit of any rights or
remedies against Tenant or any other person, not against securities or lien
rights available to Landlord. Guarantor waives any right to require that an
action be brought against Tenant or any other person or entity or to require
that resort be had to any security prior to demand on Guarantor hereunder being
made or prior to enforcement of the Guaranty. In the event of default under the
Lease, Landlord shall have the right to enforce its rights, powers and remedies
thereunder or hereunder in any other, or not at all, and all powers and remedies
available to Landlord in such event shall be nonexclusive and cumulative of all
other rights, powers and remedies provided under the Lease or hereunder or by
law, in equity, or contract.

     Guarantor waives any and all rights to require that Landlord pursue any
other remedy or any other right prior to its pursuit under this Guaranty, and
Guarantor hereby waives the provisions of Chapter 26 of the North Carolina
General Statutes, including, but not limited to, the provisions of N.C. Gen.
Stat. Sec. 26-7, as amended.

     This Guaranty shall be governed by, and be construed in accordance with,
the laws of the State of North Carolina.

<PAGE>

     This Guaranty may not be changed orally or by implication, and no
obligation of the Guarantor or anyone or more of them can be released or waived
by Landlord or any officer, agent, or employee of Landlord, except by writing
signed by a duly authorized partner or agent of Landlord. This Guaranty shall be
irrevocable by Guarantor until all amounts guaranteed hereby have been
completely paid and all terms, covenants and conditions of the Lease guaranteed
hereby have been performed and all obligations and undertakings of Guarantor
hereunder have been completely performed.

     Any notice or demand which by any provision of this Guaranty is required or
allowed to be given to any Guarantor shall be deemed to have been sufficiently
given for all purposes when made in writing and either delivered personally or
delivered to an overnight courier service or deposited in the United States mail
as certified or registered mail, postage prepaid, and either addressed to the
Guarantor concerned at the address appearing beside its signature below or to
such other address as any Guarantor shall furnish to Landlord in writing, the
receipt of which shall be acknowledged in writing by Landlord.

     The provisions of this Guaranty shall be binding upon Guarantor and its
heirs, successors, legal representatives, and assigns. This Guaranty shall in no
event be impaired by any change which may arise by reason of the bankruptcy or
dissolution of Tenant.

     IN WITNESS WHEREOF, the undersigned have executed this Guaranty under seal
as of the day and year first set forth above.

WITNESS:                             GUARANTOR:

                                     PHARMACEUTICAL PRODUCT
                                     DEVELOPMENT, INC., a North Carolina
                                     corporation

 /s/ B. Judd Hartman                 By: /s/ Fred B. Davenport, Jr.
-------------------------------         -------------------------------------
Print Name: B. Judd Hartman          Print Name: Fred B. Davenport, Jr.,
           --------------------                 -----------------------------
                                                 President
                                                -----------------------------
                                     Address:    3151 South 17/th/ Street
                                             --------------------------------
                                                 Wilmington, NC 28412
                                     ----------------------------------------
                                     FEIN:  56 1640186
                                           -----------------------------<PAGE>

                                                                  EXHIBIT 10.192

10/15/02

                    FIFTH LEASE AMENDMENT TO LEASE AGREEMENT

     THIS FIFTH AMENDMENT TO LEASE AGREEMENT (hereinafter referred to as the
"Amendment") is made as of the 1st day of October 2002, by and between DUKE
REALTY LIMITED PARTNERSHIP, an Indiana limited partnership doing business in
North Carolina as Duke Realty of Indiana Limited Partnership, successor by
merger to Weeks Realty, L.P. (hereinafter referred to as "Landlord") and PPD
Development, LP, a Texas limited partnership and successor in interest to PPD
Development, Inc. (hereinafter referred to as "Tenant").

                                   WITNESSETH:

     WHEREAS, pursuant to a Lease Agreement dated July 9, 1997 by and between
Landlord and Tenant (the Lease Agreement, and all amendments thereto shall be
referred to herein collectively as the "Lease"), Landlord leased to Tenant
certain premises containing approximately 100,987 rentable square feet in a
building located on certain land (the "Land") at 3900 North Paramount Parkway,
Morrisville, Wake County, North Carolina 27560 (the "Premises"), all as more
particularly described in the Lease; and

     WHEREAS, pursuant to a First Amendment to Lease Agreement dated January 28,
1998, Landlord and Tenant amended the lease, among other things, to correct and
modify the square footage leased by Tenant in the Building, as provided therein;
and

     WHEREAS, pursuant to a Second Amendment to Lease Agreement dated as of June
26, 1998, Landlord and Tenant amended the Lease, among other things, to modify
the Lease to revise the provisions of paragraph 9 of the Lease, as provided
therein, and

     WHEREAS, pursuant to a Third Amendment to Lease Agreement dated as of
February 18, 1999, Landlord and Tenant amended the Lease, among other things, to
modify its provisions regarding the termination of certain lease agreements
between Landlord and Tenant, as provided therein;

     WHEREAS, pursuant to a Fourth Amendment to Lease Agreement dated as of July
6, 1999, Landlord and Tenant amended the Lease, among other things, to modify
the Lease to revise the provisions of paragraph 2(a) of the Lease, as provided
therein, and

     WHEREAS, the parties hereto desire to amend the Lease, among other things,
to extend the term of the Lease, provide for the abatement of one month of Base
Rent and to provide a Tenant Improvement Allowance, as provided herein.

     NOW, THEREFORE, for and in consideration of Ten Dollars ($10.00) paid by
Landlord and Tenant to one another, and for other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged by
Landlord and Tenant, Landlord and Tenant amend the Agreement as follows:

     1. Premises and Term

     Term. Tenant currently leases 100,987 rentable square feet at the Building.
The Termination Date under the Lease for the Premises, is hereby extended
through and including November 8, 2013 (the "Revised Termination Date").

<PAGE>

     2.  Base Rent, Operating Expenses and Security Deposit.

     (a) Base Rent. Paragraph 2 (a) of the Lease is hereby amended by adding the
following new paragraph at the end thereof:

     "Tenant's base rent, including operating expenses, but not Additional Rent,
for the month of January 2003 shall be fully and completely abated, provided
that Tenant is not in default of the Lease at the time the base rent for January
2003 would otherwise be due and owing. On November 8, 2008, Tenant's base rent
shall be adjusted to the then current Market Rent (as defined in the Lease) and
taking into account the readjustment of the operating expenses as set out in
paragraph 2(b) below; provided, however, that in no event shall the base rent
per square foot, as adjusted, be less than Tenant's then current rent."

     (b) Operating Expenses. Effective on November 8, 2008, Article 2(b)(ii) of
the Lease is hereby amended by deleting the following:

         (ii)  the amount of operating expenses (as defined below) for the
     Building to the extent operating expenses exceed the actual amount of
     operating expenses for the first twelve months of occupancy of any portion
     of the Building per rentable square foot of the Building in any lease year
     during the term of this Lease; provided, however, an amount equal to $1.25
     per rentable square foot shall be used as the expense stop for the Tenant
     for utilities for the first lease year of the Lease."

And replacing it with the following:

         "(ii) the amount of operating expenses (as defined below) for the
     Building to the extent operating expenses exceed the actual amount of
     operating expenses for the calendar year 2008 per rentable square foot of
     the Building in any lease year during the extended term of this Lease."

     3.  Additional Space. Paragraph 1(d) of the Lease is deleted in its
entirety and is of no further force or effect.

     4.  Tenant Improvements.

     (a) Landlord shall provide Tenant with a tenant improvement allowance of
Six Hundred Fifty-Six Thousand Four Hundred Fifteen Dollars ($656,415.00) (the
"Tenant Improvement Allowance"). The Tenant Improvement Allowance shall be
applied toward construction, engineering, professional, telecommunication,
design, project management, plan review, permits, architecture, voice and data
cabling and other costs and expenses associated with the Tenant Improvements (as
hereinafter defined) to the Premises. Landlord shall be responsible for the
payment of all costs and expense associated with improvements to the Premises up
to the Tenant Improvement Allowance, whether such improvements are performed by
Landlord, Duke Construction Limited Partnership, any other subsidiary or
affiliate of Landlord. Any cost or expense incurred by Landlord and approved by
Tenant in connection with the Tenant improvements to the Premises in excess of
the Tenant Improvement Allowance (the "Excess") shall be borne by Tenant and
shall be paid by Tenant to Landlord within thirty (30) days of Tenant's receipt
of an invoice from Landlord providing sufficient detail and documentation for
such costs and expenses. Failure by Tenant to pay any portion of the Excess as
aforesaid is an event of default hereunder.

     (b) Following the date of this Amendment, Tenant will work with a space
planner to develop a space plan for the Premises that is reasonably acceptable
to Landlord (the "Space Plan"). Within thirty (30) days after Landlord's receipt
of the

<PAGE>

Space Plan, Tenant shall prepare and submit to Landlord a set of plans and
specifications and/or construction drawings (the "Plans and Specifications")
prepared by an architect reasonably acceptable to Landlord covering all work to
be performed by Landlord in constructing the leasehold improvements to the
Premises in accordance with the Space Plan (the "Tenant Improvements"). Landlord
shall participate in the design meetings with Tenant's architect to maintain
Landlord's building standards and to provide preconstruction cost estimating.
Landlord shall have ten (10) days after receipt of the Plans and Specifications
in which to review the Plans and Specifications and to give Tenant written
notice of Landlord's approval of the Plans and Specifications or its requested
changes to the Plans and Specifications. Tenant shall have no right to request
any leasehold improvements or any changes to the Plans and Specifications that
would materially alter the Premises, the exterior appearance or basic nature of
the Building, or the Building systems. If Landlord fails to approve or request
changes to the Plans and Specifications within ten (10) days after its receipt
of the Plans and Specifications, then Landlord shall be deemed to have approved
the Plans and Specifications and the same shall thereupon be final. If Landlord
requests any changes to the Plans and Specifications, Tenant shall make those
changes which are reasonably requested by Landlord and shall within ten (10)
business days of its receipt of such request submit the revised portion of the
Plans and Specifications to Landlord. Landlord may not thereafter disapprove the
revised portions of the Plans and Specifications unless Tenant has unreasonably
failed to incorporate reasonable comments of Landlord and, subject to the
foregoing, the Plans and Specifications, as modified by said revisions, shall be
deemed to be final upon the submission of said revisions to Landlord. Landlord
shall at all times in its review of the Plans and Specifications, and of any
revisions thereto, act reasonably and in good faith. Landlord agrees to confirm
Landlord's consent to the Plans and Specifications in writing within three (3)
business days following Tenant's written request therefor.

     (c) Following Landlord's approval (or deemed approval) of the Plans and
Specifications, Landlord shall solicit competitive bids from at least three (3)
subcontractors for each major trade. Landlord shall provide Tenant with
Landlord's form for prequalifying subcontractors, attached hereto as Exhibit A
and incorporated herein, and its current list of approved subcontractors for
each major trade, attached hereto as Exhibit B and incorporated herein. Tenant
shall have the right to provide Landlord with a proposed subcontractor for each
major trade which may or may not be on Landlord's approved list, and provided
such subcontractor meets with Landlord's reasonable approval, such subcontractor
shall have the right to enter a bid. Upon Tenant's request, Landlord shall also
obtain a description of the base warranty and any extended warranty terms
relating to any equipment, machinery, trade fixtures or other personal property
to be installed in connection with the Tenant Improvements. Landlord and Tenant
shall review the bids and warranties, if applicable, jointly and Tenant shall
select one subcontractor for each item bid. Promptly following the selection of
a subcontractor for each major trade, Landlord shall deliver to Tenant a
statement of the cost to construct and install all of the Tenant Improvements
(the "Cost Statement"). Tenant acknowledges and agrees that (i) the cost to
construct and install the Tenant Improvements shall include a six percent (6%)
fee plus (A) Landlord's actual overhead expenses associated with the Tenant
Improvements that includes preconstruction and project management,
administrative support, telephones, utilities, etc., and (B) Landlord's actual
costs of general conditions associated with the Tenant Improvements that
include, but are not limited to, permits, onsite supervision, temporary
utilities, temporary facilities and project cleanup, (such overhead and general
conditions shall not exceed eight percent (8%) of the total construction costs
for the Tenant Improvements), and (ii) said fee, overhead and general conditions
shall be included in the Cost Statement and applied against the Tenant
Improvement Allowance (as hereinafter defined). Tenant agrees to acknowledge the
Cost Statement in writing within five (5) business days following Landlord's
written request therefor.

<PAGE>

     (d) Landlord shall provide Tenant with a proposed schedule for the
construction and installation of the Tenant Improvements that is reasonably
acceptable to Tenant and shall perform the construction in accordance with such
schedule and the Plans and Specifications, subject to extensions for Force
Majeure Delays and Tenant Delays (as hereinafter defined). Landlord shall notify
Tenant of any material changes to said schedule as a result of such Force
Majeure Delays and Tenant Delays. In the event the Tenant Improvements are not
Substantially Completed (as hereafter defined) in accordance with the schedule
as extended by Force Majeure Delays and Tenant Delays, Tenant shall receive one
day of rent abatement for each day of delay until the Tenant Improvements are
Substantially Completed. Tenant agrees to coordinate with Landlord regarding the
installation of Tenant's phone and data wiring and any other trade related
fixtures that will need to be installed in the Premises prior to Substantial
Completion. In addition, if and to the extent permitted by applicable laws,
rules and ordinances, Tenant shall have the right to enter the Premises for
fifteen (15) days prior to the anticipated date for Substantial Completion (as
such date may be modified from time to time) in order to install fixtures and
otherwise prepare the Premises for occupancy. During any entry prior to the
Substantial Completion of the Tenant Improvements (i) Tenant shall not interfere
with Landlord's completion of the Tenant Improvements, and (ii) Tenant shall
cause its personnel and contractors to comply with the terms and conditions of
Landlord's rules of conduct (which Landlord agrees to furnish to Tenant upon
request).

     (e) Tenant shall have the right to request changes to the Plans and
Specifications at any time by way of written change order (each, a "Change
Order", and collectively, "Change Orders"). Provided such Change Order is
reasonably acceptable to Landlord, Landlord shall prepare and submit promptly to
Tenant a memorandum setting forth the impact on cost and schedule resulting from
said Change Order (the "Change Order Memorandum of Agreement"). Tenant shall,
within five (5) business days following Tenant's receipt of the Change Order
Memorandum of Agreement, either (i) execute and return the Change Order
Memorandum of Agreement to Landlord, in which case the Cost Statement shall be
deemed modified automatically to take into account said Change Order, (ii)
retract its request for the Change Order, or (iii) amend its proposed Change
Order, in which case Landlord shall prepare a new Change Order Memorandum of
Agreement and Tenant shall respond as provided herein.

     (f) For purposes of this Amendment "Substantial Completion" (or any
grammatical variation thereof) shall mean completion of construction of the
Tenant Improvements, subject only to punchlist items to be identified by
Landlord and Tenant in a joint inspection of the Premises prior to Tenant's
occupancy, the completion of which will not materially affect Tenant's use and
occupancy of, or ability to obtain an occupancy permit for the Premises which
completion and punchlist items shall be evidenced by a writing signed by Tenant
and Landlord (Tenant acknowledging, however, that even if Landlord has
Substantially Completed the Tenant Improvements, Landlord may not be able to
obtain an occupancy permit for the Premises because of the need for completion
of all or a portion of improvements being installed in the Premises directly by
Tenant). "Tenant Delay" shall mean any delay in the completion of the Tenant
Improvements to the extent attributable to Tenant, including, without
limitation, (i) Tenant's failure to meet any time deadlines specified herein,
(ii) the performance of any other work in the Premises by any person, firm or
corporation employed by or on behalf of Tenant, or any failure to complete or
delay in completion of such work, and (iii) any other act or omission of Tenant.
"Force Majeure Delay" shall mean any delay in the performance of any obligation
by a party hereunder when such delay is occasioned by causes beyond its control
due to act of God, adverse weather, fire, earthquake, flood, explosion, war,
invasion, insurrection, riot, mob violence, sabotage, vandalism, failure of
transportation, strikes, lockouts, litigation, condemnation, requisition,
governmental restrictions including inability or delay in obtaining governmental
consents,

<PAGE>

inspections or permits, laws or orders of governmental, civil, military or naval
authorities, or any other cause outside the party's control, whether similar or
dissimilar to the foregoing.

     (g) Landlord hereby warrants the Tenant Improvements for a period of one
(1) year following the date of Substantial Completion. Landlord agrees to assign
any and all manufacturers' warranties or extended warranties, if obtained,
directly to the Tenant, which warranties shall include, but not be limited to,
the standard warranties available from the manufacturers, and if not assignable,
shall cooperate with Tenant to enforce such warranties.

     (h) Notwithstanding anything herein to the contrary, at any time and from
time to time after the date first set forth above and prior to October 1, 2007,
Tenant may request Landlord to pay Tenant all or a portion of the unused Tenant
Improvement Allowance, and Landlord shall disburse such amount to Tenant in cash
within thirty (30) days of Landlord's receipt of Tenant's request therefor. In
addition, all shelves, bins, machinery and other trade fixtures installed in
connection with any Tenant improvements to the Premises may be removed by Tenant
in accordance with the provisions of Paragraph 5 of the Lease.

     5.  Effective Date. The provisions of this Amendment shall be and become
effective as of the date and year first above written.

     6.  Severability. In the event any term, covenant or condition of this
Amendment, the Lease, or any amendments thereto shall to any extent be invalid
or unenforceable, the remainder shall not be affected thereby and each term,
covenant or condition shall be valid and enforceable to the full extent
permitted by law.

     7.  Successors and Assigns. This Amendment shall apply to, inure to the
benefit of, and be binding upon the parties hereto and upon their respective
heirs, legal representatives, successors and permitted assigns, except as
otherwise provided herein.

     8.  Authority of Tenant. Tenant certifies to Landlord that it is authorized
to enter into this Amendment, and that those persons signing below on its behalf
are authorized to do so, and shall promptly upon the request of Landlord provide
a resolution to this effect.

     9.  Interpretation. Although the printed provisions of this Amendment were
drafted by Landlord, such fact shall not cause this Amendment to be construed
either for or against Landlord or Tenant. All capitalized terms, not otherwise
defined, shall be defined as provided in the Lease.

     10. Full Force and Effect. Except as modified hereby, the Lease remains
unmodified and in full force and effect.

     11. Governing Law. This Amendment shall be governed by and construed in
accordance with the laws of the State of North Carolina.

     12. Mutual Acknowledgment of Non-Existence of Claims. Landlord and Tenant
acknowledge and agree that as of the day hereof there are no known claims by
either party against the other party hereto arising from the relationship as
Landlord and Tenant, respectively, pursuant to the Lease, as amended.

     13. Confidentiality. Except as otherwise required by law to be disclosed by
Tenant, the terms and provisions of the Lease, and this Amendment are strictly
confidential, are to be shared by Tenant only with its accountant, employees,
and

<PAGE>

attorneys, and each of those parties shall be advised of the confidential nature
of the lease, and this Amendment.

     14. Guaranty. In consideration of this Amendment, Tenant shall provide
Landlord with a Guaranty of Lease executed by Pharmaceutical Product
Development, Inc. in the form attached hereto as Exhibit C. ---------

     IN WITNESS WHEREOF, the undersigned have caused this Amendment to be
executed under seal and delivered as of the day and year first above written.

                                     LANDLORD:
                                     DUKE REALTY LIMITED PARTNERSHIP,
                                     an Indiana limited partnership doing
                                     business in North Carolina as Duke
                                     Realty of Indiana Limited Partnership

                                         By: Duke Realty Corporation,
                                             an Indiana corporation, its
                                             General Partner

                                         By: /s/ H. Andrew Kelton
                                            ----------------------------------
                                         Name: H. Andrew Kelton
                                              --------------------------------
                                         Title: Senior V. P.
                                               -------------------------------

ATTEST:                              TENANT:
                                     PPD Development, LP ., a Texas limited
   By: /s/ B. Judd Hartman           partnership
      ------------------------
   Name:  B. Judd Hartman
        ----------------------
   Title: Secretary                      By: PPD GP, LLC, a Delaware
         ---------------------
                                         Limited liability company,
                                         Its General Partner

                                         By: /s/ Fred B. Davenport, Jr.
                                            ----------------------------------
                                         Name: Fred B. Davenport, Jr.
                                              --------------------------------
                                         Title: Vice President
                                               -------------------------------

<PAGE>

                                   EXHIBIT A

                      FORM FOR PREQUALIFYING SUBCONTRACTORS

<PAGE>

                                    EXHIBIT B

                           LANDLORD'S CURRENT LIST OF
                             APPROVED SUBCONTRACTORS

<PAGE>

                                    EXHIBIT C
                                GUARANTY OF LEASE

STATE OF NORTH CAROLINA                    :
COUNTY OF WAKE                             :        GUARANTY OF LEASE

     THIS GUARANTY OF LEASE (the "Guaranty"), is made and entered into as of the
1st day of October, 2002, by and between PHARMACEUTICAL PRODUCT DEVELOPMENT,
INC., a North Carolina corporation (hereinafter the "Guarantor") to DUKE REALTY
LIMITED PARTNERSHIP, an Indiana limited partnership doing business in North
Carolina as Duke Realty of Indiana Limited Partnership (the "Landlord");

                              W I T N E S S E T H:

     WHEREAS, pursuant to a Lease Agreement dated July 9, 1997 by and between
Landlord and Tenant (the Lease Agreement, and all amendments thereto shall be
referred to herein collectively as the "Lease"), Landlord leased to Tenant
certain premises containing approximately 100,987 rentable square feet in a
building located on certain land (the "Land") at 3900 North Paramount Parkway,
Morrisville, Wake County, North Carolina 27560 (the "Premises"), all as more
particularly described in the Lease; and

     WHEREAS, the Lease is incorporated herein by this reference; and

     WHEREAS, Guarantor has a monetary interest in Tenant and in the Lease and
shall benefit from the execution of the Lease, and is willing to enter into this
Guaranty;

     NOW, THEREFORE, for and in consideration of the Lease, and as an inducement
to Landlord to enter into the same, the Guarantor for itself and its heirs,
successors and assigns, guarantees the full and punctual payment of all base
rent, additional rent, and any and all other sums payable to Tenant to Landlord
under the Lease, when and as the same shall be due and payable under the terms
of the Lease, and guarantees to Landlord the due and punctual performance by
Tenant of each and every term, covenant and condition contained in the Lease to
be observed or performed by the Tenant thereunder; and in the event Tenant shall
default in the payment or performance of the Lease, Guarantor hereby agrees
immediately upon Landlord's request to pay the sums due Landlord or to perform
the defaulted or breached term, covenant or condition of the Lease and to pay
all expenses and costs (including, but not limited to, legal costs and
reasonable attorneys' fees) paid or incurred by Landlord in enforcing the
obligations of the Guarantor under this Guaranty.

     Guarantor hereby consents and agrees that Landlord at any time, and from
time to time, without notice to or further consent from Guarantor, and without
releasing, discharging, modifying or otherwise affecting the obligations and
liabilities of Guarantor in any manner, either with or without consideration,
may upon notice to Guarantor, grant releases, compromises, waivers of compliance
and other indulgences with respect to the Lease and this Guaranty to any persons
or entities now or hereafter liable thereunder or hereunder, release any
Guarantor or any other obligor under the Lease or this Guaranty, all without
affecting the obligations and liabilities of Guarantor hereunder.

     The obligations of Guarantor under this Guaranty shall be direct and
immediate and not conditional or contingent upon the pursuit of any rights or
remedies against Tenant or any other person, not against securities or lien
rights available to Landlord. Guarantor waives any right to require that an
action be brought against Tenant or any other person or entity or to require
that resort be had to any security prior to demand on Guarantor hereunder being
made or prior to enforcement of the Guaranty. In the event of default under the
Lease, Landlord shall have the right to enforce its rights, powers and remedies
thereunder or hereunder in any other, or not at all, and all powers and remedies
available to Landlord in such event shall be nonexclusive and cumulative of all
other rights, powers and remedies provided under the Lease or hereunder or by
law, in equity, or contract.

     Guarantor waives any and all rights to require that Landlord pursue any
other remedy or any other right prior to its pursuit under this Guaranty, and
Guarantor hereby waives the provisions of Chapter 26 of the North Carolina
General Statutes, including, but not limited to, the provisions of N.C. Gen.
Stat. Sec. 26-7, as amended.

     This Guaranty shall be governed by, and be construed in accordance with,
the laws of the State of North Carolina.

<PAGE>

     This Guaranty may not be changed orally or by implication, and no
obligation of the Guarantor or anyone or more of them can be released or waived
by Landlord or any officer, agent, or employee of Landlord, except by writing
signed by a duly authorized partner or agent of Landlord. This Guaranty shall be
irrevocable by Guarantor until all amounts guaranteed hereby have been
completely paid and all terms, covenants and conditions of the Lease guaranteed
hereby have been performed and all obligations and undertakings of Guarantor
hereunder have been completely performed.

     Any notice or demand which by any provision of this Guaranty is required or
allowed to be given to any Guarantor shall be deemed to have been sufficiently
given for all purposes when made in writing and either delivered personally or
delivered to an overnight courier service or deposited in the United States mail
as certified or registered mail, postage prepaid, and either addressed to the
Guarantor concerned at the address appearing beside its signature below or to
such other address as any Guarantor shall furnish to Landlord in writing, the
receipt of which shall be acknowledged in writing by Landlord.

     The provisions of this Guaranty shall be binding upon Guarantor and its
heirs, successors, legal representatives, and assigns. This Guaranty shall in no
event be impaired by any change which may arise by reason of the bankruptcy or
dissolution of Tenant.

     IN WITNESS WHEREOF, the undersigned have executed this Guaranty under seal
as of the day and year first set forth above.

WITNESS:                                GUARANTOR:

                                        PHARMACEUTICAL PRODUCT
                                        DEVELOPMENT, INC., a North Carolina
                                        corporation

 /s/ B. Judd Hartman                    By:  /s/ Fred B. Davenport, Jr.
-------------------------------            -------------------------------------
Print Name: B. Judd Hartman             Print Name: Fred B. Davenport, Jr.,
           --------------------                    -----------------------------
                                                    President
                                                   -----------------------------
                                        Address:    3151 South 17/th/ Street
                                                --------------------------------
                                                    Wilmington, NC 28412
                                        ----------------------------------------
                                        FEIN: 56 1640186
                                             -----------------------------------

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00044-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00044-of-00352.parquet"}]]