Exhibit
10.59


PROJECT ADDENDUM


This agreement (“Project
Addendum”) made this 31 day of January, 2005 (the “Effective Date”) by
and between Reliant Pharmaceuticals, Inc., with its principal executive offices
located at 110 Allen Road, Liberty Corner, New Jersey (“Reliant” or “Client”), and PPD Development, LP, successor in interest
to PPD Development, LLC, with its principal executive offices located at
3151 17th Street Extension, Wilmington, North Carolina 28412 (“PPD”).


WHEREAS, a Master Services
Agreement (“Agreement”) by and between PPD and Reliant was executed on December
11, 2001; and


WHEREAS, pursuant to Section 1 of
the Agreement the parties now enter into
this Project Addendum for the purposes of setting forth the responsibilities and obligations of the parties in regard to
conducting certain design, implementation
and analysis services to support the Reliant AFFECTS Program (the
“Services”) which is incorporated herein by reference.


NOW, THEREFORE, for good and
valuable consideration contained herein,
the exchange, receipt and sufficiency of which are acknowledged, the parties
agree as follows:


1.         Services.


PPD shall perform the Services as
outlined in Exhibit A attached to this Project
Addendum.


2.         Compensation and
Payment.


2.1 - Compensation - For its performance under this
Project Addendum, PPD shall receive
compensation as set forth in Exhibit A attached hereto


2.2 - Payment - Payment for the fixed direct costs
shall be made within thirty (30) days of receipt of an invoice.


 


1

















 


2.3 – Payments to PPD shall be made to:


PPD Development, LP

P.O. Box 75468 

Charlotte, NC 28275-5468 

Tax ID# 22-2734293


3.         Term and Termination.


The term of this Project Addendum shall commence on
the Effective Date and end upon the
completion of Services unless otherwise terminated in accordance with
the Agreement.


4.        Incorporation by
Reference/Conflict of Terms.


The terms and conditions of this
Project Addendum and Exhibits hereto are
hereby incorporated into and made a part of the Agreement. To the extent any terms contained in an Exhibit hereto conflict
with this Project Addendum, the terms of this Project Addendum shall control.
In the event of any inconsistency between
the Agreement, the Project Addendum and the Protocol, the terms of the
Protocol shall govern first, followed by the Project Addendum and then by the Agreement unless otherwise specified.


5.         Modifications.


Any changes to this Project Addendum or its Exhibits
shall be documented by written Amendments
upon approval by both parties and shall be attached hereto.


6.        Notices.


Each Party represents that its
respective contact person set forth below shall have the authority to make all
executive decisions regarding this contract. Any notice required or permitted to be given hereunder by either party
hereunder shall be in writing and
shall be deemed given on the date received if delivered personally or by fax or five (5) days after the
date postmarked if sent by registered
or certified U.S. mail, return receipt requested, postage prepaid to the following
address:


 


	
  If to PPD:

  	
  PPD Development, LP

  
	
   

  	
  3151 17th Street
  Extension 

  
	
   

  	
  Wilmington, North
  Carolina 28412 

  
	
   

  	
  Attention: CEO 

  
	
   

  	
  Tel: (910) 251-0081

  
	
   

  	
  Fax: (910)762-5820

  



 


 


2

















	
  If to Reliant:

  	
  Reliant Pharmaceutical,
  Inc.

  
	
   

  	
  110 Allen Road,

  
	
   

  	
  Liberty Corner, New
  Jersey 07938 

  
	
   

  	
  Attention: Chief
  Executive Officer 

  
	
   

  	
  Tel: (908) 542-4485 

  
	
   

  	
  Fax: (908) 542-9406

  



7.        Protocol
Writing


Notwithstanding anything herein
to the contrary, the parties hereby agree and acknowledge that Reliant shall be solely responsible for review,
approval and adoption of the Protocol.


 




	
  PPD
  Development, LP

  	
   

  	
   

  
	
  

  By: 

  	
  

  PPD GP, LLC  

  Its General Partner

  	
   

  	
  By: 

  	
  

  Reliant Pharmaceuticals, Inc.

  
	
  

  By:

  	
  

  /s/ Paul S. Covington

  	
   

  	
  

  By:

  	
  

  /s/ Keith S. Rotenberg

  
	
  

  Name: 

  	
  Paul S. Covington, MD

  	
   

  	
  

  Name: 

  	
  Keith S. Rotenberg, Ph.D.

  
	
  Title:

  	
  Executive Vice President of Development

  	
   

  	
  Title:

  



  	
  Senior Vice President, Research and Development

  Reliant
  Pharmaceuticals, Inc.

  
	
  

  Date:

  	
  21 Feb, 2005

  	
   

  	
  Date:

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  [SEAL]

  






 


3

















	
  [GRAPHIC]

  	
  EXHIBIT A

  	
   

  



Proposal


Design, Implementation
and Analysis Services to Support the

Reliant AFFECTS Program

Atrial Fibrillation: Focus
on Effective Clinical Treatment
Strategies


PRESENTED TO


Keith S. Rotenberg, PhD

Senior Vice President, Research and Development

Reliant Pharmaceuticals

110 Allen Road 

Liberty Corner, NJ 07938

krotenberg@reliantrx.com


PREPARED BY


PPD

Morrisville, NC


DATE


10 September 2004

Revision
#1 – 6 October 2004

Revision #2 – 11
October 2004

Revision #3 – 10
January 2005

Revision #4 – 23
January 2005


 


4

















 


Introduction


 


PPD respectfully submits the following revised proposal to Reliant
Pharmaceuticals (Reliant) to assist with the design and implementation of the
Atrial Fibrillation: Focus on Effective Clinical Treatment Strategies (AFFECTS)
Program, a physician education program and observational registry in atrial
fibrillation.


PPD is a leading global provider of discovery and developmental
services to the pharmaceutical and biotechnology industries, with expertise in
drug development, product launch and marketing support. PPD’s comprehensive
market development service offerings include full service clinical trial
management, registry design and management, medical information support, global
pharmacovigilance support, compliance and persistency programs, medical writing
support, crisis management support, direct-to-consumer program support, risk
management programs and other services. PPD also offers a full suite of
services for products in Phase III or earlier.


PPD has prepared the following revised proposal and cost estimate based
upon discussions with Reliant and its physician advisors regarding the challenges
associated with the proper management of atrial fibrillation patients that do
not have clinically significant structural heart disease or atrial fibrillation
with hypertension but neither LVH (as defined by the ACC/AHA/ESC Guidelines for the Management of Patients with Atrial
Fibrillation) nor CAD. To address and overcome these challenges, PPD
has proposed an educational and observational research approach to improve
physician implementation of the ACC/AHA/ESC
Guidelines and provide market experience with Rythmol SR. PPD
understands that this approach has met with approval from Reliant’s Expert
Advisory Panel for Rythmol SR. Following Reliant’s review of this detailed
proposal, PPD welcomes the opportunity to engage in additional discussions to
refine the implementation assumptions, program considerations and budget
estimates for the program.


We believe the information contained within this revised proposal will
illustrate our expertise and capabilities, as well as confirm our enthusiasm
for assisting Reliant with this program. For further information or
clarification, please contact Dave Provost, Executive Director, Registries and
Observational Studies at 919-462-4104 or Dave.Provost@rtp.ppdi.com.


 


5

















 


Background


Rythmol SR and Atrial Fibrillation Patient Management


Rythmol SR, propafenone HCI extended release capsules, received
regulatory approval from the U.S. Food and Drug Administration (FDA) in
September 2003 and was launched in February 2004. Rythmol SR has an approved
indication to prolong the time to recurrence of symptomatic AF in patients
without structural heart disease.


ACC/AHA/ESC Guidelines for the Management of Patients
with Atrial Fibrillation consider propafenone to be a
treatment option for AF patients (a) without (or with minimal) heart disease;
or (b) with hypertension, but with left ventricular hypertrophy (LVH) less than
1.4 cm. ACC/AHA/ESC Guidelines do
not suggest propafenone for patients with heart failure, with coronary artery
disease (CAD) or with hypertension and LVH greater than or equal to 1.4 cm.


Current management of these patients is complicated by the widespread,
off-label use of amiodarone for AF treatment in patients with both structural
and non-structural heart disease. Despite its lack of an approved indication
for AF, amiodarone has become the gold standard for AF treatment. Even
amiodorane’s less than favorable long-term safety profile1 (with
potential adverse effects such as extreme photosensitivity, pulmonary toxicity,
polyneuropathy, bradycardia, hepatic toxicity and thyroid dysfunction) has not
detracted from its widespread use in treating AF.


Reliant and its Expert Advisory Panel hypothesize that cardiologists
prescribe amiodarone for its effectiveness in treating AF but have a lack of
awareness of amiodarone’s long-term safety profile; this is likely due to the
fact that prescribing cardiologists typically are not involved in the treatment
of the adverse effects experienced by amiodarone patients.


Patient Management Challenges


PPD’s Proposed Program


To improve AF patient management through the proper use of available
AAD products, Reliant must [* * *].


It is PPD’s experience that improved physician management of AF
patients can be achieved through a well-designed educational and observational
research program.   The educational
and  research objectives include: [* * *].


______________


1 Pacerone® (amiodarone
HCI) Tablets package insert. June 2004 revision.


[* * *]:  Certain information on
this page has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


6

















 


To achieve the stated educational and research objectives described
above, PPD’s proposed program will include [* * *].


To ensure that program benefits are fully realized, PPD further
proposes an [* * *].


______________


[* * *]: 
Certain information on this page has been omitted and filed separately
with the Commission.  Confidential
treatment has been requested with respect to the omitted portions.


 


7

















 


	
  Registry
  Synopsis

  	
   

  	
   

  
	
  Study
  Title

  	
   

  	
  Reliant AFFECTS
  Program

  
	
  Indication

  	
   

  	
  Atrial
  fibrillation

  
	
  Design

  	
   

  	
  [* * *]

  
	
  Objectives

  	
   

  	
  Scientific:
  [* * *]

  
	
   

  	
   

  	
  Educational:
  [* * *]

  
	
  Study
  Methodology

  	
   

  	
  [* * *]

  



 


______________


[* * *]: 
Certain information on this page has been omitted and filed separately
with the Commission.  Confidential
treatment has been requested with respect to the omitted portions.


 


8

















 


	
   

  	
   

  	
  [* * *]

  
	
  Participating Physicians

  	
   

  	
  [* * *]

  
	
  Enrolled Patients

  	
   

  	
  [* * *]

  
	
  Patient Follow-Up

  	
   

  	
  [* * *]

  



 


______________


[* * *]: 
Certain information on this page has been omitted and filed separately
with the Commission.  Confidential
treatment has been requested with respect to the omitted portions.


 


9

















 


Project
Considerations


The following considerations and assumptions have been used by PPD in
the preparation of this revised proposal and estimated budget and reflect PPD’s
understanding of the scope of services as per the discussions held with
Reliant. As these considerations are the basis for our resource, timeline and
budget estimates, changes may require an update to this revised proposal. PPD
welcomes the opportunity to revisit the proposal budget if any of its
assumptions are not in line with Reliant’s objectives for this program.


General Considerations


The AFFECTS Program combines physician education regarding the current AHA/ACC/ESC Guidelines for the Management of Patients
with Atrial Fibrillation with an observational registry of physician
practice regarding the real-world treatment of atrial fibrillation.


Physician education will
be provided through a number of registry kick-off meetings, one-on-one
conference calls and via a series of ongoing physician communications.


The registry will be
designed as a [* * *].


As the registry will be
observational in nature and not direct patient care via a specific protocol, PPD
has assumed that the [* * *].


The registry is a US study to be conducted with a mix of
community-based and academic physicians.


PPD has proposed a six-month enrollment period and a per-patient
follow-up of twelve months. Data will be provided for each patient at the time
of enrollment, and then again at approximately three, six, nine and twelve
months post enrollment. As no exact visit schedule will be required by the
registry protocol, it has been assumed that follow-up data will be accepted +/-
45 days around each expected follow-up milestone.


A flow diagram for the
registry is included in Appendix A.


PPD’s scope of services include:


Overall project
management


Management of multiple
group meetings (“investigator meetings”)


Development and
implementation of educational programs


Development and
implementation of pre-/post-registry physician surveys


Development of the
registry data collection forms


Clinical management of
the registry (physician recruitment, IRB processing, site training, ongoing
site management and enrollment support)


______________


[* * *]:  Certain information on
this page has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


10

















 


Development of a web-based electronic data collection
(EDC) system (PPD GlobalView)


Data analysis


Report writing


The PPD Health Outcomes and Clinical Operations groups will collaborate
with Reliant on the development of the registry design and to develop/select
appropriate data collection forms.


Kick-Off Meeting Considerations


During a meeting between Reliant and PPD, several scenarios for raising
awareness and increasing compliance among physicians with the AHA/ACC/ESC Guidelines were discussed.


Based on these
discussions, PPD has proposed that physicians be recruited for participation in
the AFFECTS Program and be invited to a face-to-face meeting as part of the
registry startup process. This approach offers the benefit of a standardized
forum for pre-study survey implementation, EDC tool and study procedures
training, as well as treatment guidelines education.


To reach the broader
physician community, PPD will work with Reliant to develop one or more programs
that can be presented in conjunction with appropriate professional meetings
(e.g., ACC Annual Scientific Session). These programs will be a combination of
educational programs and information gathering such that the key learnings
derived from the meeting(s) can be presented back to an even broader physician
audience.


As the registry database
becomes more robust, it will also be possible to present registry findings
during a main conference session and thus educate physicians without the need
to provide grants for meeting attendance.


PPD has proposed the following meeting format:


Three regional meetings


Attendees will arrive on
Friday afternoon in time for an evening reception and dinner.


It has been assumed that
attending physicians will be accompanied by a study coordinator (two attendees
per site).


Saturday morning will be
devoted to therapeutic and treatment guidelines discussions.


Saturday afternoon will
focus on operational issues regarding the registry and the use of the EDC tool
for all data collection.


Breakfast and lunch,
along with refreshments at breaks, will be provided on Saturday.


It is anticipated that
the meeting will adjourn no later than 4:00pm on Saturday.


PPD has estimated that approximately 30 to 50 percent of participating
physicians will attend one of the meetings. Physicians who are unable to


 


11

















 


attend one of the group meetings will be required to attend a web cast
training session regarding the AHA/ACC/ESC
Guidelines as part of their registry training.


As an alternative to the
face-to-face group meetings, all physicians could be trained via web cast
sessions. This alternative approach would result in significant cost savings
(potentially in excess of $[* * *]).


PPD will be responsible for developing the meeting agenda and meeting
materials to be presented and/or provided to attendees with the exception of
the AHA/ACC/ESC Guidelines
training materials; the Guidelines materials will be developed by Interquest.
Reliant will approve all materials.


PPD will work with
Interquest to ensure that the Guidelines presentation materials are consistent
in format with other meeting materials.


Through its meeting planning partner, PPD will also be responsible for
all meeting logistics, including travel arrangements for all attendees.


PPD has assumed that one or more members of Reliant’s Rythmol SR
advisory board will lead the discussions concerning the treatment guidelines at
each of the meetings. PPD believes these advisors will add immense credibility
to the discussions and maximize their acceptance by participating physicians.
PPD understands that Interquest will be responsible for preparing these
advisors for the meetings.


PPD will lead the registry implementation discussions, including the
use of the study’s web-based data collection tools.


Prior to the start of the educational portions of the meetings, PPD [*
* *].


A similar survey will be
conducted at the conclusion of the conduct of the registry and a pre/post
analysis will be conducted.


Clinical Considerations


The scope of PPD’s clinical responsibilities for the registry will
include overall project management, physician recruitment, site training and
management, IRB processing, grant administration, enrollment support and
distribution of ongoing communications materials and reports.


PPD will be responsible for recruiting participating physicians. PPD
has assumed that Reliant will provide it with a list of prescribing physicians
to target for its recruitment efforts.


PPD has assumed that
Reliant will provide PPD with a list of approximately 6,000 potential
physicians. It is PPD’s experience that only one in ten to 12 physicians
contacted about participation in post-marketing research programs ultimately
participates.


PPD will provide Reliant with a template participation agreement for
use with registry participants. The simple agreement will define the
requirements of participation and outline the grant schedule. PPD has assumed
that all


______________


[* * *]:  Certain information on
this page has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


12

















 


physicians will use the same agreement and that negotiation will not
take place on a site-by-site basis. PPD will initiate all agreement discussions
with participating sites, but Reliant will be responsible for all approvals.


PPD has assumed the use of a central IRB for 90% of the participating
physicians; a site-specific local IRB has been assumed for the remaining sites.


The central IRB is
expected to review and approve the protocol/procedures document and informed
consent form; no site-level review of documents is anticipated.


Local IRBs will likely
require additional document submissions. PPD will assist sites requiring the
use of a local IRB with the preparation of their submission.


PPD will provide follow-up training to each site’s staff on the
registry procedures once IRB approval has been obtained. All site training will
be conducted via scheduled teleconferences. PPD will provide each site with an
AFFECTS Program Reference binder that contains all of the information and
materials necessary for it to successfully participate in the registry.


PPD will train each site on the use of the EDC system, including how to
enter data for a new patient, how to complete follow-up eCRFs for existing
patients and how to edit existing data, as necessary, to resolve outstanding
queries.


To support the enrollment efforts of participating sites and to ensure
sites follow the approved registry procedures for data collection, PPD will
maintain monthly contact with the sites via telemonitoring calls; no on-site
visits are planned for the registry.


The PPD clinical team will perform a brief online review of all eCRFs
to check for proper completion and ensure missing data are kept to a minimum.


eCRFs will be reviewed
online using tools within the EDC system.


PPD will review
completion of the adverse event eCRFs for each visit.


PPD has assumed limited
query generation, an average of just two per patient, with only a limited list
of critical data points to be queried.


PPD has assumed that it will administer grant payments to physicians.
PPD has assumed a study startup grant of $[* * *] per participating
physician. In addition, a grant of $[* * *] per patient visit has
been included. For patients completing the one-year follow-up observation,
physicians will be paid a total grant of $[* * *] ($[* * *]
each for the Baseline/Enrollment visit plus four follow-up visits); pro-rated
amounts will be paid for patients completing only part of the follow-up.


PPD has used these
estimated grants to provide Reliant with a sense of potential grant budget. PPD
will work with Reliant to finalize these estimates.


PPD anticipates
administering payments on a quarterly basis throughout the registry’s
enrollment/follow-up period.


 






[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


13

















 


Clinical Staffing Considerations


PPD will assign a 1.0 FTE
Project Manager during the registry’s setup period (three months) and physician
recruitment period (four months). The PM will then ramp down to 0.50 FTE for
the duration of the patient enrollment and follow-up periods (15 months). The
PM will be assigned as a 0.25 FTE during study closeout (two months).


A 1.25 FTE CRA will be
assigned during the setup period to assist the PM will project setup
activities. During the physician recruitment period, up to 6.5 CRA FTEs will be
deployed. An average of 3.0 CRA FTEs will be assigned to manage the registry
for the balance of the patient enrollment and follow-up periods.


A 0.5 FTE Research Assistant
will be assigned during the project setup and physician recruitment periods to
assist the PM and CRA(s) with administrative matters. This resource will also
be available on ~0.10 FTE basis for the duration of the registry.


A Clinical Director will
oversee the registry staff and provide senior-level direction throughout the
implementation of the program. The Director will be assigned at ~0.05 FTE.


Data Management Considerations


PPD will implement its web-based electronic data collection (EDC)
solution for the AFFECTS Program — PPD GlobalView. PPD GlobalView has served as
the web-based EDC solution for more than 20 studies, including multinational
registries. To date, the system has been used by more than 500 sites, in 21
countries, to enter and manage data for over 25,000 patients.


The system will require
no special software at each participating site, other than a standard web
browser and Internet connection, and will feature an easy-to-use, intuitive
interface.


Additional background
information about PPD GlobalView is provided in Appendix D.


PPD GlobalView will be deployed for the collection of all registry data
(enrollment and follow-up), as well as for the collection of the post-registry
survey data.


The system will also be
setup to collect pre-registry survey data from physicians who were unable to
attend one of the group training meetings. PPD will enter the survey data
collected during the group meetings into the EDC system.


PPD has assumed that all participating physicians will be capable of
using a web-based EDC solution. PPD will work with sites that are unable to use
the tool on a case-by-case basis.


A supplemental budget may
be necessary to manage PPD’s manual entry of data from these physicians.


 


14

















 


The PPD Health Outcomes group will work with Reliant to design/develop
the registry’s case report forms (CRFs), assuming the lead role. Once the CRF
data elements are approved by Reliant, PPD will create the on-screen eCRFs.


PPD has assumed the design/development of the following eCRFs:


[* * *]


[* * *]


[* * *]


[* * *]


The total number of eCRFs per completed patient has been assumed to be [*
* *].


The eCRF for the collection of adverse events has been assumed to
include a pick list of expected/most common adverse events for this patient
population. The form will also include an “Other” option for which the
physician will specify the event.


PPD has assumed the
adverse event data will be coded for consistency prior to analysis. Costs for
this coding have been included.


Automated, real-time edit checks will be built into the system to
provide immediate data entry feedback to site personnel using the system. The
edit checks will catch most data entry errors, as well as potentially
inaccurate data points, and thus greatly minimize the number of queries
generated per patient.


PPD Data Management will provide documentation and data review support
as in a paper-based process to ensure data quality.


Data Management will draft database specifications for Reliant and
create final specifications to be used in the creation of the eCRF. These
specifications will include the eCRF content and data edit/review programs.


PPD will perform User Acceptance Testing and review results with
Reliant for final approval before the system is made available for use by
participating physicians.


Data Management will provide additional support for comprehensive data
review via listings and specialized output to address items that may not be
efficiently addressed in the automatic edits in the EDC system. These items
will be specified in the Data Validation Manual.


PPD will provide Data Management and EDC Coordination support to the
project team. This support is in the form of assistance to the site and
monitors on eCRF issues, management metrics to track study progress and
additional data review steps.


PPD will assign an EDC Manager to provide process support to the
AFFECTS Program. The EDC Manager position is designed to support both internal
project teams and external vendors and/or Reliants throughout all phases of
registry conduct. Responsibilities include the participation in and/or review
of user acceptance testing, project team training and the oversight of


______________


[* * *]:  Certain information on
this page has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


15

















 


change control items that could affect the final
deliverables of the contract. This would include identifying best practices and
processes to be built around the EDC system to be used, as well as aiding in
troubleshooting any problems encountered by the team.


Initial EDC system training will take place during the large group
meetings; additional one-on-one training will be conducted via scheduled
telephone conferences.


Costs for setting up
equipment for the training at the group meetings will be a pass through expense
associated with each meeting.


The clinical team managing the AFFECTS Registry will provide the
front-line support for site questions concerning the proper use of the EDC
system. Users experiencing technical difficulties will be triaged to the PPD
GlobalView technical Help Desk. Technical support will be available from 8:00am
through 8:00pm (Eastern).


Additional after hours
support coverage is available at additional cost. It is PPD’s experience,
however, that extended coverage is typically not necessary for studies
conducted within the typical outpatient setting operating during normal
business hours.


Occasionally, study sites
will have technical issues that are independent of the EDC system. These
include local networking and Internet access issues, and local hardware or
system failures. These issues are typically the responsibility of the site’s
local IT support services (as available). Reliant and PPD will work together to
determine the appropriate approach for providing such general IT support to the
registry participants on a case-by-case basis.


PPD has assumed that the registry database will not require the import
of external electronic data sets (e.g., central lab transfers).


Data Analysis Considerations


The PPD Health Outcomes group, a specialized unit within PPD’s
Biostatistics department focused on health outcomes, quality of life research,
pharmacoeconomics and pharmacoepidemiology, will assign a Lead Health Outcomes
Scientist who will collaborate with Reliant to provide the following documents
and services:


Physician Survey Program


Develop pre- and
post-education physician surveys


Develop statistical
analysis plan for survey analyses


Conduct analysis of data;
prepare statistical tables


Prepare summary report of
survey findings


Registry


Develop statistical
analysis plan for all planned analyses


Conduct quarterly
analyses for personalized and aggregate reports


Conduct interim and final
analyses; prepare statistical tables


Prepare final summary
report of registry findings


 


16

















 


Optional services:
manuscript and abstract preparation


For this project, a “document” is defined as the (1) survey
instruments, (2) procedures document (protocol), (3) statistical analysis plan
or (4) summary report. For all “documents”, one draft document will be provided
to Reliant for input and review. Upon return of consolidated comments from
Reliant, PPD will update the document to become the final document for
Reliant’s approval. Further revision cycles to become approved, or revisions to
an approved document would result in increased costs from those stated in this
proposal.


For all documents provided to Reliant for review/input, PPD assumes
that Reliant will consolidate their comments from all Reliant reviewers into a
single set of comments for PPD’s use in revising the document. We ask for this
because it is sometimes the case that two Reliant reviewers provide
contradictory comments or suggestions. In this case, we need for Reliant to
resolve these potential conflicts internally for PPD to proceed in an
expeditious manner with the document revision.


Physician Survey Program


An abbreviated statistical analysis plan will be written for the survey
analyses. The SAP will include a plan for database manipulation, selection or
creation of key variables, as well as a shell, or template, for each table and figure.
This SAP must be approved by Reliant before any programming can begin. Once the
SAP is approved, detailed programming specifications will be prepared to guide
the programming efforts.


Counts of proposed tables and listings are specified below. These
counts were estimated based on the assumption that all data will come from two
questionnaires plus demographic data. However, expectations for numbers of
tables can vary significantly from Reliant to Reliant. As such, this is only an
estimate based on our experience with this type of study.


 




	
   

  	
   

  	
  Uniques2

  	
   

  	
  Repeats

  	
   

  	
  Total

  	
   

  
	
  Tables

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  
	
  Listings

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  
	
  Figures

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  
	
  Total

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  










2                               A “unique” table,
listing or figure is defined as one having a different layout of information in
the body of the table. Unique tables require custom layout design, custom
written specifications, custom programming and custom quality review, in
contrast, a “repeat” table uses the same table layout as another table, but may
have different subtitles or footnotes, or use different subsets of data. As a
result, the cost to prepare “repeat” tables is much less than the cost to
prepare “unique” tables. Finalization of the statistical analysis plan may
result in more or fewer tables or listings than projected above. At
finalization of the SAP, the budget for these analyses will be adjusted if the
estimates above are not within +/- 5% of the actual number of tables, listings
and figures.


[* * *]:  Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


17

















 


This proposal assumes one draft and one final version of the summary
tables. Draft tables will be delivered for Reliant review within four weeks of
database lock. These analyses can be conducted incrementally (i.e., after each
survey (pre- and post-)) or at a single time at then end of the program. (If
incrementally, table and listings counts are cumulative across both analyses).


The above table, listing and figure counts are based on the assumption
that the following survey objectives will be explored:


[* * *]


Specifically, it is anticipated that several of the following topic
areas will be explored statistically. Survey development and associated
discussion and collaboration will likely expand these content areas:


[* * *]


The large sample of physicians will allow exploration of several subgroups.
Subgroups of interest may include: [* * *]


______________


[* * *]:  Certain information on
this page has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


18

















 


Registry


A single statistical analysis plan will be written for all registry
analyses including personalized and aggregate reports. The SAP will include a
plan for database manipulation, selection or creation of key variables as well
as a shell, or template, for each table and figure. This SAP must be approved
by Reliant before any programming can begin. Once the SAP is approved, detailed
programming specifications will be prepared to guide the programming efforts.


Counts of proposed tables for the registry analyses are listed. The
assumptions described above for survey data analysis apply to registry data
analysis as well.


 




	
   

  	
   

  	
  Uniques

  	
   

  	
  Repeats

  	
   

  	
  Total

  
	
  Tables 

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  
	
  Listings

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  
	
  Figures

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  
	
  Total

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  	
  [* * *]

  






An interim analysis will be conducted when approximately 2,500 patients
(50 percent) have completed six months in the registry.


The interim analysis will include [* * *].


This proposal assumes one draft and one final version of the summary
tables and listings for each analysis (interim and final). Draft tables for the
final analysis will be delivered for Reliant review within four weeks of
database lock.


To help maintain physician interest and support for the registry, as
well as maintain physician awareness of Reliant’s Reliantship of the registry,
PPD has proposed an ongoing communications program throughout the conduct of
the registry.


Quarterly aggregate
summary reports of the registry data [* * *].


Semi-annual personalized
reports will [* * *].


______________


[* * *]:  Certain information on
this page has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


19

















 


[* * *]


Serious Adverse Event Reporting Considerations


PPD will instruct each participating physician on the appropriate
reporting mechanisms for the reporting of serious adverse events in patients
enrolled in the AFFECTS Registry:


Use of FDA MedWatch form


Contacting product
manufacturer


PPD will provide participating physicians with training on this topic
during the registry initiation meetings, the one-on-one training calls and
periodically throughout the conduct of the registry.


Project Team Communications Considerations


Real-time registry enrollment reports will be available to Reliant from
the EDC system. The system will enable the Reliant AFFECTS Registry management
team to view aggregate enrollment metrics, as well as center/physician specific
details.


No confidential
patient-level data will be available to Reliant.


PPD will use its proprietary ClinTrack study management system to
manage all of the administrative data associated with the conduct of the
registry; all data used to manage the participating sites throughout the
conduct of the registry will be stored in this system.


The system manages all
site contact information, site status information (e.g., IRB Approval Pending,
Active, Closed), IRB approval details, regulatory document tracking, site
training metrics, grant payment tracking, phone contacts and communications
logs (fax, email, letter, etc.).


ClinTrack will be used to
produce most of the study metrics reports provided to Reliant to keep it up to
date on the current status of the registry. These reports will be posted to the
PPD DirectConnectTM web site each day and will be available to the Reliant
registry management team on a 24/7 basis.


PPD will develop a PPD DirectConnectTM site for the registry. PPD
DirectConnectTM is PPD’s secure, web-based study information portal for timely,
efficient management and support of study communications.


The proposed PPD
DirectConnect site is intended for use by the Reliant and PPD registry management
teams; it will not be a public information portal.


PPD will work with
Reliant to determine the specific content for the site and will deliver a
custom site specifically tailored to the needs of the AFFECTS Registry.


All site content will be
updated on a timely, scheduled basis, consistent with the study’s data flow and
needs.


______________


[* * *]:  Certain information on
this page has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


20

















 


PPD takes the confidential nature of project communications very
seriously. PPD DirectConnectTM has the following features that ensure
confidentiality and security:


Use of a dedicated
server, on a DMZ (demilitarized zone) segregated from the main PPD network and
behind the corporate firewall;


Authentication of users
with user-specific names and passwords;


Authorization of
authentic users to project-appropriate web addresses;


Restricted access only to
those participating in the study;


Encryption of all traffic
to/from the web server by a Verisign server certificate with SSL (secure
sockets layer) technology;


Monitoring of all traffic
and tracking of hits;


Access to web site by
only authorized users (i.e., registry management teams)


Miscellaneous Considerations


PPD has provided estimated shipping costs associated with site
recruitment, regulatory document collection and the distribution of the AFFECTS
Program materials. Actual costs will be passed through to Reliant on a monthly
basis as incurred.


PPD has provided estimated costs for the production of the AFFECTS
Program Reference Binder. Actual costs will be passed through to Reliant.


PPD project-related travel requested by Reliant will be passed through
to Reliant as the trips occur; Reliant will pre-approve all PPD project travel.


 


21

















 


Timeline


The following is an estimated timeline for the implementation of the
AFFECTS Program. Timelines adjustments will be made once the final program
design and scope have been determined in conjunction with Reliant. A graphical
depiction of timing of program activities is provided in Appendix C.


 


	
  Task

  	
   

  	
  Duration

  	
   

  	
  Timeline*

  
	
  Program Setup

  	
   

  	
  3.0 months

  	
   

  	
  Jan-05 — Mar-05

  
	
  Physician Recruitment/Training/ 

  IRB Processing and 

  Kick-Off Meetings

  	
   

  	
  4.0 months

  	
   

  	
  Apr-05 — Jul-05

  
	
  Patient Enrollment

  	
   

  	
  6.0 months

  	
   

  	
  May-05 — Oct-05

  
	
  Data Collection 

  (12 months per patient)

  	
   

  	
  18.0 months

  	
   

  	
  May-05 — Oct-06

  
	
  Study Closeout

  	
   

  	
  2.0 months

  	
   

  	
  Nov-06 — Dec-06

  
	
  Database Lock

  	
   

  	
  1.0 week

  	
   

  	
  Nov - 06

  
	
  Final Data Analysis/Report

  	
   

  	
  2.0 months

  	
   

  	
  Nov-06 — Dec-06

  
	
  Total PPD Involvement

  	
   

  	
  24
  months

  	
   

  	
  Jan-05
  – Dec-06

  



*Note: Timeline segments overlap.


 


22

















 


Budget


The budget presented reflects the services outlined in this revised
proposal and are based on PPD’s current understanding of the project’s scope.
After more detailed discussions of the project with Reliant, if required, PPD
will update the estimated budgets to better reflect the AFFECTS Program’s final
requirements.


 


	
  DIRECT
  COSTS

  	
   

  	
   

  
	
  Clinical

  	
   

  	
   

  
	
  Project
  Management

  	
   

  	
  $[* * *]

  
	
  Project Setup

  	
   

  	
  $[* * *]

  
	
  Staff Training

  	
   

  	
  $[* * *]

  
	
  Site Management
  and Support

  	
   

  	
  $[* * *]

  
	
  Regulatory
  Document and File Management

  	
   

  	
  $[* * *]

  
	
   

  	
   

  	
   

  
	
  TOTAL
  CLINICAL COSTS

  	
   

  	
  $[* * *]

  
	
   

  	
   

  	
   

  
	
  Information
  Systems

  	
   

  	
   

  
	
  PPD Direct
  Connect(TM) Set-up

  	
   

  	
  $[* * *]

  
	
  PPD Direct
  Connect(TM) Maintenance

  	
   

  	
  $[* * *]

  
	
  ClinTrack Set-up

  	
   

  	
  $[* * *]

  
	
  ClinTrack
  Maintenance

  	
   

  	
  $[* * *]

  
	
   

  	
   

  	
   

  
	
  TOTAL
  INFORMATION SYSTEMS COSTS

  	
   

  	
  $[* * *]

  
	
   

  	
   

  	
   

  
	
  Data
  Management

  	
   

  	
   

  
	
  Set up Database

  	
   

  	
  $[* * *]

  
	
  Maintain
  Database

  	
   

  	
  $[* * *]

  
	
  Total Document
  Management

  	
   

  	
  $[* * *]

  
	
  Data Review and
  Clean-up

  	
   

  	
  $[* * *]

  
	
  Import External
  Data

  	
   

  	
  $[* * *]

  
	
  Transfer
  Database

  	
   

  	
  $[* * *]

  
	
  Project
  Management

  	
   

  	
  $[* * *]

  
	
   

  	
   

  	
   

  
	
  TOTAL
  DATA MANAGEMENT COSTS

  	
   

  	
  $[* * *]

  







[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


23

















 


 


	
  Electronic
  Data Capture

  	
   

  
	
  EDC System
  Requirements Documentation (Project Definition)

  	
  $[* * *]

  
	
  Database
  Requirements Design And System Build

  	
  $[* * *]

  
	
  Forms Controls
  Implementation (data review and validation)

  	
  $[* * *]

  
	
  Data Transfer
  Functionality (reporting), Database finalization

  	
  $[* * *]

  
	
  Site Initiation
  and Training

  	
  $[* * *]

  
	
  Help Desk
  Support (EDC)

  	
  $[* * *]

  
	
  Project
  Management

  	
  $[* * *]

  
	
  System
  Maintenance & Security Data Storage and Maintenance

  	
  $[* * *]

  
	
  Import External
  Data

  	
  $[* * *]

  
	
  Ongoing Project
  Maintenance

  	
  $[* * *]

  
	
  TOTAL
  ELECTRONIC DATA CAPTURE

  	
  $[* * *]

  
	
  Health
  Outcomes

  	
   

  
	
  Monthly
  Maintenance

  	
  $[* * *]

  
	
  Tables,
  Listings, and Figures

  	
  $[* * *]

  
	
  SAP text and TLF
  shells

  	
  $[* * *]

  
	
  Final CSR text

  	
  $[* * *]

  
	
  Survey Program

  	
  $[* * *]

  
	
  Quarterly
  Aggregate and Semi-Annual Personalized Reports

  	
  $[* * *]

  
	
  TOTAL
  HEALTH OUTCOMES COSTS

  	
  $[* * *]

  
	
  TOTAL
  DIRECT COSTS

  	
  $[* * *]

  
	
  OPTIONAL COSTS1

  	
   

  
	
  Abstract

  	
  $[* * *]

  
	
  Manuscript

  	
  $[* * *]

  
	
  Communications
  Plan Summary Table

  	
  $[* * *]

  
	
  TOTAL OPTIONAL COSTS

  	
  $[* * *]

  







[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


24

















 


 


	
  Pass
  Through Costs

  	
   

  
	
  IRB
  Reimbursement

  	
  $[* * *]

  
	
  Clinical Grants

  	
  $[* * *]

  
	
  Phone/Fax

  	
  $[* * *]

  
	
  Study Kits:
  Design/Layout and Production

  	
  $[* * *]

  
	
  Postage

  	
  $[* * *]

  
	
  Study Initiation
  Meetings (3)

  	
  $[* * *]

  
	
  Physician
  Training Webcast

  	
  $[* * *]

  
	
  TOTAL
  PASS THROUGH COSTS

  	
  $[* * *]

  
	
  TOTAL
  COSTS

  	
  $[* * *]

  



Note 1: Optional Costs not included in the total costs.






[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


25

















 


Payment Schedule


 


	
  Milestone*

  	
   

  	
  Payment
  

  Amount

  	
   

  	
  Estimated

  Completion

  	
   

  
	
  Direct
  Costs

  
	
  Execution of
  Contract

  	
   

  	
  $[* * *]

  	
   

  	
  Q1 2005

  	
   

  
	
  Monthly
  Management $[* * *] per month; 23 months

  (Feb-05 – Dec-06)

  	
   

  	
  $[* * *]

  	
   

  	
   

  	
   

  
	
  Clinical

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  First Site
  Initiated

  	
   

  	
  $[* * *]

  	
   

  	
  Q1 2005

  	
   

  
	
  Last Site
  Initiated

  	
   

  	
  $[* * *]

  	
   

  	
  Q3 2005

  	
   

  
	
  First Patient
  Enrolled

  	
   

  	
  $[* * *]

  	
   

  	
  Q2 2005

  	
   

  
	
  25% of Patients
  Enrolled

  	
   

  	
  $[* * *]

  	
   

  	
  Q3 2005

  	
   

  
	
  50% of Patients
  Enrolled

  	
   

  	
  $[* * *]

  	
   

  	
  Q3 2005

  	
   

  
	
  75% of Patients
  Enrolled

  	
   

  	
  $[* * *]

  	
   

  	
  Q3 2005

  	
   

  
	
  All Patients
  Enrolled

  	
   

  	
  $[* * *]

  	
   

  	
  Q4 2005

  	
   

  
	
  All Sites
  Closed-out

  	
   

  	
  $[* * *]

  	
   

  	
  Q4 2006

  	
   

  
	
  Final Report
  Delivered

  	
   

  	
  $[* * *]

  	
   

  	
  Q4 2006

  	
   

  
	
  Data Management

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Database Setup

  	
   

  	
  $[* * *]

  	
   

  	
  Q2 2005

  	
   

  
	
  50% of CRFs Entered

  	
   

  	
  $[* * *]

  	
   

  	
  Q2 2006

  	
   

  
	
  100% of CRFs
  Entered

  	
   

  	
  $[* * *]

  	
   

  	
  Q4 2006

  	
   

  
	
  Database Lock

  	
   

  	
  $[* * *]

  	
   

  	
  Q4 2006

  	
   

  
	
  Biostatistics

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Draft Analysis
  Plan

  	
   

  	
  $[* * *]

  	
   

  	
  Q2 2005

  	
   

  
	
  Final Analysis
  Plan

  	
   

  	
  $[* * *]

  	
   

  	
  Q3 2005

  	
   

  
	
  Draft Tables
  & Listings

  	
   

  	
  $[* * *]

  	
   

  	
  Q3 2006

  	
   

  
	
  Final Tables
  & Listings

  	
   

  	
  $[* * *]

  	
   

  	
  Q4 2006

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total
  Direct Costs

  	
   

  	
  $[* * *]

  	
   

  	
   

  	
   

  







[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


26

















 


	
  Milestone

  	
   

  	
  Payment

  Amount

  	
   

  	
  Estimated

  Completion

  	
   

  
	
  Pass-Through
  Costs

  
	
  Study Initiation
  Meetings

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Due at Execution
  of Contract

  	
   

  	
  $[* * *]

  	
   

  	
  Q1 2005

  	
   

  
	
  Invoiced
  Quarterly in Advance of Payout

  	
   

  	
  $[* * *]

  	
   

  	
  Q1 2005

  	
   

  
	
  Clinical Grants
  and IRB Fees**

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Due at Execution
  of Contract

  	
   

  	
  $[* * *]

  	
   

  	
  Q1 2005

  	
   

  
	
  Invoiced
  Quarterly in Advance of Payout

  	
   

  	
  $[* * *]

  	
   

  	
  2005

  	
   

  
	
   

  	
   

  	
  $[* * *]

  	
   

  	
  2006

  	
   

  
	
  Remaining
  Pass-Through Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Invoiced
  Quarterly in Advance of Payout

  	
   

  	
  $[* * *]

  	
   

  	
  2005

  	
   

  
	
   

  	
   

  	
  $[* * *]

  	
   

  	
  2006

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Annual
  Pass-Through Costs

  	
   

  	
  $[* * *]

  	
   

  	
  2005

  	
   

  
	
   

  	
   

  	
  $[* * *]

  	
   

  	
  2006

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total
  Pass-Through Costs

  	
   

  	
  $[* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Project
  Total

  	
   

  	
  $[* * *]

  	
   

  	
   

  	
   

  







*                                                   In
the event the registry is delayed or put on hold for a period greater than 30
days, PPD will invoice Reliant on a
pro-rated basis for all milestones that are partially completed


**                                            PPD
will not release payment for physician grants until Reliant has remitted the
applicable amount


[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


27

















 


Appendix
A: Registry Flow Diagram


Refer to the attached flow diagram for an overview
of the registry’s physician-patient interaction points and PPD’s process
management.


 


Activity Schedule: AFFECTS Registry

(within framework of a single patient)


 




	
   

  	
  Month 0

  	
  Months 1 - 2

  	
  Month 3 +/- 45 Days

  	
  Months 4 - 5

  	
  Month 6 +/- 45 Days

  	
  Months 7 - 8

  	
  Month 9 +/- 45 Days

  	
  Months 10 - 11

  	
  Month 12 +/- 45 Days

  
	
  PHYSICIAN
  ACTIVITIES

  	
  [* * *]

  	
   

  	
  [* * *]

  	
  [* * *]

  	
   

  	
  [* * *]

  	
  [* * *]

  	
   

  	
  [* * *]

  	
  [* * *]

  	
   

  	
  [* * *]

  	
  [* * *]

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  PPD
  MANAGEMENT

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]  

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  










[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


28

















 


Appendix B: Overall AFFECTS Program Flow Diagram


Refer to the attached flow diagram for an overview of the AFFECTS
Program.


 


AFFECTS Program: Flow
Diagram


 


	
  PHYSICIAN

  	
  Agree to

  Participate in

  Education &

  Registry Program

  	
   

  	
   

  	
  Receive 

  Training

  & Complete Pre-

  Registry Survey

  	
  Receive 

  Summary

  of Survey 

  Results

  	
  Participate

  in

  Registry

  	
  Complete
  Post-

  Registry
  Survey

  	
   

  	
   

  	
  Receive

  Practice-Level

  Report

  	
  Receive

  Aggregate

  Summary 

  Report

  	
   

  	
   

  
	
  PPD

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  	
  [* * *]

  







[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


29

















 


Appendix C: Graphical
Depiction of Timeline


Refer to the attached flow diagram for a
graphical overview of the proposed program timeline.


 


Implementation Schedule:
AFFECTS Program


 


	
   

  	
  Month

  -2

  	
  Month

  -1

  	
  Month

  1

  	
  Month

  2

  	
  Month

  3

  	
  Month

  4

  	
  Month

  5

  	
  Month

  6

  	
  Month

  7

  	
  Month

  8

  	
  Month

  9

  	
  Month

  10

  	
  Month

  11

  	
  Month

  12

  	
  Month

  13

  	
  Month

  14

  	
  Month

  15

  	
  Month

  16

  	
  Month

  17

  	
  Month

  18

  	
  Month

  19

  	
  Month

  20

  	
  Month

  21

  	
  Month

  22

  	
  Month

  23

  	
  Month

  24

  	
  Month

  25

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  RELIANT AND RELIANT
  ADVISORY PANEL

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [* * * *]

  	
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  [* * * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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  PPD

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
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  [* * * *]

  	
   

  	
   

  	
   

  	
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  [* * * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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  [* * * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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  [* * * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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  [* * * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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  [* * * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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  [* * * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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  [* * * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


30

















 


 


Appendix D: PPD GlobalView Details


For this program, PPD has proposed the use of PPD GlobalView. PPD
GlobalView has served as the web-based EDC solution for more than 20 studies,
including multinational registries. To date, the system has been used by more
than 500 sites in 21 countries to enter and manage data for over 25,000
patients.


Each deployment of PPD GlobalView is developed as a project-specific
EDC solution. As such, a core set of components and tools are used to build
each system to meet the needs of individual studies; the development process is
not simply a configuration of a core system. Builds follow established software
development life cycle (SDLC) standards for gathering of user requirements,
creation of system specifications, database development, coding, validation and
user acceptance testing.


Each PPD GlobalView deployment is fully validated before it is placed
into the production environment and released to the user community. A
Validation Plan is created, test scripts are written, a regressive testing
methodology is employed and a Validation Summary Report is created. Each PPD
GlobalView database includes full audit trails on all data elements and is
21CFR11 compliant.


Remote Hardware/Software System Assessment is built in as a feature of
PPD GlobalView. This web-based site assessment tool automates the technical
hardware/software certification process, reducing the time it takes for
physician’s to test their system and ensure compatibility with the EDC site.


 


 


31














 


Modification Number 1


 


Contract Modification to Project
Addendum Dated 31 January 2005


 


	
  Effective Date:

  	
   

  	
  June
  26, 2006

  	
   

  	
  Sponsor:

  	
   

  	
  Reliant
  Pharmaceuticals,

  Inc.

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol Name:

  	
   

  	
  Atrial
  Fibrillation: Focus

  on Effective Clinical

  Treatment Strategies

  (AFFECTS) Registry

  	
   

  	
  Sponsor

  Contact:

  	
   

  	
  Jigna
  Heble, Pharm.D.

  Assistant Director,

  Clinical Development

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  PPD
  Project

  	
   

  	
   

  	
   

  	
  Sponsor
  Contact

  	
   

  	
   

  
	
  Manager:

  	
   

  	
  Rosalyn
  Shaw

  	
   

  	
  Telephone No:

  	
   

  	
  908-860-7017

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Bus
  Dev

  	
   

  	
   

  	
   

  	
  Sponsor
  Contact

  	
   

  	
   

  
	
  Director:

  	
   

  	
  Dominic
  Mancini

  	
   

  	
  Fax No:

  	
   

  	
  908-542-4460

  



 


The original
scope-of-work for the above-referenced project included the enrollment of 5,000
patients
in 500 US centers over a period of 6 months. Based on several months of
enrollment data,
potential changes for the project began being discussed in early September
2005. At the request of Reliant different cost-specification scenarios were
provided.


By early December the decision was reached to
extend the enrollment window by seven months (in
order to achieve an estimated 2,000 enrolled patients). Furthermore, the
sponsor had previously decided that
adverse event data would not be captured as a part of the study database. These changes were accompanied by
appropriate staffing reductions (i.e., the timeline extension includes
0.29 FTEs for 7.0 additional months before closeout, Nov-06 through May-07). The new scope also reflects a reduction
in number of site files created/maintained. Please refer to the
following sections for additional information and detail.


Hence, the Project Addendum by and between PPD
Development, LP, successor in interest to PPD Development, LLC and Reliant
Pharmaceuticals, Inc. effective as of January 31, 2005 (the “Project Addendum”)
regarding the above-referenced Protocol shall be modified as follows:


New Scope Q1 2005 adjusted
per decision not to collect AEs. New Scope
Q42005/2006 includes maintenance of CRA team at 5.0 FTEs Aug-05 through
Dec-05 vs. 2.5 FTEs in Revision #2 budget (Reliant Request),
then reduction of CRA staff from 2.5 FTEs to 2.0 FTEs from Jan-06 through
Oct-06 (lower site/patient counts). Timeline Extension includes 2.0 CRA FTEs
for 7.0 additional months before closeout (Nov-06 through May-07).


New Scope 2006 includes maintenance
of PM at 0.50 FTE through completion of enrollment (May-06), then reduction to 0.40 FTE through Oct-06. Timeline Extension
includes the PM at a 0.40 FTE level for an additiona17.0 months before closeout
(Nov-06 through May-07).


New Scope reflects reduction
in number of site files created/maintained. Timeline Extension includes 0.29
FTEs for 7.0 additional months before closeout (Nov-06 through May-07).


	
  Original
  Contract Value

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Estimated
  savings associated with this Contract Modification:

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Direct Costs are
  INCREASED by:

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Pass-Through
  Costs are DECREASED by:

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Revised
  Estimated Total Project Budget

  	
   

  	
  $

  	
  [* * *]

  	
   

  







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested with
respect to the omitted portions.


1

















 


Modification Number 1


A detailed explanation
of costs has been developed in an Excel spreadsheet (Reliant AFFECTS Program:
Budget Review) is attached hereto as Exhibit A. Payment of such costs shall be
made in accordance with the Revised Payment Schedule attached hereto as Exhibit
B.


Upon execution by the
parties, this Contract Modification will be made a part of the Project Addendum and
incorporated by reference therein. Except as expressly provided herein or in
any other mutual
written agreement by the parties, all terms and conditions contained in the
Project Addendum shall remain in full force and effect. All capitalized terms
used but not otherwise defined herein shall have the meanings ascribed to them
in the Project Addendum.


ACCEPTED AND AGREED:


	
  PPD
  Development, LP

  	
  Reliant
  Pharmaceuticals, Inc.

  
	
  By:
  PPD GP, LLC

  	
   

  	
   

  
	
  Its
  General Partner

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
  Colin
  Shannon

  	
  By:

  	
   Steve Ketchum

  
	
  Name:

  	
  Colin
  Shannon

  	
  Name:

  	
   Steve Ketchum, Ph.D.

  
	
  Title:

  	
  Executive
  Vice President

  	
  Title

  	
  Sr.
  VP, R & D and Medical Affairs

  
	
   

  	
  PPD Global Clinical
  Operations

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  [SEAL]

  



 


 


2

















 


Modification Number 1


 


EXHIBIT A - BUDGET REVIEW


 


	
   

  	
   

  	
  Original

  Contract

  	
   

  	
  New
  Scope

  Q1 2005

  	
   

  	
  New
  Scope

  Q1 2006

  	
   

  	
  Timeline

  Extension

  	
   

  	
  Estimated

  Budget

  Adjustment

  	
   

  	
  Notes

  	
   

  
	
  ASSUMPTIONS

  	
   

  
	
  Scope Assumptions

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Sites

  	
   

  	
  500

  	
   

  	
   

  	
   

  	
  455

  	
   

  	
   

  	
   

  	
  (45

  	
  )

  	
  IRS Approved Site is basis For site management,
  Physician funnel assumptions are that 375 sites will become Active with -250
  becoming Active Enrolling.

  	
   

  
	
  Patients

  	
   

  	
  5,000

  	
   

  	
   

  	
   

  	
  2,000

  	
   

  	
   

  	
   

  	
  (3,000

  	
  )

  	
   

  	
   

  
	
  Timeline
  Assumptions

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Timeline
  Assumptions Total Months

  	
   

  	
  24.0

  	
   

  	
   

  	
   

  	
  31.0

  	
   

  	
  7

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  BUDGET

  

  DIRECT COSTS

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Clinical

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Project
  Management

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  New Scope 2006 includes maintenance of PM at 0.50 FTE
  through completion of enrollment (May-06), then reduction to 0.40 FTE through
  Oct-06. Timeline Extension includes the PM at a 0.40 FTE level for an
  additional 7.0 months before closeout (Nov-06 through May-07).

  	
   

  
	
  Project Setup

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Staff Training

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Site Management
  and Support

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  New Scope Q1 2005 adjusted per decision not to
  collect AEs. New Scope Q42005/2006 includes maintenance of CRA team at 5.0
  FTEs Aug-05 through Dec-05 vs. 2.5 FTEs in Revision #2 budget (Reliant
  Request, then reduction of CRA staff from 2.5 FTEs to 2.0 FTEs from Jan-06
  through Oct-06 (lower site/patient counts. Timeline Extension includes 2.0
  CRA FTEs for 7.0 additional Moths before closeout (Nov-06 through May-07). 

  	
   

  
	
  Regulatory
  Document and File Management

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  New Scope reflects reduction in number of site files
  created/maintained. Timeline Extension includes 0.29 FTEs for 7.0 additional
  months before closeout (Nov-06 through May-07).

  	
   

  
	
  TOTAL 

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Information
  Systems

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  PPD DirectConnect
  Setup

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  PPD DirectConnect
  Maintenance

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  ClinTrack Setup

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  ClinTrack
  Maintenance

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  TOTAL

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Data
  Management

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Adverse event coding removed from budget

  	
   

  
	
  Setup Database

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Maintain Database

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Total Document Management

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Data Review and
  Clean-Up

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Import External
  Data

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Transter Database

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Project
  Management

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  TOTAL

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
																							







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


3

















 


Modification
Number 2


 


	
  Electronic
  Data Capture

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  New scope Q1
  2005 adjusted for removal of AE collection

  	
   

  
	
  EDC Requirements

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Database
  Requirements

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Forms Control
  Implementation

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Data Transfer
  Functionality

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Site Initiation
  and Training

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Help Desk Support

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Protect
  Management

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  System
  Maintenance

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Impart External
  Data

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Ongoing Project
  Maintenance

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  CRF Revisions

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
   

  	
   

  	
   

  	
   

  
	
  Investigator
  Meeting

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  SAE Changes to
  EDC System

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  TOTAL

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Health Outcomes

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Monthly
  Maintenance

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Tables, Listing
  and Figures

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  SAP Text and TLF
  Shells

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Final CSR Text

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Survey Program

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Personalized
  Reports

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  TOTAL

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  TOTAL DIRECT
  COSTS

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  TOTAL
  NEW DIRECT COST BUDGET

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  ESTIMATED
  PASS-THROUGH COSTS

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

   

  	
  New Est. 

  Totals

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  1RB Reimbursement

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Clinical Grants

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  Projected based on 2,000 patients completing 12
  months of follow-up

  	
   

  
	
  Phone/Fax

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Study Kits

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  Based on actual spent

  	
   

  
	
  Postage

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Investigators’
  Meeting

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Physican Training
  Webcast

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  Based on actual spent

  	
   

  
	
  TOTAL
  PASS-THROUGH COSTS

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  TOTAL
  NEW EST INDIRECT COST BUDGET

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  ORIGINAL
  CONTRACT VALUE

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  CONM11002 VALUE

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  TOTAL ESTIMATED
  BUDGET ADJUSTMENT

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


4

















 


Modification Number 1


EXHIBIT B —
PAYMENT SCHEDULE


Direct
Costs:


 


	
   

  	
   

  	
  Amount

  	
   

  	
  Date

  	
   

  	
  Invoiced/Not Yet Paid

  	
   

  
	
  Execution
  of contract

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Execution
  of contract modification #1

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  4/25/2005

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Monthly:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Monthly Project
  Mgmt Fee of $[* * *] for 14 Months

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  4/25/05 - 4/24/06

  	
   

  	
   

  	
   

  
	
  February 2005 - March 2006

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Monthly Project
  Mgmt Fee of $[* * *] for April for 14 Months

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $[* * *] (April 06

  	
  )

  	
  $ [* * *] (May 06

  	
  )

  
	
  2006 - May 2007

  	
   

  	
   

  	
   

  	
  Paid 6/6/06

  	
   

  	
  Invoiced 5/31/06

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Milestones:*

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Clinical:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  First Site
  Initiated

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  6/21/2005

  	
   

  	
   

  	
   

  
	
  Last Site
  Initialed

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  11/29/2005

  	
   

  	
   

  	
   

  
	
  First Patient
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  7/12/2005

  	
   

  	
   

  	
   

  
	
  25% Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  11/29/2005

  	
   

  	
   

  	
   

  
	
  50% Patients Enrolled

  	
   

  	
   

  	
  [* * *]

  	
   

  	
  1/17/2006

  	
   

  	
   

  	
   

  
	
  75% Patients Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
  5/22/2006

  	
   

  
	
  All Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
   

  	
   

  
	
  Sites Closed-out

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
   

  	
   

  
	
  Final Study
  Report Delivered

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Data
  Management:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Database Set-up 

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  8/1/2005

  	
   

  	
   

  	
   

  
	
  50% CRF entered 

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
   

  	
   

  
	
  100% CAF entered

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
   

  	
   

  
	
  Database Lock

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Biostatistics:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Draft Analysis
  Plan 

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  12/27/2005

  	
   

  	
   

  	
   

  
	
  Final Analysis
  Plan

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
   

  	
   

  
	
  Draft Tables
  & Listings

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
   

  	
   

  
	
  Final Tables
  & Listings

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  —

  	
   

  	
   

  	
   

  
	
  Total Direct
  Costs

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Direct
  Cost Paid by Sponsor to PPD as of 5/31/06

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining
  Direct Cost to be Paid

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
												



 


Estimated Pass Through Costs:


 


	
   

  	
   

  	
  Contract Estimates

  	
   

  	
  Paid Out by PPD

  	
   

  
	
  Pass
  Throughs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Investigator
  Meeting

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  IRB Fees /
  Clinical Grants**

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Physician
  Training/WebCasts

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Recruitment/Advertisement
  (Study Kits)

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Phone/Fax

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Postage

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total
  Estimated Pass Through Costs

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Pass
  Throughs Paid by Sponsor to PPD as of 5/31/06

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining
  Quarterly Estimates (to be invoiced at the beginning of each quarter)

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Q3 2006

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Q4 2006

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Q1 2007

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Q2 2007

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Q3 2007

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Q4
  20137

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Total
  Remaining indirect Cost to be Paid by Sponsor***

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Project Grand
  Total

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total Paid as of
  5/31/06

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  RemainingCost to
  be Paid (As of May 31, 2006)

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  







*                                                   In the event that the
study delayed or put on hold for a period of greater than 30 days, PPD will
invoice sponsor on a pro-rated basis for all milestones that are partially completed.


**                                            PPD will not release
payment for investigator grants until sponsor has remitted the applicable
amount.


***                                     Remaining pass through cost will be billed
quarterly based on latest projections beginning July 2006.


 


[* *
*]:                    Certain
information on this page has been omitted and filed separately with the
Commission.  Confidential treatment has
been requested with respect to the omitted portions.


 


5










 


Contract Modification to Project
Addendum Dated 31 January 2005


 


	
  Effective Date:

  	
  May 1, 2007

  	
   

  	
  Sponsor:

  	
  Reliant Pharmaceuticals,

  Inc.

  
	
  Protocol Name:

  	
  Atrial Fibrillation: Focus

  	
   

  	
  Sponsor 

  	
  Saishree Ramalingam, MS

  
	
   

  	
  on Effective Clinical

  	
   

  	
  Contact:

  	
  Senior Clinical Project

  
	
   

  	
  Treatment Strategies

  	
   

  	
   

  	
  Manager, Research &

  
	
   

  	
  (AFFECTS) Registry

  	
   

  	
   

  	
  Development

  
	
  PPD Project

  	
   

  	
   

  	
  Sponsor Contact

  	
   

  
	
  Manager:

  	
  Todd Nelson

  	
   

  	
  Telephone No:

  	
  908-860-7017

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Bus Dev

  	
   

  	
   

  	
  Sponsor Contact

  	
   

  
	
  Director:

  	
  Dominic Mancini

  	
   

  	
  Fax No:

  	
  908-542-4460

  



 


The Project Addendum by and between PPD Development, LP (“PPD”) and
Reliant Pharmaceuticals, Inc. (“Reliant”) effective January 31, 2005, regarding
the above referenced Protocol shall be modified as set forth below:


 


Description of Contract Modification to Project Addendum: Modifications
to Clinical, Biostatistics, Data Management and Medical Writing include:


 


Clinical Modifications


 


Direct Costs:


•          CRA hours were added to account for
changes in the Central IRB (CIRB) requirement of an annual review at the site
level, as well as a significant increase in query management activity (e.g.,
the average number of queries per patient is now seven vs. the originally
proposed two).


•          CRA hours budgeted to manage Local IRB
renewals were decreased due to the decrease in the number of local IRB sites
that required an annual review.


•          CRA hours budgeted to the clinical review
of CRF pages were decreased to reflect the decrease in enrolled patients from
2,000 (ConMod1) to 1,535 (final figure).


•          Research Assistant time was added to
provide administrative support for the increased CIRB requirements while CSS
hours were removed from the budget.


•          Document Technician and Records
Specialist hours budgeted for physician file management were decreased to
reflect the decrease in IRB-approved sites from 500 to 455.


 


Indirect
Costs:


•          Estimated Clinical Grant reduction of $[*
* *] based on:


•          Decrease due to reduced number of
enrolled patients from 2,000 to 1,535; ((2.000 - 1,535 pts.) x $[* * *] pt. = $[*
* *]).


•          Additional decrease due to number of
patients that completed the study (i.e., patient disposition form completed)
but did not complete all visits (2,000 ND visits x $[* * *] / visit = $[* * *]).






[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


1

















 


 


Health Outcomes/Biostatistics Modifications


 


•          PPD’s Health Outcomes/Biostatistics team
has removed costs from budget for writing the Clinical Study Report (CSR). This
task has been moved to the Medical Writing Section of the budget.


•          Statistical table and listing counts for
final analysis increased from the originally contracted 30 tables and 2 listings
to 50 tables and 16 listings.


•          Statistical table counts for interim
analysis increased from originally contracted 6 to 23.


•          Based upon discussions at the data review
meeting in November 2006, three more tables were added for interim and final analyses.


•          Budget for physician reports has been
removed from PPD Health Outcomes/Biostatistics.


 


PPD GlobalView/Data Management Modifications


 


•          Additional queries outside the scope of
the existing contract were added to the GlobalView (EDC) system. These additional
queries necessitated updates to the Requirements Document (RD). Each query
required coding and independent validation by the development team.


•          Enhancements to the Inclusion / Exclusion
eCRF on the GlobalView website were requested. These enhancements necessitated
updates to the RD as well as coding by the development team and validation of
all changes.


•          Addition of a “Not Done” checkbox to each
eCRF visit form within the EDC system was requested, which required updates to
the RD, coding by the development team and validation of all changes.


 


Medical Writing Modifications


 


•          PPD’s Medical Writing team will write a
Clinical Study Report (CSR) for this study, in accordance with Reliant
specifications and current ICH Guidelines. PPD will prepare the CSR using the
PPD report template.


•          The increased cost for writing the CSR is
reflective of the increased clinical and biostatistical scope in this registry
along with the Reliant request that ICH Guidelines be utilized. The increased
number of Tables and Listings for the final and interim analyses adds to the
length / complexity as well as the clinical quality assurance and technical
review requirements of the draft and final report.


•          The personalized physician reports have
been removed from the budget. Two registry summary reports are included; the
interim report has already been delivered and the final report will be
delivered at the end of the study.


 


A detailed explanation of costs has been developed in an Excel
spreadsheet (Reliant AFFECTS Program: Budget Review) is attached hereto as
Exhibit A. Payment of such costs shall be made in accordance with the Revised
Payment Schedule attached hereto as Exhibit B.


 


Upon execution by the parties. this Contract Modification will be made
a part of the Project Addendum and incorporated by reference therein. Except as
expressly provided herein or in any other mutual written agreement by the
parties, all terms and conditions contained in the Project Addendum shall
remain in full force and effect. All capitalized terms used but not otherwise
defined herein shall have the meanings ascribed to them in the Project
Addendum.


 


2

















 


ACCEPTED AND AGREED:


 


	
  PPD Development, LP

  	
   

  	
  Reliant Pharmaceuticals, Inc.

  
	
  By: PPD GP, LLC

  	
   

  	
   

  
	
  Its General Partner

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ C. Randall Marchbanks

  	
   

  	
  By:

  	
  /s/ Steve Ketchum

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name:

  	
  C. Randall Marchbanks, Pharm.D.

  	
   

  	
  Name:

  	
  Steve Ketchum, Ph.D.

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  Vice President, Business Development PPD

  	
   

  	
  Title:

  	
  Sr. VP, R&D and Medical Affairs

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  [SEAL]

  	
   

  	
   

  	
  [SEAL]

  



 


3

















 


EXHIBIT A — BUDGET REVIEW


 


	
  Budget

  	
   

  	
  Contract

  Value

  	
   

  	
  CM # 1

  Changes

  	
   

  	
  Contract

  Value + CM

  #1 Changes

  	
   

  	
  CM #2 Changes

  (excluding CSR

  and Physician

  Report Changes)

  	
   

  	
  CSR

  Changes

  	
   

  	
  Physician

  Report

  Changes

  	
   

  	
  New Total

  Contract

  Value

  	
   

  	
  Delta

  	
   

  
	
  Direct
  Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Clinical

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Information
  Systems

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Data Management

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Electronic Data
  Capture

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Health Outcomes

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Medical Writing

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Physician
  Reports Support

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Total
  Direct

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Indirect
  Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  IRB
  Reimbursement

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Clinical Grants

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Phone/Fax

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Study Kits

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Postage

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Investigators’
  Meeting

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Physician
  Training Webcast

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Total
  Indirect

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  TOTAL
  VALUE

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


4

















 


EXHIBIT B — PAYMENT SCHEDULE


 


	
  Direct Costs

  	
   

  	
  Amount

  	
   

  	
  Date Paid

  	
   

  	
  Invoiced/

  Not Yet Paid

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Execution
  of contract

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  04/25/2005

  	
   

  	
   

  	
   

  
	
  Execution
  of contract modification #1

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  08/21/2006

  	
   

  	
   

  	
   

  
	
  Execution
  of contract modification #2

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Monthly:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Monthly Project
  Mgmt Fee of $[* * *] for 14 Months

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  4/25/05 - 4/24/06

  	
   

  	
   

  	
   

  
	
  February 2005 -
  March 2006

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Monthly Project
  Mgmt Fee of $[* * *] for 14 Months

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  04/06 — 02/07 Paid as
  of 4/17/07

  	
   

  	
  $

  	
  [* * *] (03/07 PM Fee)
  Invoiced 3/29/07

  	
   

  
	
  April 2006 - May
  2007

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Milestones:*

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Clinical:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  First Site
  Initiated

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  06/21/2005

  	
   

  	
   

  	
   

  
	
  Last Site
  Initiated

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  11/29/2005

  	
   

  	
   

  	
   

  
	
  First Patient
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  07/12/2005

  	
   

  	
   

  	
   

  
	
  25% Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  11/29/2005

  	
   

  	
   

  	
   

  
	
  50% Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  01/17/2006

  	
   

  	
   

  	
   

  
	
  75% Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  06/19/2006

  	
   

  	
   

  	
   

  
	
  All Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  All Sites
  Closed-out

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Study
  Report Delivered

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Data
  Management:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Database Set-up

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  08/01/2005

  	
   

  	
   

  	
   

  
	
  50% CRF entered

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  08/02/2006

  	
   

  	
   

  	
   

  
	
  100% CRF entered

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Database Lock

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Biostatistics:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Draft Analysis
  Plan

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  12/27/2005

  	
   

  	
   

  	
   

  
	
  Final Analysis
  Plan

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  03/06/2007

  	
   

  	
   

  	
   

  
	
  Draft Tables
  & Listings

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Tables
  & Listings

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
										







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


5

















 


	
  Total
  Direct Costs

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Direct
  Cost Paid by Sponsor to PPD as of 4/17/07

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining
  Direct Cost to be Paid

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Estimated
  Pass Through Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Pass
  Throughs:

  	
   

  	
   

  	
   

  	
  Pass
  Throughs Paid by PPD

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Investigator
  Meeting

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Clinical
  Grants/IRB Fees

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Physician
  Training/Webcasts

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Recruitment/Advertisement
  (Study Kits)

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Phone/Fax

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Postage

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total
  Estimated Pass Through Costs* * *

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Pass
  Throughs Paid by Sponsor to PPD as of 4/17/07

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining Quarterly estimates

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Q3 2006

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  08/08/2006

  	
   

  	
   

  	
   

  
	
  Q4 2006

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  11/13/2006

  	
   

  	
   

  	
   

  
	
  Q1 2007

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  02/28/2007

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining
  Indirect Cost to be Paid by Sponsor* * **

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Project
  Grand Total

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total
  Paid as of 4/17/07

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining
  Cost to be Paid (As of April 17, 2007)

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  



 






* In the event that the study is delayed or put on hold for a period of
greater than 30 days, PPD will invoice sponsor on a pro-rated basis for all
milestones that are partially completed.


** PPD will not release payment for investigator grants until sponsor
has remitted the applicable amount.


*** If total pass through expenses exceed $[* * *] the cost will be
invoiced to the Sponsor as vendor invoices are received.


* * ** Remaining pass through cost will be billed quarterly based on
latest projections beginning July 2006. Pending Sponsor approval, overpaid pass
through cost will be applied against Execution of CM2 invoice.


 


[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


6














 


Contract Modification to Project
Addendum Dated 31 January 2005


 


	
  Effective Date:

  	
  August 09, 2007

  	
  Sponsor:

  	
  Reliant Pharmaceuticals,

  Inc.

  
	
  Protocol Name:

  	
  Atrial Fibrillation: Focus

  	
  Sponsor

  	
  Saishree Ramalingam. MS

  
	
   

  	
  on Effective Clinical

  	
  Contact:

  	
  Senior Clinical Project

  
	
   

  	
  Treatment Strategies

  	
   

  	
  Manager, Research &

  
	
   

  	
  (AFFECTS) Registry

  	
   

  	
  Development

  
	
  PPD Project

  	
   

  	
  Sponsor Contact

  	
   

  
	
  Manager:

  	
  Todd Nelson

  	
  Telephone No:

  	
  908-860-7017

  
	
   

  	
   

  	
   

  	
   

  
	
  Bus Dev

  	
   

  	
  Sponsor Contact

  	
   

  
	
  Director:

  	
  Dominic Mancini

  	
  Fax No:

  	
  908-542-4460

  



 


The Project Addendum by and between PPD Development, LP (“PPD”) and
Reliant Pharmaceuticals, Inc. (“Reliant”) effective January 31, 2005, regarding
the above referenced Protocol shall be modified as set forth below:


 


Description of Contract Modification to Project Addendum: Modifications
to Biostatistics and Data Management include:


 


Health Outcomes/Biostatistics Modifications


 


Task 1: Add four univariate analyses in support of Tables 9.2.2, 9.3,
9.4, and 10 before finalizing the multivariate analyses. These univariate
analyses will be provided on 08/13/07 and will be discussed with the sponsor
for clinical inputs prior to completing the multivariate analyses. These will
be provided as SAS output files and will be titled “Univariate Analysis in
support of Table [x]”, one SAS output for each table of multivariate model.
Cost for these analyses is $[* * *], which is broken down by
position, as detailed below:


•            Biostatistician - $[* * *]


•            Programmer Analyst - $[* * *]


•            Sr. Programmer Analyst - $[* * *]


•            Associated Director of Programming - $[* * *]


•            Director of Biostatistics - $[* * *]


•            Manager of Quality Review - $[* * *]


 


Task 2: Add three additional tables, two unique (12.1.6 and 7.4), one
repeat (6A). All are part of final TL set, scheduled for 08/13/07 delivery.
Cost for this task is $[* * *], which is broken down by position, as
detailed below:


•            Biostatistician - $[* * *]


•            Programmer Analyst - $[* * *]


•            Sr. Programmer Analyst - $[* * *]


•            Associated Director of Programming - $[* * *]


•            Director of Biostatistics - $[* * *]


•            Manager of Quality Review - $[* * *]






[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


1

















 


Task 3: Add four additional data Review Listings (Medical History
unique event: Body system category; Non-AF Medication Log unique ‘indication’:
ECG tests with abnormal and clinically significant results; Patient level
Medical History and baseline test) that were incorporated in the SAP in January
2007, approved 05/31/07 as part of the SAP, delivered 07/09/07. Coded
spreadsheets from Reliant were converted to SAS data and incorporated into the
analysis datasets for draft tables, which will be delivered on 08113/2007.
These will be redelivered after the Data Review Meeting if needed. Cost for
this task is $[* * *], which is broken down by position, as detailed
below:


•            Biostatistician - $[* * *]


•            Programmer Analyst - $[* * *]


•            Sr. Programmer Analyst - $[* * *]


•            Associated Director of Programming - $[* * *]


•            Director of Biostatistics -
$[* * *]


•            Manager of Quality Review -
$[* * *]


 


Task 4: Add five data listings with indicated delivery dates:


(1)    More than one AAD started on the same day (12/13106),


(2)    Fatal SAE or SAE with death outcome (12/13/06),


(3)    List of Multiple Antiarrhythmic Drugs that were taken
by a patient from Enrollment through first 30 days after enrolled (01/02/07),


(4)    Patients with abnormal and clinically significant
tests at baseline (02/19/07), and


(5)    Patients with lone AF or AF with hypertension and age
< 60 years old & Summary of frequency - Number of Patients with lone AF
or AF with hypertension and age < 60 years old (02/19/07).


 


Cost for this task is $[* * *], which is broken down by
position, as detailed below:


•    Biostatistician - $[* * *]


•    Programmer Analyst - $[* * *]


•    Sr. Programmer Analyst - $[* * *]


•    Associated Director of Programming - $[* * *]


•    Director of Biostatistics - $[* * *]


•    Manager of Quality Review -
$[* * *]


 


Task 5: Added additional ad hoc SAE listing (Serious Adverse Events of
Patients who did not receive investigator approval). Delivery date will be
after 08/13/07. PPD lead statistician will send a listing shell for Reliant’s
review/approval before the team starts programming for the actual listing. Cost
for this ad hoc statistical listing is $[* * *], which is broken down
by position, as detailed below:


•    Biostatistician - $[* * *]


•    Programmer Analyst - $[* * *]


•    Sr. Programmer Analyst - $[* * *]


•    Associated Director of Programming -
$[* * *]


•    Director of Biostatistics -
$[* * *]


•    Manager of Quality Review -
$[* * *]






[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


2

















 


PPD GlobalView/Data Management Modifications


 


Data Transfer of AFF_DEMOG and AFF_INCEXL Datasets for patients: US0084-0007,
US0084- 009, US0084-0010 and US0084-0013. Cost for this data transfer is [* * *],
which is broken down by position as detailed below:


•    Programming Manager - $[* * *]


•    SAS Programmer - $[* * *]


•    Associate Project Manager - $[* * *]


 


ACCEPTED AND AGREED:


	
  PPD Development, LP

  	
   

  	
  Reliant Pharmaceuticals, Inc.

  
	
  By: PPD GP, LLC

  	
   

  	
   

  
	
  Its General Partner

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Brent K. Conway

  	
   

  	
  By:

  	
  /s/ Roderick Carter

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name:

  	
  Brent K. Conway

  	
   

  	
  Name:

  	
  Roderick Carter

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  VP Operations Finance

  	
   

  	
  Title:

  	
  VP, Research & Development

  







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


3

















 


EXHIBIT A- BUDGET REVIEW


 


	
  Budget

  	
   

  	
  Contract

  Value

  	
   

  	
  CM #1

  Changes

  	
   

  	
  Contract

  Value + CM

  #1 Changes

  	
   

  	
  CM #2
  Changes

  (excluding CSR

  and Physician

  Report Changes)

  	
   

  	
  CSR

  Changes

  	
   

  	
  Physician

  Reports

  Changes

  	
   

  	
  CM #3

  Changes

  	
   

  	
  New
  Total

  Contract

  Value

  	
   

  	
  Delta†

  	
   

  
	
  Direct
  Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Clinical

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Information
  Systems

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Data Management

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Electronic Data
  Capture

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Biostatistics/Flealth
  Outcomes

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Medical Writing

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Physician
  Reports Support

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Total
  Direct

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Indirect
  Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  IRB
  Reimbursement

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Clinical Grants

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Phone/Fax

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Study Kits

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Postage

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Investigators’
  Meeting

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Physician
  Training Webcast

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
  Total
  Indirect

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  TOTAL
  VALUE

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


4

















 


EXHIBIT B - PAYMENT SCHEDULE


Direct Costs:


	
   

  	
   

  	
  Amount

  	
   

  	
  Date Paid

  	
   

  	
  Invoiced/Not Yet Paid

  	
   

  
	
  Execution
  of contract

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  04/25/2005

  	
   

  	
   

  	
   

  
	
  Execution
  of contract modification #1

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  08/21/2006

  	
   

  	
   

  	
   

  
	
  Execution
  of contract modification #2

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  06/19/2007

  	
   

  	
   

  	
   

  
	
  Execution
  of contract modification #3

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Monthly:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Monthly Project
  Mgnt Fee of $[* * *] for 14 Months

  February 2005 - March 2006

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  4/25/05 - 4/24/06

  	
   

  	
   

  	
   

  
	
  Monthly Project
  Mgnit Fee of $[* * *] for 14 Months

  April 2006 - May 2007

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  April 2006 - March 2007,
  May 2007 Paid as of 8/8/07

  	
   

  	
  $

  	
  [* * *] (4/07 PM Fee)
  Invoiced 4/30/07

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Milestones:*

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Clinical:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  First Site
  Initiated

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  06/21/2005

  	
   

  	
   

  	
   

  
	
  Last Site
  Initiated

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  11/29/2005

  	
   

  	
   

  	
   

  
	
  First Patient
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  07/12/2005

  	
   

  	
   

  	
   

  
	
  25% Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  11/29/2005

  	
   

  	
   

  	
   

  
	
  50% Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  01/17/2006

  	
   

  	
   

  	
   

  
	
  75% Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  06/19/2006

  	
   

  	
   

  	
   

  
	
  All Patients
  Enrolled

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  06/19/2007

  	
   

  	
   

  	
   

  
	
  All Sites
  Closed-out

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Study
  Report Delivered

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Data
  Management:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Database Set-up

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  08/01/2005

  	
   

  	
   

  	
   

  
	
  50% CRF entered

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  08/02/2006

  	
   

  	
   

  	
   

  
	
  100% CRF entered

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  08/06/2007

  	
   

  	
   

  	
   

  
	
  Database Lock

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Biostatistics:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Draft Analysis
  Plan

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  12/27/2005

  	
   

  	
   

  	
   

  
										







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


5

















 


	
  Final Analysis
  Plan

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  03/06/2007

  	
   

  	
   

  	
   

  
	
  Draft Tables
  & Listings

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Tables
  & Listings

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total Direct
  Costs

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Direct Cost Paid
  by Sponsor to PPD as of 8/8/07

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining
  Direct Cost to be Paid

  	
   

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Estimated
  Pass Through Costs:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Pass
  Throughs

  	
   

  	
   

  	
   

  	
  Pass
  Throughs

  Paid by PPD

  	
   

  	
   

  	
   

  
	
  Investigator Meeting

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Clinical
  Grants/IRS Fees

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Physician
  Training/Webcasts

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Recruitment/Advertisement
  (Study Kits)

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Phone/Fax

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
  Postage

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total
  Estimated Pass Through Costs

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Pass
  Throughs Paid by Sponsor to PPD as of 8/8/07***

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining
  Quarterly estimates

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Q3 2006

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  08/08/2006

  	
   

  	
   

  	
   

  
	
  Q4 2006

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  11/13/2006

  	
   

  	
   

  	
   

  
	
  QI 2007

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
  02/28/2007

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining
  Indirect Cost to be Paid by Sponsor***

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Project
  Grand Total

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total
  Paid as of 8/8/07

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Remaining
  Cost to be Paid

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  (As of
  August 8, 2007)

  	
   

  	
  $

  	
  [* * *]

  	
   

  	
   

  	
   

  	
   

  	
   

  



 






* In the event that the study is delayed or put on hold for a period of
greater than 30 days, PPD will invoice sponsor on a pro-rated basis for all
milestones that are


partially completed.


**PPD will not release payment for investigator grants until sponsor
has remitted the applicable amount.


 


[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


6

















 


*** If total pass through expenses exceed $[* * *] the cost will be
invoiced to the Sponsor as vendor invoices are received.


****Remaining pass through cost will be billed quarterly based on
latest projections beginning July 2006. Pending Sponsor approval, overpaid pass
through cost- will be applied against Execution of CM2 invoice.


 


[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


7














Modification Number
4


Contract Modification to
Project Addendum Dated 31 January 2005


 


	
  Effective
  Date:

  	
  September 14, 2007

  	
   

  	
  Sponsor:

  	
  Reliant
  Pharmaceuticals, Inc.

  
	
  Protocol
  Name:

  	
  Atrial Fibrillation:
  Focus

  	
   

  	
  Sponsor
  Contact:

  	
  Saishree Ramalingam, MS

  
	
   

  	
  on Effective
  Clinical

  	
   

  	
   

  	
  Senior Clinical
  Project

  
	
   

  	
  Treatment
  Strategies

  	
   

  	
   

  	
  Manager,
  Research &

  
	
   

  	
  (AFFECTS)
  Registry

  	
   

  	
   

  	
  Development

  
	
  PPD
  Project

  	
   

  	
   

  	
  Sponsor
  Contact

  	
   

  
	
  Manager:

  	
  Todd Nelson

  	
   

  	
  Telephone
  No:

  	
  908-860-7017

  
	
  Bus
  Dev

  	
   

  	
   

  	
  Sponsor
  Contact

  	
   

  
	
  Director:

  	
  Dominic Mancini

  	
   

  	
  Fax No:

  	
  908-542-4460

  



The Project Addendum by and between PPD Development, LP (“PPD”) and
Reliant Pharmaceuticals, Inc. (“Reliant”) effective January 31, 2005,
regarding the above referenced Protocol shall be modified as set forth below:


Description of Contract
Modification to Project Addendum: Modifications to Biostatistics include:


Health
Outcomes/Biostatistics Modifications


Task 1: One
additional listing for protocol violation: this statistical listing will be
numbered as Listing 6; following columns will
be included in the listing: patient ID #, reasons of protocol violations – structure heart disease, coronary
artery disease, congestive heart failure, hypertension, and medical history terms, test results, and terms of
indication of non-AF medication associated with reason of protocol
violation; data from the client data review listings #1 – Medical History and
Abnormal/Clinical Significant Test at Baseline, and #3 – Indication of Non-AF Medications. The cost for this additional
listing is $[* * *], which is broken down by position, as
detailed below:


·                             Biostatistician – $[* * *]


·                             Programmer Analyst - $[* * *]


·                             Sr. Programmer Analyst - $[* * *]


·                             Associated
Director of Programming – $[* * *]


·                             Director
of Biostatistics - $[* * *]


·                             Manager
of Quality Review – $[* * *]


Task 2: Three additional repeated tables as
following:


·                             Table
8.7.2 Antiarrhythmic Drug Prescription Patterns for Cardioversion (Per
Protocol)


·                             Table
8.7.2A Antiarrhythmic Drug Prescription Patterns for Cardioversion (All
Enrolled)


·                             Table
9.2.3 Poisson Regression Analysis of Rate of Validated AF Recurrence in One
Year Follow-up






[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


1

















 


The cost for these
additional tables is $[* * *],
which is broken down by position, as detailed below:


·                             Biostatistician – $[* * *]


·                             Programmer Analyst - $[* * *]


·                             Sr. Programmer Analyst - $[* * *]


·                             Associated
Director of Programming – $[* * *]


·                             Director
of Biostatistics – $[* * *]


·                             Manager
of Quality Review – $[* * *]


 




	
  ACCEPTED
  AND AGREED:

  	
   

  	
   

  	
  Reliant
  Pharmaceuticals, Inc.

  
	
  PPD
  Development, LP

  By: PPD GP, LLC

  Its General Partner

  	
   

  	
   

  	
   

  
	
  By: 

  	
  

  /s/ C.Randall
  Marchbanks

  	
   

  	
  By: 

  	
  

  /s/ R.N. Carter

  
	
  Name: 

  	
  C.Randall Marchbanks,
  Pharm.D.

  	
   

  	
  Name: 

  	
  R.N. CARTER

  
	
  Title: 

  	
  Vice President, Business Development PPD

  	
   

  	
  Title: 

  	
  VP CLINICAL

  
	
   

  	
  19 Sept 2007

  	
   

  	
   

  	
  09/21/2007

  
	
   

  	
  [SEAL]

  	
   

  	
   

  	
   

  










[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


2

















 


Modification Number 4


EXHIBIT A- BUDGET REVIEW


 


	
  Budget

  	
   

  	
  Contract

  Value

  	
   

  	
  CM
  #1

  Changes

  	
   

  	
  Contract Value

  + CM #1

  Changes

  	
   

  	
  CM #2
  Changes

  (excluding CSR

  and Physician

  Report Changes)

  	
   

  	
  CSR

  Changes

  	
   

  	
  Physician

  Reports

  Changes

  	
   

  	
  CM
  #3

  Changes

  	
   

  	
  CM
  #4

  Changes

  	
   

  	
  New
  Total

  Contract

  Value

  	
   

  
	
  Direct
  Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Clinical

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Information Systems

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Data Management

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Electronic Data
  Capture

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Biostatistics/Health
  Outcomes

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Medical Writing

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Physician Reports Support

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Total
  Direct

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Indirect
  Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  IRB Reimbursement

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Clinical Grants

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Phone/Fax

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Study Kits

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Postage

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Investigators’
  Meeting

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Physician
  Training Webcast

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
  Total
  Indirect

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  TOTAL
  VALUE

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  	
  $[* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  







[* * *]:       Certain information on this page has been
omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


3

















Modification Number 4


 


EXHIBIT B – PAYMENT SCHEDULE


 


	
  Direct Costs:

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Amount

  	
  Date Paid

  
	
  Execution
  of contract

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  04/25/2005

  
	
  Execution
  of contract modification #1

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  08/21/2006

  
	
  Execution
  of contract modification #2

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  06/19/2007

  
	
  Execution
  of contract modification #3

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  Invoiced

  
	
  Monthly:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Monthly Project Mgmt
  Fee of

  	
         $[* * *]

  	
  for

  	
  14

  	
  Months

  	
   

  	
  $

  	
  [* * *]

  	
  4/25/05 - 4/24/06

  
	
   

  	
   

  	
  February 2005 - March 2006

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Monthly Project Mgmt
  Fee of

  	
         $[* * *]

  	
  for

  	
  14

  	
  Months

  	
   

  	
  $

  	
  [* * *]

  	
  6/6/06 - 8/20/07

  
	
   

  	
   

  	
  April 2006 - May 2007

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Milestones:*

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Clinical:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  First Site Initiated

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  06/21/2005

  
	
   

  	
  Last Site Initiated

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  11/29/2005

  
	
   

  	
  First Patient Enrolled

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  07/12/2005

  
	
   

  	
  25% Patients Enrolled

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  11/29/2005

  
	
   

  	
  50% Patients Enrolled

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  01/17/2006

  
	
   

  	
  75% Patients Enrolled

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  06/19/2006

  
	
   

  	
  All Patients Enrolled

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  06/19/2007

  
	
   

  	
  All Sites Closed-out

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  Invoiced

  
	
   

  	
  Final Study Report
  Delivered

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
  Data Management:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Database Set-up

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  08/01/2005

  
	
   

  	
  50% CRF entered

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  08/02/2006

  
	
   

  	
  100% CRF entered

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  08/06/2007

  
	
   

  	
  Database Lock

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
  Biostatistics:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Draft Analysis Plan

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  12/27/2005

  
	
   

  	
  Final Analysis Plan 

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *] 

  	
  03/06/2007

  







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


4

















 


Modification Number 4


 


	
   

  	
  Draft Tables & Listings

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  Invoiced

  
	
   

  	
  Final Tables & Listings

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
  Total Direct Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
  Direct Cost Paid by
  Sponsor to PPD as of 9/7/07

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Remaining
  Direct Cost to be Paid

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
   

  	
   

  







[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


 


5

















 


	
   

  	
  Estimated
  Pass Through Cost

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Pass
  Throughs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Pass Throughs

  Paid by PPD

  
	
   

  	
  Investigator Meeting

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  $[* * *]

  
	
   

  	
  Clinical Grants/IRB
  Fees

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  $[* * *]

  
	
   

  	
  Physician
  Training/Webcasts

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  $[* * *]

  
	
   

  	
  Recruitment/Advertisement
  (Study Kits)

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  $[* * *]

  
	
   

  	
  Phone/Fax

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  $[* * *]

  
	
   

  	
  Postage

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  $[* * *]

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Total Estimated Pass Through Costs
  **

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
  $[* * *]

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Pass Throughs Paid by Sponsor to PPD as of 9/7/07

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Remaining Indirect Cost to be Paid by Sponsor***

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Project Grand Total

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
  Total Paid as of 9/7/07

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  
	
   

  	
  Remaining Total Cost to be
  Paid (As of 9/7/07)

  	
   

  	
   

  	
   

  	
  $

  	
  [* * *]

  	
   

  



*In the event that the study is delayed or put on hold for a period of
greater than 30 days, PPD will invoice sponsor on a pro-rated basis for all
milestones that are partially completed.


** if total pass through expenses exceed $[* * *] the cost will be
invoiced to the Sponsor as vendor invoices are received. 


*** Overpayment of any pass through amounts will be reconciled arid
reimbursed at study end.






[* *
*]:       Certain information on this page
has been omitted and filed separately with the Commission.  Confidential treatment has been requested
with respect to the omitted portions.


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