Exhibit 10.2

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

 

 

 

LOGO [g77692ex10_1apg1.jpg]   LOGO [g77692ex10_1bpg1.jpg]   A Proposal to
Provide Clinical Research Services for:  

 

Protocol: BUP-201

 

*** Evaluation of the Efficacy, Safety, and Tolerability of BEMA™ Buprenorphine
in the Treatment of Pain Associated with ***

 

Prepared for:

David Blum, MD

Vice President, Clinical Research and Medical Affairs

BioDelivery Sciences International

801 Corporate Center Drive, Suite 210

Raleigh, NC 27607

 

Tel:        919.582.9050

Fax:        919.582.9051

Email:    dblum@bdsinternational.com

    

Project No. ***

09 February 2009

Previous: ***

       

Prepared by:

Pam Myrick

  Senior Associate II, Proposal Development      LOGO
[g77692ex10_1premierresearch.jpg]   BRUCE M. WAKEMAN   Vice President   U.S.,
Business Development

 

   Premier Research Group    TEL: 727.865.0803    322 Monte Cristo Blvd   
MOBILE: 727.244.9809    Tierra Verde, FL 33715   
EMAIL: bruce.wakeman@premier-research.com

 

 

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Table of Contents

 

•

  

EXECUTIVE SUMMARY

   1

•

  

PROJECT CONSIDERATIONS

   3

•

  

PROJECT RESPONSIBILITIES

   4

•

  

PROJECT OUTLINE

   5

•

  

PROJECT TIMELINE

   6

•

  

PROJECT TEAM DESIGN

   7      

BDSI/Premier Research Project Team Organizational Chart

   8      

Project Team Leadership

   9

•

  

PROJECT IMPLEMENTATION PLAN

   12      

Project Plan Development

   12      

Parallel Processing Approach™

   12      

Start-up Activities

   12      

Enrollment Plan

   13      

Communication

   13

•

  

PRICE SUMMARY

   15

•

  

DETAILED COST ESTIMATE

   16      

Notes on Pass-through Estimates

   19      

I.

  

Travel Costs

   22      

II.

  

Institutional Review Board (IRB) Fees

   22      

III.

  

Shipping

   22      

IV.

  

Miscellaneous

   22

•

  

CLINICAL RESEARCH CENTER INVESTIGATOR GRANT SUMMARY

   20

•

  

SERVICE DESCRIPTIONS

   21      

2. Project Management

   26      

3. Clinical Monitoring and Site Management

   27      

4. Biostatistics

   31      

5. Quality Assurance

   33

•

  

PAYMENT SCHEDULE

   39

 

CONFIDENTIAL

This document is provided with the understanding that the copyright and the
information contained herein remains the

property of Premier Research Group Limited. It shall be kept confidential and
used only by the company or person to whom

it is addressed, for no purpose other than assessing the merits of Premier
Research Group Limited.

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WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Executive Summary

Premier Research Group Limited (“Premier Research”) is pleased to present this
revised proposal in support of the BEMA™ Buprenorphine program in patients with
***. In response to your request, we have prepared the following proposal
outlining our strategy to successfully conduct this study. We look forward to
this opportunity to collaborate with the BDSI team and appreciate the study
information you have provided.

We have attempted to accurately respond to your needs in the proposal text and
cost estimate, and trust that the information in this document will be
informative and valuable as you determine your outsourcing needs. Where there
are outstanding issues or answers yet unknown, Premier Research has made related
assumptions.

In the pages that follow, we present compelling reasons why Premier Research is
the best choice for this project. Those reasons include:

Premier Research is recognized as an industry leader in clinical research for
acute and chronic pain, having managed more than 350 analgesia trials treating
more than 90,000 patients. We have conducted some of the largest and most
important drug trials in pain in multi-center trials around the world and at our
Research Centers in the United States.

Mr. Michael Kuss, Vice President, Clinical Research Centers, in particular, is
an expert in the field of analgesia research and as part of Premier Research’s
commitment to quality assurance, is offered in a supervisory capacity at no
charge to BDSI throughout the course of the study. Mr. Kuss is familiar with
many of the aspects involved in conducting successful pain studies and will
offer his scientific guidance and therapeutic expertise on critical success
factors crucial to the conduct of this program.

Together with our operational experts, the senior leadership at Premier Research
understands the challenges and nuances involved in pain studies and will be
available to support the project team as needed. Our experienced study team will
provide more efficient program execution, including the ability to predict and
overcome complex study issues in an expeditious manner and complete this study
within the timeline BDSI has requested.

 

•  

Experienced Staff Available to Meet Your Timelines

Our experienced study team will provide more efficient study execution,
including the ability to predict and overcome complex study issues in an
expeditious manner. We can provide a detailed staffing plan, including team
member credentials, which are unrivaled in the industry.

 

•  

Top-Down Commitment to Customer Satisfaction

We are small enough to provide appropriate levels of oversight to ensure that
projects are conducted in a timely and efficient manner, but large enough to
provide Sponsor with staffing and pricing considerations appropriate to a long
term relationship.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Sponsor:    BioDelivery Sciences International Study Medication:    BEMA™
Buprenorphine Protocol Number:    BUP-201 Protocol Title:    *** Evaluation of
the Efficacy, Safety, and Tolerability of BEMA™ Buprenorphine in the Treatment
of Pain Associated with *** Clinical Phase:    II Indication:    ***
Participating Regions:    North America Number of Subjects Enrolled/Complete:   
*** Number of Sites Participating:    *** Premier Research Services Requested:
   Clinical Trial Management, Biostatistics, Quality Assurance Total Estimated
Investigator Grant:    $*** Duration of CRO Services:    *** Total Estimated
Premier Research Fees:    $***

We hope that the information in this document demonstrates our capabilities in
this indication and conveys Premier Research’s commitment to becoming a true
partner with you in reaching and exceeding study goals. We enthusiastically
anticipate the prospect of conducting this important program for BDSI and look
forward to further discussions with you regarding the information we have
provided.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Project Considerations

Premier Research understands the important role that we will play in the conduct
of this study and looks forward to collaborating with BDSI to assure the study’s
success. In preparing this proposal, we have sought input from our in-house
operations and medical specialists on the design, study timeline and other
factors related to enrollment and investigator site selection. The following are
issues that Premier Research has identified for your consideration and that we
feel are important to the successful completion of the program. The below
comments are based on the original study synopsis date *** provided by BDSI to
Premier Research.

 

  •  

Premier Research would like to recommend a ***.

 

  •  

We would also like to suggest the use of ***. If no *** are to be evaluated, we
would recommend that *** also be used as the ***.

 

  •  

Premier Research would like to suggest the use of the ***.

 

  •  

Premier Research would recommend the use of a modified BOCF imputation procedure
instead of the currently proposed *** for the primary analysis.

We welcome the opportunity to discuss further the issues associated with this
trial and present our capabilities in person upon BDSI’s request. Please see the
following project responsibilities, outline, timeline, and budget summary for a
complete list of assumptions and specifications that factored into our proposal.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Project Responsibilities

***

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Project Outline

***

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Project Timeline

 

Activity

 

Timeframe

 

Projected Dates

***

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Project Team Design

Premier Research will draw from our collection of qualified individuals to
provide BDSI with a team that has the skills, knowledge, and relevant experience
to successfully manage your clinical trial. We are organized into several
separate operational units; skill centers that perform the majority of the
day-to-day client services: Clinical Trial Management, Medical Management, Data
Operations, Biostatistics, Medical Writing, Regulatory Affairs, Quality
Assurance and Information Technology Client Services (our Interactive Voice
Response systems). Each skill center provides the resources for the services
required in drug development for their respective areas.

Project teams are the primary functional unit at Premier Research. A Project
Manager, Clinical Manager, and Biometrics Project Manager generally comprise the
leadership of the project team. With scientific guidance provided by our
therapeutic experts in Medical Affairs and senior level management and oversight
provided on every project, we offer a strong focus on your needs – leading to a
project team that is proactive, highly skilled and responsive.

The Project Manager is ultimately responsible for overall strategy, planning and
execution of the project, from start to finish. Experienced in the indication
and/or therapeutic area required, these team members provide the necessary
scientific and operational oversight to ensure that our programs and projects
stay on the critical path and that our clients receive timely and high quality
deliverables.

Another element that contributes to the success of the project team is the
Biometrics Project Manager (BPM). Because study start up is a very busy time
with the initiation of activities in all disciplines, the benefits of a BPM
joining the team maximize the attention to all details at the launch of a trial.
The management responsibility of the study is then shared between the project
manager and the BPM. The Project Manager focuses on clinical, medical, safety,
and regulatory activities while the BPM focuses on the IVRS, data management,
biostatistics, and medical writing activities. This allows the Project Manager
to spend more time on external critical relationships and increase the time
dedicated to the sites and the site staff allowing our team to build long term
networks. The Project Manager remains responsible for the clinical study from
beginning to end but has the added resource of a BPM to assist in the management
of the back end services.

Premier Research’s Parallel Processing Approach, combined with our focused
management strategy, ensures our clients the most efficient and cost-effective
clinical trial. In addition, one key team member is assigned from each skill
center and is responsible for the major set of tasks and deliverables provided
by his or her skill center. Each project team is completed by a number of
contributors; individuals with backgrounds and expertise from their skill
centers that are needed to satisfactorily execute the requirements of a given
project.

The project team will exist for the duration of the project. However, the amount
and continuity of time spent on the project will vary depending on the role of
the individual assigned to the project. The project team will receive support
from the heads and line managers within the skill centers, along with senior
management when needed.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Premier Research believes that this team structure:

 

•  

Ensures the efficient use of each team member’s knowledge and experience,

 

•  

Ensures the focused management of each individual study,

 

•  

And provides overall guidance for all projects and programs, ensuring
comprehensive project operations, team integration and seamless execution of the
program.

We have provided an organizational chart displaying the structure of this team,
and we have also included biographical sketches of our team leaders to
demonstrate why BDSI can be assured that it will be working with a skilled and
knowledgeable team.

BDSI/Premier Research Project Team Organizational Chart

LOGO [g77692ex10_1pg10.jpg]

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Project Team Leadership

Michael Kuss, BS

Vice President, Clinical Research Center Administration

Mr. Michael Kuss has worked for Premier Research Group since 2001. He currently
is the Vice President of the Clinical Research Centers. He previously served as
the Vice President of Medical Affairs in Analgesia and as the Executive
Director, Clinical Trials Management for three years and worked as a Senior
Director, Analgesia and Rheumatology, (SCIREX Corporation). From 1986 to 2001 he
worked for Pharmacia (formerly G.D. Searle) in various positions with the last
being Director of Research and Development. Prior to G.D. Searle, Mr. Kuss
worked as a Clinical Research Associate, (Abbott Laboratories), and as an
Infectious Diseases Research Technologist, (Good Samaritan Hospital and Wright
State University SOM).

While at Premier Research Group, Mr. Kuss has worked primarily on projects in
the Analgesia and Rheumatology area. He is responsible for working with clients
to help develop clinical development plans, write protocols, manage Premier
study teams to conduct clinical trials and participate in the preparation of
clinical study reports. At Pharmacia, Mr. Kuss was responsible for clinical
development of several COX-2 inhibitors (celecoxib, valdecoxib and parecoxib)
and NSAIDs (oxaprozin, oxaprozin potassium and diclofenac/misoprostol) as part
of the Arthritis and Inflammation team. He also played an integral part in the
development of lomefloxacin, a quinolone anti-infective. He is an author on many
publications and posters in the areas of analgesia, rheumatology and infectious
diseases.

Mr. Kuss graduated from Wright State University in Dayton, Ohio with a BS in
Medical Technology. He received a certification in Medical Technology from the
American Society of Clinical Pathology.

Mr. Kuss is a member of the American Pain Society and Drug Information
Association. He is a frequent presenter at annual meetings of the American Pain
Society and American College of Rheumatology annual meetings. He has presented
at the DIA annual meeting and at several DIA sponsored symposia.

Clinical Executive Leadership

Stephen Daniels, DO

Executive Medical Director, Clinical Research Center Administration

Dr. Stephen Daniels is the Executive Director of the Research Centers, a
position he has held for over five years. Dr. Daniels has served as principal
investigator on numerous acute pain trials, including many in dental,
bunionectomy, knee arthroscopy and dysmenorrhea which involved oral, parenteral,
and intranasal analgesics.

Prior to joining Premier Research, Dr. Daniels spent two years as the Medical
Director at Research for Health in Houston, TX and prior to that was Medical
Director as RLC Healthcare. Dr. Daniels is a graduate of Texas Wesleyan College
and Texas College of Osteopathic Medicine where he received his D.O.

Over the past 5 years Dr. Daniels has authored or co-authored 12 publications in
peer-reviewed medical journals and provided medical oversight on all acute pain
analgesic trials conducted within the Clinical Research Centers.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Craig Dale, BBA

Executive Director, Clinical Trial Management

Mr. Dale has worked for Premier Research Group since 1998. He currently works as
Executive Director, Clinical Trial Management. Previous to that, he worked as a
Senior Director, Clinical Trials Management (2005 - 2007), as a Project
Director, General Medicine, (2001 - 2005) and as Senior Project Manager, General
Medicine, (1998-2001). He will be available to consult with the project team
during these studies and will act as a liaison with BDSI as needed. Mr. Dale’s
supervision is part of Premier Research’s commitment to quality assurance and is
offered at no charge to BDSI.

From 1990 to 1998, Mr. Dale worked for Pharmaceutical Product Development (PPD)
in various positions with the last being Senior Project Manager. While at
Premier Research Group, Mr. Dale has worked primarily on projects in the General
Medicine and Analgesia therapeutic areas including cardiovascular,
gastroenterology and pain management. He is responsible for working with clients
to help develop clinical development plans, provide therapeutic expertise to
internal and external clients, manage Premier study teams to conduct clinical
trials and participate in the preparation of clinical study reports.

Mr. Dale graduated from the University of Mississippi in Oxford, MS with a BBA
in Marketing. He is a member of the American Pain Society and Drug Information
Association.

Project Manager

Daniel Solorio, BS

Senior Project Manager, Clinical Research Centers

Mr. Solorio is responsible for overseeing the clinical operations of one or more
multi-disciplinary project teams conducted in the clinical research centers. In
this role, Mr. Solorio ensures that the project team has a common understanding
of project objectives, specifications, deliverables, timelines and tasks.

Mr. Solorio began his career in 1996, and has been with Premier Research since
2000 focusing his experience in clinical site operations. Prior to becoming a
Project Manager, Mr. Solorio worked two years as a Site Manager, one year as a
Clinical Research Coordinator, and one year as a Supervisor for Clinical
Research Coordinators at the Clinical Research Center in Salt Lake City, UT.

Mr. Solorio received his B.A. in Communications from the University of Utah.

Biometrics Project Management

Lisa Vickers, BA

Biometrics Project Manager

As a Biometrics Project Manager (BPM), Ms. Vickers is responsible for the
overall project management of the data management, statistics and medical
writing services. Ms. Vickers has worked on numerous Phase I to Phase IV
projects in oncology, CNS, cardiovascular, endocrinology, urology, women’s
health, immunology, dermatology, and respiratory.

Lisa Vickers has been in the Manager, Biometrics position with Premier Research
Group since January 2006. Ms. Vickers was employed with PharmData Inc. as a
Biometrics Project Manager from November 2003. Prior to that Ms. Vickers worked
as both a Medical Writer and Project Assistant at PharmData and held positions
of increasing responsibility at WorldCom.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Ms. Vickers obtained a Bachelor’s degree in Psychology and a Bachelor’s degree
in Marketing from Miami University in Oxford, OH. Ms. Vickers is a member of DIA
and was a member of the American Medical Writers Association for 3 years,
serving as Membership chair from 2002-2003.

An experienced BPM will be assigned to BDSI’s program upon finalization of the
protocol.

Biostatistics

James Johnson, PhD

Executive Director, Global Biostatistics

Dr. James Johnson is the Executive Director, Global Biostatistics with overall
responsibility for strategic and tactical management for biostatistics,
pharmacokinetics and biostatistical programming functions for the Premier
Research. He is responsible for implementing best biostatistical and statistical
programming practices, standard operating procedures, and a systems approach
integrated clinical/statistical critical thinking toward drug development and
clinical trial design and analysis.

Dr. Johnson has twenty-five years technical experience and leadership in
Biostatistics, Clinical Trials Design and Analysis, Project Management, and
International Regulatory Agency interaction. In addition Dr. Johnson provides
biostatistical consulting services in the areas of cardiology, oncology,
dermatology, and infectious diseases. Dr. Johnson serves on data monitoring
committees and is a sub-principal investigator for a long term cardiac imaging
study. Dr. Johnson has also been the lead biostatistician on five New Drug
Applications, supported six additional ANDAs, and participated in many different
international regulatory interactions (FDA, MHRA, EMEA, Health Canada, and
Australian TGA) in his career.

Dr. Johnson holds a PhD degree from North Carolina State University, along with
a Master’s degree from the College of William and Mary. He is an author of over
30 publications, abstracts, and professional meeting presentations.

An experienced Biostatistician will be assigned to BDSI’s program upon
finalization of the protocol and award of the program and will work under the
direct supervision of Dr. Johnson to support this project.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Project Implementation Plan

Project Plan Development

Premier Research believes that establishing a clear and agreed upon project plan
between BDSI and Premier Research prior to study start up activity is critical
to the success of any collaboration. Working in concert, the leadership team for
each study develops a study-specific project plan detailing project specific
information and procedures to be used to carry out the activities of the
clinical team. The plan will include a description of the project team and any
metrics used to assess performance.

In addition, the project plan will determine appropriate communication channels,
identify expectations, processes and responsibilities, and define study
timelines, interim turnaround times, and critical path milestones for both
Premier Research and BDSI.

Parallel Processing Approach™

Premier Research has developed a simple but highly effective strategy, the
Parallel Processing Approach™ (PPA), to ensure quality, speed and
cost-effectiveness. We have tested, refined, and perfected this approach over a
twelve year period on over 400 projects. Using the Parallel Processing Approach,
each biometrics discipline initiates and processes its part of the project as
quickly as possible. As soon as the study protocol and CRF are finalized, the
data management group begins the database design, the statistical group begins
the statistical analysis plan (SAP) and identification of feasibility checks and
the medical writing group begins the shell report. As data arrives, it is
cleaned and entered. Edit checks are run against new data and these subsets of
(blinded) data are used to test and validate the statistical analysis programs.
The writers lay out the format of the report, including all tables, figures, and
listings defined in the SAP, per FDA and ICH guidelines.

In short, all the critical processes and procedures are conducted simultaneously
so that by the time the final CRF data is entered and validated, all the SAS
programming, the study report format, and table, graph, and analysis formats
have been completed and agreed upon. Once the report is generated, an extensive
‘end-to-end’ review procedure is executed during which all data and results of
the study are quality controlled. Because extensive ‘pre-reviews’ have already
been done and incorporated for style, format and content issues, the final
review is extremely efficient and ensures a high quality product is delivered
quickly.

Start-up Activities

 

1. Team Training and Meetings

The availability of a final protocol and informed consent and assent templates
at the beginning of the study will prevent unnecessary delays in supporting the
sites with IRB submissions. Following the award of a project, the core project
team, including the support of senior clinical trial management staff and
business development, hold a ‘hand-over’ meeting that serves as the first step
in launching a clinical trial at Premier Research. Because departments within
our company work closely together, the project team is well informed and we will
be prepared to act quickly to initiate the start of this study.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Premier Research generally holds a project kick-off meeting with BDSI. SOP,
therapeutic and study specific training are tantamount to Premier Research’s
practice of quality team performance, thus, this training is combined with the
kick-off meeting and/or the Investigators’ Meeting.

Prior to conducting initiation visits, CRAs are provided with a study-specific
agenda and associated presentation to ensure consistent dissemination of study
information. CRAs will have been trained with regard to the expectations for the
following: query/issue resolution, site communication, project team
communication, and routine visit report writing.

 

2. Collection of Essential Documents and IRB Submission

At the outset, several members of the Premier Research project team will be
dedicated to the review and collection of regulatory documents from the
investigative sites. The entire process will be closely managed and incorporate
several means of communication between Premier Research and the sites to reduce
errors and expedite the receipt of accurate critical documents.

Key to the management of regulatory submission is the tracking of IRB review
meetings. This task is undertaken by the Premier Research clinical trial
management team and tracked closely throughout the course of study start-up.
Compared to local site IRB review periods that can take two to three months (if
not more at times), central IRBs that Premier Research has working experience
with have an average review period of two to four weeks. Sites that can use
Central IRBs will be key and the first to come on board with initiation and
enrollment, with the local sites showing enrollment a bit later in the course of
the study.

Upon receipt of approval from the IRB, each site will be contacted for an
initiation visit. During these visits the CRA will instruct the site personnel
in the technical aspects of the study, including conduct of the study protocol,
CRF completion, study drug and related materials, and adverse event reporting.

Enrollment Plan

Premier Research places a strong focus on ensuring the sites are aware, at the
qualification visit and re-confirmed during their initiation visit, of the
enrollment expectations and the steps that may occur if the expectations are not
met. These steps include on-site monitoring visits with Investigator attendance
required to discuss recruitment obstacles to the plan communicated at
qualification and initiation visits, along with possible site closure if
enrollment does not commence within the agreed upon timeframe communicated
during the qualification visit. While reviewing these expectations, Premier
Research also has found it beneficial that the roles of the individuals who are
responsible for subject recruitment be clearly defined, documented and confirmed
by the Principal Investigator.

Our approach is to institute frequent contact between site staff, the assigned
CRA and the Project Management team to ensure immediate identification of
problems related to recruitment that may arise that were unanticipated.
Ownership and accountability of recruitment and meeting the enrollment goals as
expected is a joint effort with the sites and Premier Research and as such,
collaboration and constant reinforcement of the goals of the study is a key to
success.

Communication

Strong communication is essential to a successful project and will be conducted
according to the Project Plan. Communications may include but are not limited to
overall study status, outstanding and critical issues, patient enrollment and
budget status.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Communications will be conducted via telephone, fax, postal and electronic mail
as needed. Teleconference calls will be held as necessary, and as indicated
below.

Primary Contacts

The Project Manager facilitates communication between BDSI and Premier Research;
however, the Clinical Manager, as well as all team members, is available to
communicate with the BDSI team as needed.

Sponsor Teleconferences

Teleconferences are held between the Premier Research team and BDSI as noted in
the table below. The day and time of these calls will be mutually decided upon
by the Project Manager and BDSI. Participants are noted in the table below;
however, the Executive Director, or any other Premier Research team member would
attend on an ‘as needed’ basis. Agendas are provided the day before the
regularly scheduled call and minutes will be taken and provided to BDSI. BDSI is
asked to review the minutes and approve for finalization.

The following table is a general outline of our planned communication with BDSI
as well as planned internal meetings with Premier Research staff members.

 

Meeting

  

Frequency

  

Premier Research Attendees

Project Kick-off Meeting    One time    All key team management Training Meeting
– often held in conjunction with the Kick-off    One meeting    See above
Teleconferences with BDSI    Weekly    Project Manager, Clinical Manager,
Biometrics Project Manager, additional team members as needed Teleconferences
with Vendors    As needed    Project Manager, additional team members as needed
Internal Project Management Teleconferences    Weekly    Project Manager,
Clinical Manager, Biometrics Project Manager, Key team members as needed
Internal Teleconferences with CRAs    Weekly    Project Manager (as needed),
Clinical Manager, CRAs

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Price Summary

The following table presents a summarized cost estimate. Please see the Detailed
Cost Estimate for a more detailed breakdown of costs. Please note that these
costs are estimates only. The budget will be finalized upon award of the project
and provision of final project scope. Should the scope or size of the project
increase or decrease, the estimates will be revised accordingly in writing and
agreed upon by both parties.

If protocol design modifications change the scope of work to be provided, or if
additional services are requested beyond the scope of this proposal, Premier
Research and BDSI will discuss and negotiate any appropriate revisions to the
costs involved.

This budget estimate is valid for 90 days following the date of this proposal.

 

BioDelivery Sciences International, Inc.

Protocol: BUP-201

   Estimated
Costs

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

***

     ***

Project Grand Total

   $ 1,199,271

NOTE: ***

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Detailed Cost Estimate

Please note that these costs are estimates only. The budget will be finalized
upon award of the project and provision of final project scope. Should the scope
or size of the project increase or decrease, the estimates will be revised
accordingly in writing and agreed upon by both parties.

If protocol design modifications change the scope of work to be provided, or if
additional services are requested beyond the scope of this proposal, Premier
Research and BDSI will discuss and negotiate any appropriate revisions to the
costs involved.

This budget estimate is valid for 90 days following the date of this proposal.

 

BioDelivery Sciences International, Inc.

Protocol: BUP-201

   Estimated
Costs

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

BioDelivery Sciences International, Inc.

Protocol: BUP-201

   Estimated
Costs

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

BioDelivery Sciences International, Inc.

Protocol: BUP-201

   Estimated
Costs

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

***

   ***

Project Grand Total

   $1,199,271

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Notes on Pass-through Estimates

Pass-through costs are estimated to provide a “total budget scenario” for your
review. These costs are estimated given currently available information and
historical averages. Every effort will be used to minimize these costs and the
final pass-through budget will be worked out with BDSI in advance of study
start.

***

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Clinical Research Center Investigator Grant Summary

PREMIER RESEARCH - INVESTIGATOR GRANT BUDGET

BioDelivery Sciences International, Inc.

***

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Service Descriptions

The following are general descriptions of the services that Premier Research is
offering to provide during the

course of this study. These descriptions are designed to be a summary of the
concepts found in the Premier

Research Standard Operating Procedures (SOPs) but are not an exact replica of
these procedures. Unless

noted otherwise in this proposal, Premier Research’s budget estimate is based
upon the use of Premier

Research SOPs.*

 

  1.1. Protocol Development and Review

 

  1.1.1. BDSI will be responsible for delivery of a final protocol to Premier
Research.

 

  1.2. eCRF Preparation

 

  1.2.1. eCRF Development

 

  1.2.1.1. BDSI will be responsible for development of the eCRF for this study.

 

  1.3. Subject Assessment Booklet Development and Review

 

  1.3.1. Subject Assessment Booklet Development

 

  1.3.1.1. Premier Research will not develop traditional patient diaries, but
will develop an in-house assessment booklet to capture all of the patient pain
assessment data. Premier Research will provide BDSI with a draft of the in-house
subject assessment booklet for approval for the study.

 

  1.3.1.2. Premier Research will prepare the subject assessment booklet in
English.

 

  1.3.1.3. BDSI will be provided with a copy of the final approved subject
assessment booklet.

 

  1.3.2. Subject Assessment Booklet Distribution

 

  1.3.2.1. Premier Research will determine site form needs and distribute
diaries accordingly over the course of the study.

 

  1.3.2.2. Premier Research shall arrange for storage of diaries at an
appropriate location.

 

  1.4. Study Materials Development

 

  1.4.1. Model Informed Consent Form (ICF) Development

 

  1.4.1.1. Premier Research will review the protocol, Investigators’ Brochures,
etc. and discuss all study parameters with BDSI to fully understand the
associated subject benefits and risks.

 

  1.4.1.2. Premier Research will follow BDSI’s sample ICF, if provided.

 

* Premier Research will carry out these services pursuant to the protocol;
local, state, and federal regulations; and ICH/GCP guidelines. All study
activities will be performed according to Premier Research SOPs, unless
otherwise noted. Premier Research will make available, upon request, its SOPs
for BDSI review. It is Premier Research policy that copies of SOPs cannot be
provided; however, BDSI may review the SOPs at any Premier Research office. If
BDSI requests activities to be performed according to its SOPs, budget
modifications may be necessary.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  1.4.1.3. Premier Research will review the list of FDA-required ICF elements to
ensure compliance. Premier Research will also review state ICF requirements to
ensure compliance (e.g., State of California, Bill of Rights).

 

  1.4.1.4. Premier Research will prepare a draft Model ICF to be circulated to
the Premier Research Project Teams for internal review and comment.

 

  1.4.1.5. Premier Research can arrange for certified translation of the Model
ICF, if necessary.

 

  1.4.1.6. Premier Research will incorporate Project Team comments, as
appropriate, and provide the draft Model ICF (up to two drafts) for BDSI review.
Any comments from BDSI will be consolidated before being returned to Premier
Research.

 

  1.4.1.7. Premier Research will incorporate BDSI’s consolidated comments and
produce a final Model ICF for BDSI’s approval.

 

  1.4.1.8. Premier Research will make the approved Model ICF available to all
investigative sites as a template to be used to generate their site-specific
ICF. Premier Research will review the site-specific ICF for each investigative
site to ensure that it remains in compliance with FDA, state, and BDSI required
ICF elements.

 

  1.4.1.9. Premier Research can arrange for certified translation of the
site-specific ICFs, if necessary.

 

  1.4.2. Source Document Development

 

  1.4.2.1. Premier Research will develop a standard source document. This
document will help to assure all required data points are appropriately captured
per the protocol and it will help expedite the CRF review process during
monitoring visits.

 

  1.4.3. Clinical Plan Development

 

  1.4.3.1. The Premier Research Project Manager, in conjunction with the Premier
Research Project Director, will develop a Clinical Plan. This document details
project specific information and the procedures to be used to carry out the
activities and services provided by the clinical department.

 

  1.4.4. Regulatory Binder Setup

 

  1.4.4.1. Premier Research will set up for each Investigator a binder that will
contain all relevant study documents.

 

  1.4.4.2. This binder should contain, but not be limited to, the following:

 

  1.4.4.2.1. Monitoring Sign-In Log,

 

  1.4.4.2.2. Randomization List/Emergency Envelopes (where applicable),

 

  1.4.4.2.3. Receipt/Retrieval documentation for drug/other study supplies,
including eCRFs/diaries,

 

  1.4.4.2.4. Drug Accountability Forms (where applicable),

 

  1.4.4.2.5. Laboratory Certification and normal ranges (where applicable),

 

  1.4.4.2.6. Enrollment/Exclusion Log,

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  1.4.4.2.7. Sample of Model ICF and site-specific ICF,

 

  1.4.4.2.8. Study Center Sample Signature Form,

 

  1.4.4.2.9. CVs for Investigator, Sub-Investigator, and other key personnel,

 

  1.4.4.2.10. Signed, original Protocol and all amendments,

 

  1.4.4.2.11. IRB/Ethics Committee approval(s),

 

  1.4.4.2.12. Essential documents (e.g., FDA-1572, submissions),

 

  1.4.4.2.13. Letter of indemnity (where applicable),

 

  1.4.4.2.14. National guidelines and legal information on clinical trials
(where applicable),

 

  1.4.4.2.15. Investigators’ Brochure,

 

  1.4.4.2.16. Signed Confidentiality Agreement,

 

  1.4.4.2.17. Correspondence regarding the study, including written telephone
contact forms,

 

  1.4.4.2.18. Instructions for eCRF/diary completion,

 

  1.4.4.2.19. Procedures for AE/SAE reporting and completed SAE report forms,

 

  1.4.4.2.20. Handling of clinical laboratory samples,

 

  1.4.4.2.21. The name of the appropriate Premier Research contact for specific
issues (e.g., SAE reporting), and

 

  1.4.4.2.22. Instructions for ordering study supplies.

 

  1.4.4.3. Premier Research will distribute the final Regulatory Binder to the
Investigators.

 

  1.4.4.4. Financial agreements, payment schedules, and correspondence regarding
investigator payment will be maintained in a file separate from the Regulatory
Binder.

 

  1.4.5. Study File Setup

 

  1.4.5.1. Premier Research will set up and keep study documents in the Study
File.

 

  1.4.5.2. This file shall contain, but not be limited to, the following
documentation:

 

  1.4.5.2.1. All study-related correspondence,

 

  1.4.5.2.2. Serious Adverse Event reports,

 

  1.4.5.2.3. Receipt/Retrieval forms for drug and other study supplies,

 

  1.4.5.2.4. Meeting information,

 

  1.4.5.2.5. Client-approved study protocol and amendments,

 

  1.4.5.2.6. Sample eCRF and supplemental data forms will be provided in the
investigator binder and will be used only as emergency back up if for any reason
the system may become non-operational,

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  1.4.5.2.7. Sample subject instructions, Model ICF, and advertising,

 

  1.4.5.2.8. Investigators’ Brochure or Package Insert,

 

  1.4.5.2.9. Data Operations Guidelines,

 

  1.4.5.2.10. IRB/Ethics Committee approval(s),

 

  1.4.5.2.11. Regulatory approval(s), and

 

  1.4.5.2.12. Reports (interim/final).

 

  1.4.6. Translations

 

  1.4.6.1. Premier Research will not be responsible for any document
translations.

 

  1.4.7. Statistical Analysis Plan (SAP) and TLG Shell Review

 

  1.4.7.1. The Project Manager will review the SAP prior to finalization.

 

  1.5. Investigator Identification and Recruitment

 

  1.5.1. Premier Research will utilize the Clinical Research Centers for this
trial.

 

  1.5.2. Premier Research will review FDA’s Disqualified Investigators list, and
FDA’s Monitoring Inspection Log to ensure that potential Investigators are
qualified to conduct the study.

 

  1.5.3. Premier Research will send to each Investigator (if appropriate) a
Confidentiality Agreement, protocol/protocol synopsis, and Investigators’
Brochure.

 

  1.5.4. Premier Research will discuss briefly with each Investigator:

 

  1.5.4.1. Overview of BDSI,

 

  1.5.4.2. Study compound,

 

  1.5.4.3. Therapeutic area being studied,

 

  1.5.4.4. Study procedures/assessments,

 

  1.5.4.5. Number and availability of subjects to be recruited,

 

  1.5.4.6. Study duration, complexity, and the investigators’ clinical workload,

 

  1.5.4.7. Subject inclusion/exclusion requirements, and

 

  1.5.4.8. Study budget (i.e., investigator payments), if appropriate.

 

  1.6. Prestudy Site Reviews

 

  1.6.1. Premier Research will perform prestudy site reviews to:

 

  1.6.1.1. Discuss the study and impart obligations and responsibilities,

 

  1.6.1.2. Determine whether suitable subject population exists,

 

  1.6.1.3. Obtain pre-study documentation and essential documents when
available, and

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  1.6.1.4. Assess ability to begin the study in a timely fashion.

 

  1.6.2. Premier Research will not discuss BDSI’s company or drug name without
confirming that the Investigator has signed a Confidentiality Agreement.

 

  1.6.3. Premier Research will follow up the prestudy review with the following
tasks:

 

  1.6.3.1. Provide a summary of discussions, action items, requests for any
outstanding documentation, etc. for suitable Investigators and

 

  1.6.3.2. Retrieve all confidential information from Investigators designated
not suitable.

 

  1.7. Collection of Essential Documents

 

  1.7.1. Premier Research will be responsible for collecting essential documents
from investigators selected for participation in this clinical trial, including
the following:

 

  1.7.1.1. A signed FDA Form 1572,

 

  1.7.1.2. A signed protocol signature page, if used,

 

  1.7.1.3. A current, signed CV for Principal Investigator and
Sub-Investigators,

 

  1.7.1.4. An IRB Approval,

 

  1.7.1.5. An IRB-approved Informed Consent Form,

 

  1.7.1.6. The financial disclosure documents,

 

  1.7.1.7. A list of IRB members/Department of Health and Human Services
Assurance Number,

 

  1.7.1.8. Laboratory certifications, and

 

  1.7.1.9. The normal ranges of laboratory tests or reference ranges for
laboratory analyses.

 

  1.7.2. Premier Research will provide BDSI with all original essential
documents after reviewing all essential documents for accuracy and completeness.

 

  1.7.3. BDSI will be responsible for filing these documents for the IND.

 

  1.8. Investigator Grant and Contract Negotiation

 

  1.8.1. Premier Research will set up a payment program based on the procedures
outlined in the final protocol. Payments will be made on a prorated basis of
work performed as set out in the final contract.

 

  1.8.2. The grant amounts will cover all protocol procedures, institutional
overheads, study coordinator fees, subject stipends, and advertising costs.
Premier Research will execute final contracts with each investigator and will
process investigator payments based on the payment plan outlined in the
negotiated clinical study agreements.

 

  1.9. Investigators’ Meeting

 

  1.9.1. Due to the minimal number of investigational sites and their recurring
experience with this type of study, Premier Research has assumed that an
Investigators’ Meeting is unnecessary.

 

  1.10. Training

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  1.10.1. Project Specific Training

 

  1.10.1.1. Premier Research will ensure that all appropriate project staff are
adequately trained in all the clinical and administrative aspects of the study
including the following:

 

  1.10.1.1.1. Study protocol,

 

  1.10.1.1.2. Study plans and targets,

 

  1.10.1.1.3. Instructions to investigators,

 

  1.10.1.1.4. Study documents, and

 

  1.10.1.1.5. Clinical and administrative procedures, including consent waiver
regulations.

 

  1.11. Vendor Selection and Consulting

 

  1.11.1. Institutional Review Board (IRB) Selection and Setup

 

  1.11.1.1. Premier Research will be available to assist the sites in obtaining
the required IRB approvals.

 

  1.11.1.2. Premier Research will make the protocol, CRF, Diary, Investigators’
Brochure, and Model ICF available to the central IRB for review and comment, if
necessary or requested by BDSI.

 

  1.11.1.3. Premier Research will provide a copy of protocol amendments to
investigators after the amendments are finalized with BDSI and appropriate
regulatory agency approval.

 

  1.11.2. Vendor Selection and Setup

 

  1.11.3. BDSI will identify the necessary vendors and set up vendors for study
participation.

 

2. Project Management

 

  2.1. Client Interaction

 

  2.1.1. Premier Research will communicate with BDSI management on a regular
basis concerning the study and its progress.

 

  2.1.2. Client Teleconferences

 

  2.1.2.1. Premier Research assumes teleconferences between key project members
and BDSI at the frequency indicated in the “Project Outline.”

 

  2.1.3. Ad Hoc Client Communications

 

  2.1.3.1. Premier Research anticipates that members of the project team will
communicate informally with BDSI on a regular basis.

 

  2.2. Project Team Management

 

  2.2.1. Internal Project Team Meetings

 

  2.2.1.1. Appropriate members of the Premier Research project team will attend
regular internal meetings as necessary.

 

  2.2.1.2. Premier Research will record major team meeting minutes for
distribution.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  2.2.2. Internal Team Support

 

  2.2.2.1. The Premier Research team leader will perform the following general
management functions for this study:

 

  2.2.2.1.1. Coordinate and manage the project team, including ad hoc training,
resource management, mentoring, and support deemed necessary for the smooth
execution of this project;

 

  2.2.2.1.2. Manage project costs, schedules, and quality to ensure that study
goals and objectives are achieved;

 

  2.2.2.1.3. Manage sub-contractors (i.e., external data sources, drug
packaging/distribution, etc.) to ensure smooth interaction with other aspects of
the study;

 

  2.2.2.1.4. Ensure invoices sent to BDSI are appropriate for work performed;
and

 

  2.2.2.1.5. Ensure that work carried out is in accordance with Premier Research
SOPs; ICH/GCP guidelines; and local, state, and federal regulations.

 

  2.3. Project Tracking

 

  2.3.1. Project Tracking and Status Reports

 

  2.3.1.1. This proposal is based on the tracking and compilation of the
following information: site information (contact information for the Principal
Investigator and Study Coordinator); patient enrollment, visit, and disposition
information (on a weekly basis); and grant payment information. Premier Research
can track additional information to meet BDSI-specific study requirements;
however, significant additions may incur additional labor costs.

 

  2.3.1.2. Premier Research will provide a progress report on a monthly basis.
The report will show the number of subjects enrolled in the study and the stage
of each subject in the trial, copies of correspondence generated in the previous
month, copies of trip reports completed in the previous month, etc. The format
for this report will be discussed with and approved in advance by BDSI. Premier
Research can provide more frequent progress reports to meet BDSI-specific study
requirements; however, significant additions may incur additional labor costs.

 

3. Clinical Monitoring and Site Management

 

  3.1. Initiation Visits

 

  3.1.1. Premier Research will provide investigators with an Investigators’ File
prior to site initiation to ensure proper investigator file maintenance.

 

  3.1.2. Premier Research will maintain copies of all essential documents,
unless specified otherwise by BDSI. Premier Research will maintain original
correspondence and provide BDSI with copies at the end of the study, unless
specified otherwise by BDSI.

 

  3.1.3. Premier Research will perform initiation visits at each site according
to Premier Research SOPs. During these visits, Premier Research will instruct
the Investigator and the study coordinator in the technical aspects of the
study, including but not limited to:

 

  3.1.3.1. Conduct of the study protocol,

 

  3.1.3.2. Training on the eCRF data collection system,

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  3.1.3.3. Specimen handling for laboratory evaluation and pharmacokinetic
evaluation (if applicable),

 

  3.1.3.4. Inventory of the study drug and all related materials, and

 

  3.1.3.5. Adverse Event/Serious Adverse Event reporting.

 

  3.1.4. For each site visited, Premier Research will complete an initiation
visit report according to Premier Research SOPs and make it available to BDSI
within 15 business days of the visit.

 

  3.2. Investigator Site Grant Administration

 

  3.2.1. Premier Research will administer all Investigator payments and account
for them according to Generally Accepted Accounting Principles (GAAP).

 

  3.2.2. BDSI is expected to provide Premier Research with adequate funds to
administer the Investigator payments.

 

  3.3. Study File Maintenance

 

  3.3.1. Premier Research will ensure all files in the Study Files are kept
current, including updated essential documents and copies of all correspondence.

 

  3.3.2. Premier Research will also maintain, in the Study File, financial
agreements, payment schedules, and correspondence regarding investigator
payments.

 

  3.3.3. Protocol amendments may be required during the course of this trial.
Premier Research will maintain copies of all protocol amendments in the Study
File. In addition, copies of amendments will be provided to each site for IRB
submission and inclusion in the Investigator File. Premier Research standard
labor estimate includes the administrative activities for up to two protocol
amendments.

 

  3.4. Routine Monitoring Visits

 

  3.4.1. Premier Research shall conduct routine monitoring visits at each site
at a frequency specified in the “Project Outline.” Trained Clinical Research
Associates (CRAs) will perform all monitoring.

 

  3.4.2. BDSI personnel are welcome to accompany Premier Research staff on any
visit.

 

  3.4.3. For each visited conducted, Premier Research will complete a monitoring
visit report according to Premier Research SOPs and make it available to BDSI
according to the study-specific monitoring plan. This report will include, but
not be limited to:

 

  3.4.3.1. Subject accrual status report with the number of subjects entered,
dropped, and completed;

 

  3.4.3.2. Issues related to subject accrual;

 

  3.4.3.3. Issues related to subject safety;

 

  3.4.3.4. eCRF/diary collection;

 

  3.4.3.5. Status of regulatory documents;

 

  3.4.3.6. Status of drug accountability; and

 

  3.4.3.7. ICH/GCP guidelines.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]

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

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  3.4.4. A detailed follow-up letter will also be sent to the Investigator
outlining the pertinent points from each visit and the agreed upon actions.

 

  3.4.5. One hundred percent (100%) Source Document Verification will be
performed.

 

  3.4.6. Premier Research will consolidate and update the subject accrual status
report on a regular basis as directed by BDSI.

 

  3.4.7. Premier Research will notify BDSI whenever accrual rates fail to attain
the predicted rates.

 

  3.4.8. The CRAs (along with the Project Manager) will be responsible for:

 

  3.4.8.1. Routinely reviewing enrollment reports,

 

  3.4.8.2. Providing scheduled status updates,

 

  3.4.8.3. Writing and distributing newsletters to Investigators (if requested),

 

  3.4.8.4. Ensuring proper drug accountability,

 

  3.4.8.5. Reviewing site essential documents (collecting and transmitting to
BDSI as needed),

 

  3.4.8.6. Managing protocol amendment submissions to the IRB(s), and

 

  3.4.8.7. Reporting Serious Adverse Events.

 

  3.4.9. The CRAs will ensure the study drug is secured and accountability
records are accurate and updated.

 

  3.4.10. The CRAs will conduct a continuing review of the Investigators’ File
for regulatory adherence.

 

  3.5. Interim Site Communications

 

  3.5.1. Premier Research CRAs will maintain ongoing communication with each
site between monitoring visits to ensure close tracking of study progress.

 

  3.5.2. Substantive communications will be documented in telephone logs and
memos.

 

  3.5.3. Copies of the telephone contact reports and memos will be distributed
to specific Premier Research Team members and BDSI (as described above).

 

  3.6. SAE Administration

 

  3.6.1. Premier Research Clinical Trials Management will receive copies of
completed SAE forms from Premier Research Medical Management. Premier Research
Clinical Trials Management will assist Premier Research Medical Management in
retrieving requested follow-up information if requested and will receive
completed follow-up SAE forms from Premier Research Medical Management.

 

  3.6.2. Premier Research Clinical Trials Management will track SAE information
to ensure appropriate follow-up and distribution but is not responsible for
detailed or specialized tracking and reporting on SAE information.

 

  3.6.3. Premier Research Clinical Trials Management will receive IND Safety
Reports from BDSI and provide them to the investigational sites. Premier
Research will track IRB acknowledgement of these IND Safety Reports.

 

  3.7. Response to QA Audits

 

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4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  3.7.1. Premier Research will review each audit report and discuss findings
with the auditor.

 

  3.7.2. The CRA will work with the Clinical Manager and the site to resolve any
findings in the audit report.

 

  3.7.3. Responses will be provided to the auditor and included in the final
audit report that is submitted to BDSI.

 

  3.8. Newsletters

 

  3.8.1. Premier Research will not provide newsletters for this study.

 

  3.9. Closeout Visits

 

  3.9.1. Premier Research CRAs will conduct closeout visits to each
investigational site.

 

  3.9.2. Closeout visits will include the following tasks:

 

  3.9.2.1. Ensure that all CRF data and data queries (if applicable) has been
entered into the data collection system,

 

  3.9.2.2. Review of the Investigators’ File for completeness and regulatory
compliance,

 

  3.9.2.3. Management of final drug accountability and reconciliation,

 

  3.9.2.4. Discussion with study staff regarding continuing responsibilities,
and

 

  3.9.2.5. Arrangement for record retention.

 

  3.9.3. Premier Research shall ensure that study documents including, but not
limited to, the following are in order at the investigational site:

 

  3.9.3.1. Copies of the Signed IRB-Approved Informed Consent Forms and other
documentation,

 

  3.9.3.2. Copies of FDA Form 1572 signed during the study,

 

  3.9.3.3. Laboratory Certification and Laboratory Reference Ranges,

 

  3.9.3.4. Copies of all CRFs/diaries and correction forms,

 

  3.9.3.5. Source Documents,

 

  3.9.3.6. Regulatory Binder,

 

  3.9.3.7. Copies of all communications (e.g., with BDSI, IRB, etc.), and

 

  3.9.3.8. Financial disclosure documents.

 

  3.9.4. Premier Research shall remove all appropriate study documentation,
CRFs/diaries, drug supplies, etc. from each investigational site.

 

  3.9.5. After completing the closeout visit, Premier Research will complete a
closeout visit report according to Premier Research SOPs and make it available
to BDSI within 15 business days of the visit. Following completion of the
report, Premier Research will send a closeout letter to the Investigator
outlining the pertinent points from the visit.

 

  3.10. IRB Maintenance and Closeout

 

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4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  3.10.1. Premier Research will manage interactions with the IRB(s).

 

  3.10.2. If requested, Premier Research will provide the final protocol and any
amendments, Investigators’ Brochure, Model ICF, and any background or
educational materials required by the IRB.

 

  3.10.3. Premier Research will work closely with each site to determine local
IRB meeting schedules and requirements, if applicable.

 

  3.11. Vendor Services Maintenance and Closeout

 

  3.11.1. BDSI will manage the interactions with contracted vendors (e.g.,
central laboratories) to ensure the smooth execution of the project.

 

  3.11.2. BDSI will administer payments to vendors.

 

4. Biostatistics

 

  4.1. Biostatistics Administration

 

  4.1.1. Meetings

 

  4.1.1.1. Biostatistics personnel will participate in the internal and external
project team meetings as needed, as noted in the “Project Outline”, conducted by
the Project Manager to discuss issues and solutions surrounding the project. All
key questions and decisions will be forwarded to BDSI.

 

  4.1.2. Data Management Plan Review

 

  4.1.2.1. Premier Research biostatistics personnel will participate in the
review of the data management plan (DMP). All other services related to the DMP
can be found in the “Data Operations” section.

 

  4.2. Protocol and Case Report Form (CRF) Review

 

  4.2.1. Premier Research biostatistics personnel will participate in the review
of the final Protocol and CRFs.

 

  4.3. Randomization

 

  4.3.1. Premier Research will develop the randomization schedule based upon
information provided in the protocol and on other information provided by BDSI,
e.g., block size.

 

  4.3.2. Premier Research will provide BDSI with a “dummy” randomization
schedule, showing the layout, format, and labeling of the treatment codes.
Premier Research will implement or respond to BDSI’s comments as appropriate.
Once BDSI approves the dummy schedule, the actual schedule will be generated
using a different random sequence. This proposal assumes one draft and one final
version of the dummy schedule.

 

  4.3.3. All processes will be done so that all parties involved with the study
remain blinded (except where unblinding is necessary such as for pharmacy
personnel preparing study medication). Emergency unblinding, e.g., in case of a
serious adverse event, will be done by the Premier Research head of Medical
Safety, according to pertinent Premier Research SOPs.

 

  4.3.4. This proposal assumes that the Premier Research biostatistics
department does not need to supply treatment codes in the form of individual
study subject sealed envelopes. Rather, the Premier Research biostatistics
department will generate and confidentially deliver a separate list for each
study site, or a single list for the entire study.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  4.3.5. Premier Research will create a randomized kit-mapping schedule for the
packaging of study drug based on information provided in the protocol and from
the sponsor and drug packager.

 

  4.3.6. This proposal assumes that the kit map consists of a simple list
matching kit numbers to treatments.

 

  4.4. Statistical Analysis Plan (SAP)

 

  4.4.1. Premier Research biostatistics personnel will develop the SAP, which
will describe in detail the analysis populations, derived variables, and
statistical methodology to be used for the final analyses. The SAP will not
include detailed analysis data set specifications or SAS programming code.

 

  4.4.2. The SAP will include “shells” (“mock-ups”) for tables, listings, and
graphs. The number of shells assumed is indicated in the “Statistical
Specifications” section of the “Project Outline” above.

 

  4.4.3. The draft SAP will be provided to the appropriate BDSI personnel for
review.

 

  4.4.4. Premier Research will implement or respond to BDSI’s comments as
appropriate and then issue the final SAP. Once BDSI approves the final plan,
preparation for programming and analyses will begin.

 

  4.4.5. This proposal assumes one draft and one final version of the SAP.

 

  4.5. Interim Analysis Programming and Production

 

  4.5.1. No interim analyses will be performed during this study.

 

  4.6. Analysis Programming and Production

 

  4.6.1. Analysis Programming

 

  4.6.1.1. Premier Research biostatistics personnel will develop programs to
create analysis data sets, which will include select derived variables required
for the analyses.

 

  4.6.1.2. Premier Research biostatistics personnel will develop programs for
the tables, listings, and graphs (TLGs) specified in the SAP. The numbers of
TLGs assumed is indicated in the “Statistical Specifications” section of the
“Project Outline” above.

 

  4.6.1.3. The programs for analysis data sets and TLGs will be checked
according to Premier Research SOPs regarding quality control of statistical
outputs.

 

  4.6.2. Analysis Production

 

  4.6.2.1. When the Premier Research biostatistics department has been provided
with the locked database, written approval from BDSI to be unblinded, and the
unblinded treatment codes, preparation for production of the analyses will
begin.

 

  4.6.2.2. Premier Research biostatistics personnel will review the data for
changes in structure or values that might require changes in programming.

 

  4.6.2.3. Premier Research biostatistics personnel will execute the programs
for the analysis data sets and TLGs, review the output, and make needed
corrections and adaptations.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  4.6.2.4. The quality control steps for the programs for the analysis data sets
and TLGs will be updated according to Premier Research SOPs regarding quality
control of statistical outputs.

 

  4.6.2.5. Following these updates and reviews, the draft TLGs will be provided
to the appropriate BDSI personnel for review.

 

  4.6.2.6. Premier Research will implement or respond to BDSI’s comments as
appropriate. The reviews and quality control steps will be updated as necessary,
after which Premier Research will issue the final TLGs.

 

  4.6.2.7. This proposal assumes one draft and one final version of the TLGs. At
BDSI’s request, the draft version may be divided into a small “top-line” set and
a complete set, with the top-line set to be provided earlier than the complete
set. The timing of the delivery of the top-line set will depend on the number
and complexity of the top-line TLGs. BDSI must specify the top-line set
following finalization of the SAP, prior to database lock.

 

  4.6.2.8. This proposal assumes that at most one hardcopy of each version
(draft or final) of the TLGs will be provided to BDSI. If additional hardcopies
are requested, additional labor, production, and shipping expenses, if any, will
be invoiced as a pass-through expense. The additional hardcopies may arrive
after the initial copy.

 

  4.7. Statistical Writing

 

  4.7.1. Integrated Clinical/Statistical Report (ICSR)

 

  4.7.1.1. Premier Research biostatistics personnel will advise the Medical
Writer regarding the statistical methods and results, including modifications or
additions to the analyses (if any) not specified in the SAP.

 

  4.7.1.2. Premier Research biostatistics personnel will review the ICSR paying
particular attention to the descriptions of statistical methods and the
interpretations of statistical results.

 

  4.8. Submission of Programs to BDSI

 

  4.8.1. Premier Research does not typically provide its analysis data set and
TLG programs to its clients. To date, Premier Research has not encountered any
instances where a client has needed the programs to successfully complete a
project. If the FDA or another regulatory agency requests the programs, Premier
Research will send the programs and appropriate documentation directly to the
regulatory agency in a timely fashion.

 

  4.9. Archiving

 

  4.9.1. Once BDSI signs the final report, Premier Research will archive all
documentation, electronic files, and programs. Premier Research will provide to
BDSI copies of all requested documentation other than the programs used to
generate analysis datasets, tables, listings, and figures.

 

5. Quality Assurance

 

  5.1. The Premier Research Quality Assurance department will provide assurance
to BDSI and Premier Research management that the study is being carried out in
accordance with the protocol, and Premier Research SOPs, local, state, and
federal guidelines and regulations.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

  5.2. Premier Research will audit the investigational sites (as indicated in
“Project Outline”) to ensure documentation is complete and in compliance with
Premier Research SOPs, and is in conformity with the Study File.

 

  5.3. Premier Research will review the study protocol (amendments, if
applicable), the CRF, and applicable Premier Research SOPs.

 

  5.4. Premier Research will check the Study File and Investigators’ Files for
completeness and adherence to the relevant Premier Research SOPs, local, state,
and federal guidelines and regulations.

 

  5.5. Premier Research will confirm subject identification and IRB/Ethics
Committee-approved informed consent documents. SAE reports (initial and final)
will be checked for all subjects against the source data.

 

  5.6. Auditors will conduct investigator site audits, independent or in
conjunction with, BDSI’s QA/Regulatory Affairs Department.

 

  5.7. At the end of each audit, a report will be written within 20 working days
of the audit and circulated to the Premier Research Project Manager.

 

  5.8. A meeting will be set up with the relevant Premier Research staff to
discuss findings and agree on responsibilities and time frames for completing
necessary actions.

 

  5.9. Resolution of deficiencies will be documented on the final audit report.

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

 

Payment Schedule

This proposal is incorporated into the Master Clinical Services Agreement
between Premier Research International LLC and BioDelivery Sciences
International as Exhibit 2.

***

Invoices Address:

David Blum, MD

Vice President, Clinical Research and Medical Affairs

BioDelivery Sciences International

801 Corporate Center Drive, Suite 210

Raleigh, NC 27607

 

Remittance Addresses:

      via Regular Mail:    via Overnight Mail:    via Wire: Premier Research
International LLC    Image Remit    Bank: Commerce Bank P.O. Box 95000-2310   
205 North Center Drive    Location: Philadelphia , PA Philadelphia, PA
19195-2310    North Brunswick, NJ 08902    Acct Name: Premier Research
International LLC    ATTN: P.O. Box 95000-2310    Acct #: 367139110       ABA
Routing #: 031201360       BIC / Swift code: CBNAUS33

ACCEPTED AND AGREED:

 

Premier Research International LLC     BioDelivery Sciences International BY:  

/s/ Dave Murcar

    BY:  

/s/ Mark Sirgo

  Dave Murcar         Director, Contract Development     TITLE:   President and
CEO DATE:  

3/12/09

    DATE:  

3/13/09

 

Confidential

4395 BioDelivery Sciences International Proposal v3

Protocol: BUP-201

   LOGO [g77692ex10_1premierresearch.jpg]