Exhibit 6.9
CONTRACT
This Agreement effective October 24,1996 ("Effective Date") sets forth the
terms under which Innapharma, Inc., 00 Xxxxxxxxxxxx Xxxx, Xxxxx Xxxxxx Xxxxx, XX
00000 (hereinafter referred to as "Innapharma,") will conduct a single center
clinical study on behalf of NexMed, Inc., 0000 Xxxxxxxx Xxxxx, Xxxxxxxx, XX
00000 (hereinafter referred to as "NexMed").
1. Innapharma will be responsible, in consultation with NexMed, for the
conduct of the NexMed VIRATROL-TM- Study entitled: "Development and
validation of safety and efficacy for a medical device in the treatment
of Herpes in a Chinese population of men or women suffering from lip
sores", as set forth in Scope of Work (Exhibit "A").
2. The Contract stipulates that Innapharma personnel will make one site
selection visit to each Ministry of Health (MOH) approved study site.
It is agreed that NexMed personnel may accompany Innapharma personnel on
such site visit. NexMed shall provide Innapharma with reasonable notice
of its intention to attend a site visit or to visit sites separately.
3. Innapharma shall promptly notify NexMed of any MOH or other inspection of
which it becomes aware, and NexMed shall have the right to be present at
any such inspection.
4. All clinical study data generated by clinical investigators or Innapharma
in connection with the study shall be the property of NexMed and is
subject to audit by NexMed, during regular business hours, at NexMed's
discretion and upon reasonable notice to Innapharma.
5. Innapharma will keep strictly confidential all information transmitted to
it by NexMed for use with the study and will require all clinical
investigators to do the same. This obligation of confidentiality shall
remain in effect for five (5) years after delivery of the data transfer
to NexMed (see Exhibit "A"). All such information will be returned
promptly to NexMed upon the completion of the project, upon termination
of this Agreement or at any time at the request of NexMed.
Notwithstanding the foregoing, Innapharma may keep in its possession a
reasonable but limited number of such documents as may be required for
regulatory, legal, insurance or record keeping purposes or which contain
information deemed by Innapharma to be privileged and/or proprietary to
Innapharma.
Information belonging to Innapharma which it designates in writing to be
confidential shall be protected from disclosure by NexMed with at least
the degree of care as used by NexMed in dealing with NexMed confidential
information.
Any and all discoveries and/or inventions by Innapharma (whether or
not patentable) relating to VIRATROL-TM- Study during or within six (6)
months after delivery of the final data transfer shall be the sole and
exclusive property of NexMed. Innapharma shall promptly notify NexMed of
any such event and assist
NexMed in the protection of NexMed's proprietary rights to such
discoveries and/or inventions. Notwithstanding the foregoing,
Innapharma's software, programs, policies, procedures, methods, manuals,
materials, and related information developed prior to or during the
study shall remain the exclusive proprietary property of Innapharma
6. NexMed shall hold harmless and indemnify Innapharma, its agents and its
subcontractors as approved by NexMed from all liabilities and cost
(including reasonable attorneys' fees) arising out of or relating to
Innapharma's or said agents' or subcontractors' performance of contracted
services under this Agreement including liability for adverse experiences
to subjects in the study, except to the degree such liabilities or costs
are caused by the fault or negligence of Innapharma or said agents or
subcontractors. For the purpose of this section, "Subcontractor" and
"Agents" shall be defined to mean any third party which provides services
in support of the study including, but not limited to Printing Services,
Local IRBs, clinical research associates and clinical investigators.
7. The estimated budget for this study is set forth in Exhibit "B" attached
hereto and entitled "Budget Estimate". NexMed will make payments in
accordance with the attached Exhibit "C" entitled "Schedule of Payments".
8. Innapharma may terminate this agreement on thirty (30) days written
notice if NexMed materially breaches this agreement; provided, however,
that NexMed shall have the right to cure such breach within thirty (30)
days after receipt of such written notice of Innapharma's intention to
terminate.
NexMed may terminate this agreement on thirty (30) days written notice
with or without cause. In the event of termination by NexMed for reasons
other than default by Innapharma actions or recommendations of the MOH or
other involving regulatory authorities, NexMed's liability shall include
the total study budget amount listed in Exhibit B, with the only
exception, the unearned portion of the Investigator grant agreement up to
the date of receipt of termination notice, and all additional costs
associated with the termination itself.
In the event that the termination of the study is due to default by
Innapharma, NexMed's liability shall be limited to all sums owed to
Innapharma but unpaid for work performed to date of receipt of
termination notice as described in paragraph above.
In the event that the termination of the study is due to actions or
recommendations of the MOH or other involving regulatory authorities,
NexMed's liability shall be limited to all sums owed to Innapharma but
unpaid for work performed to date of receipt of termination notice and
all costs associated with termination itself, such as for the close-out
of study sites, completion of the database, etc., as described in the
two paragraphs above.
In the event of termination requiring close-out, Innapharma shall use its
best efforts to terminate all arrangements with investigators and other
obligations, as soon as possible, to avoid additional expenses.
2
9. This Agreement shall take effect upon execution by both parties and
shall continue until all obligations of the parties are completed unless
previously terminated. Sections 4, 5, 6, 7 and 8 shall survive
termination of this Agreement.
10. The parties acknowledge that NexMed is relying on the expertise of
Innapharma both for the conduct of the study and also for not exceeding
the budget set forth in Exhibit "C". Innapharma warrants and represents
that it will maintain strict budgetary controls and that it will not
exceed any of the itemized costs or the total study cost figure
contained in Exhibit "C" without the written approval of NexMed.
The parties shall review, on a monthly basis, actual Direct and Indirect
("Pass Through") costs associated with the ongoing performance of the
clinical trial. As necessary the parties shall make reasonable
adjustments to the budget, the payment schedule, the scope of the work,
and to this contract so as to insure that the study is adequately funded
and to promote the best interests of the clinical trial. All changes in
the scope or budget will require the written authorization of NexMed
prior to the commitment of any Innapharma resources.
The final payment (Exhibit D) will be made upon NexMed's acknowledgment
that the data included in the final data transfer are complete and
acceptable, and it is agreed that the format meets with NexMed's prior
specifications. This acknowledgment shall take place within 30 days of
receipt of the final data transfer. After acceptance of the final data
transfer, actual project costs incurred and payments made shall be
reconciled. Any outstanding balance as there may be after final
reconciliation shall be paid within thirty (30) days.
11. The parties stipulate and agree that 30 subjects shall be screened and
that 20 patients shall be enrolled and approximately 1 Investigator site
shall participate in this clinical trial.
12. Any change or modifications to this Agreement shall be in writing and
approved by Xxxx X. Xxxxx, Ph.D, for Innapharma and X. Xxxxxx Mo, Ph.D.
for NexMed or by their designees.
13. Any required notices shall be provided in writing, certified mail,
return receipt requested to the following individuals:
If to Innapharma:
Xxxx X. Xxxxx, Ph.D
President
Innapharma, Inc.
00 Xxxxxxxxxxxx Xxxx
Xxxxx Xxxxxx Xxxxx, XX 00000
3
If to NexMed:
X. Xxxxxx Mo, Ph.D
NexMed, Inc.
President
0000 Xxxxxxxx Xxxxx
Xxxxxxxx, XX 00000
14. The transfer of obligations from NexMed as Sponsor to Innapharma as
Contract Research Organization as required by the US Code of Federal
Regulations Section 21-312.52 is described in detail in Scope of Work
Section (Exhibit A).
This Agreement is not assignable and the obligations hereunder cannot be
delegated in whole or in part without the prior written consent of
NexMed. Innapharma will be an independent contractor and not an employee
of NexMed.
15. With respect to this contract and this study only, Innapharma agrees not
to use or imply the NexMed name or logo for advertising, promotional
purposes, raising capital, recommending investments, or in any way that
implies endorsement by NexMed. NexMed or Innapharma may publicly
disclose, in a news context, the fact that an Agreement has been entered
into, including the name of NexMed or Innapharma and the general nature
of the project covered by this Agreement. The party seeking such public
disclosure shall advise and provide the other party with a copy of the
proposed release and obtain proper written approval of said release.
16. No party will be liable for failure or delay in performing the
obligations set forth in this Agreement if such failure or delay is due
to any causes beyond the reasonable control of such party.
17. This Agreement shall be governed by the laws of the State of New Jersey.
4
CONTRACT SIGNATURE PAGE
NexMed, Inc.
By: /S/ Xxxxxx Xxx
------------------------
Xxxxxx Xxx
Vice President
Date: 10/30/96
Innapharma, Inc.
By: /S/ Xxxx X. Xxxxx
------------------------
Xxxx X. Xxxxx, Ph.D.
President
Date: 10/24/96
5
EXHIBIT A
Scope of Work for
HERPES MEDICAL DEVICE STUDY
EXECUTIVE SUMMARY
NexMed, Inc. has requested that INNAPHARMA provide a contract agreement and
budget encompassing management of all activities required to initiate and
complete a 20 patient pilot study in China including monitoring through final
statistical report in conjunction with NexMed's herpes medical device.
INNAPHARMA has prepared this contract agreement in two parts which allows
NexMed to proceed with several GO- NO/GO decision points while incurring only
minimal costs. An outline of the scope of work has been provided and the
project timeline and cost estimates follow in Exhibits E, B and D
respectively.
The first part of obtaining Clinical Trial Registration in China (permission
to conduct the trial) involves the information gathering and clinical
strategy development stage. Innapharma will assist NexMed in obtaining an
expert in China in the area of Herpes and medical devices. Innapharma will
schedule a meeting with the Ministry of Health. Innapharma and the Chinese
medical expert will pre-assess the proper approval pathway for the herpes
medical device in China. Innapharma will prepare a feasibility report based
on information obtained from China allowing NexMed to make educated Go -No/Go
decision.
The costs for this stage are included in the Clinical Registration costs
listed in the budget (Exhibit B), and include the identification of a Chinese
Medical Expert as well as a meeting with the Minister of Health.
CONCEPT SUMMARY
INNAPHARMA CONTACT
Primary Liaison: Xxxxxx Xxxxxx
Sr. Dir. Worldwide Clinical Operations
Phone: 000-000-0000 Ext. 652
Fax: 000-000-0000
6
PROTOCOL INFORMATION
Objective: To confirm safety and efficacy of NexMed's Medical
device used in the treatment of Herpes lip sores.
Design: Double blinded, single center pilot study
Patients: Twenty (20)
Expected 1 week
enrollment
period:
Total study 5 months
duration:
Number of sites: 1 site
Key inclusion History of herpes lip sores
criteria: On screening exposure to UV light, subject must
produce at least one eruption of a herpes lip lesion
within 7 day follow-up period
Subject must sign informed consent and agree to
potentially 2 exposures to UV light to the lip, and to
return to the clinic daily for 7 days post each
exposure (14 visits)
Key exclusion Documented history of ultra sensitivity to UV light
criteria:
Known alcohol or drug abuse
Subjects who are unwilling to return for all follow-up
visits
7
Scope of Work (cont'd)
I. CLINICAL TRIAL REGISTRATION--CHINA
This is the process of assembling, summarizing and translating all
pre-clinical and clinical information relating to work that has been
completed with the device to date by NexMed as well as any related devices
on the market in the US or in China. The strategy will be to equate this
herpes device with already marketed TENS devices which will make the
clinical registration process much easier and quicker.
Innapharma China will then submit this package to the Ministry of Public
Health. Upon review of this package, the Ministry will issue Clinical Trial
Registration Approval allowing the trial to begin or advise us as to the
proper pathway.
The assumption has been made that this clinical trial will be conducted
under U.S. Good Clinical Practice conditions and the data from the trial
will be submitable worldwide to augment other submissions
II. PREPARATION OF STUDY MATERIALS
INNAPHARMA assumes that there will be further modifications to the protocol
submitted to the Chinese regulatory authorities. Innapharma will work with
the Chinese regulatory authorities to produce a final Protocol that
satisfies all parties. Innapharma will develop and design the case report
forms (annotated in Chinese). It has been assumed that the Actual herpes
device as well as the "inactive device" (placebo) will be produced,
packaged and shipped to investigative sites by NexMed.
III. INITIATION OF STUDY
Innapharma will work with the Ministry of Health to select the most
qualified and experienced investigative sites for this study. Innapharma
will negotiate all investigator grants and provide a duly constituted local
IRB. Innapharma will conduct pre-study qualification visits to all sites.
Upon satisfactory approval each site will be shipped a pre-study package of
documents to prepare and submit to Innapharma as per GCP.
8
INITIATION VISITS/SITE COORDINATOR TRAINING
During the initiation visits study coordination training sessions to review
protocol / CRFs will be developed and conducted by INNAPHARMA personnel at
study initiation visits for all investigative sites involved in the
clinical trial.
IV. CONDUCT OF STUDY
PATIENT GRANTS
Innapharma will manage grant payments to all investigators.
STUDY MONITORING
INNAPHARMA will select study monitors from the Innapharma China Monitor
Network. All monitors are medical doctors. Monitors will be chosen based
on therapeutic experience as well as location. INNAPHARMA will utilize a
local Medical Monitor whenever possible to minimize travel time and costs.
ONGOING REPORTS
SERIOUS ADVERSE EVENTS
Serious adverse event reports will be forwarded to the sponsor within 24
hours of receipt by INNAPHARMA. INNAPHARMA will work with the investigative
site to gather any additional detail on serious adverse events required.
Adverse events (serious or non-serious) will be coded, tracked and reported
to the sponsor.
PROJECT MANAGEMENT
A dedicated project manager will be assigned to this project. The project
manager will coordinate the project team, track timelines, and monitor
financial activities. The project manager works in cooperation with the
project team to ensure timelines of the study are met and ongoing
communications with NexMed are maintained. Monthly status reports will be
provided to provide the following information:
1. Subject enrollment
2. Serious Adverse Events log
9
V. DATA MANAGEMENT
DATA COLLECTION
Data fields consisting of subject demographic, medical history, physical
exam, adverse events, and laboratory data will be collected on NexMed
CRFs for each subject. In addition, the efficacy data collected for
subjects will be entered into a data base.
DATA ENTRY
Prior to data entry, all CRFs will be coded and reviewed for completion.
Coding of data will utilize the WHO dictionary unless otherwise specified
by NexMed. All data will be double-key entered and checked against the
designated ranges. It is anticipated that 8 unique CRFs (of an estimated 32
total CRF's) will be processed per subject.
Computerized edit checks will be performed on the data on an ongoing basis.
Tracking spreadsheets will be created to account for all data collection
documents received and keyed by Data Entry.
DATABASE PROGRAMMING AND STARTUP
Based on the CRF design, a database design will be developed and
programmed. INNAPHARMA will create the trial database using customized
range checks for flagging data outliners for review, and process the data
utilizing documented coding guidelines.
TABLES, LISTINGS, AND PROFILES
Final table formats, listings, and profiles will be developed in
collaboration with NexMed. All table programming will be validated and
checked prior to final reports.
VI. STATISTICS
INNAPHARMA will perform the statistical analyses for the clinical trial as
per the final protocol analysis plan.
VII. EDITORIAL SERVICES
INNAPHARMA will produce a final study report including all statistical
tables suitable for customization and finalization by NexMed.
10
VIII. PROJECT TIMELINES
See attached schedule (Exhibit E)
IX. BUDGETS
See attached schedule (Exhibit B)
Proposed payment schedule (Exhibit C)
Investigator grant estimate (Exhibit D)
11
BUDGET ESTIMATE
EXHIBIT B
Duration of project (in months):...................................... 5
Duration of clinical trial (enrollment & study time).................. 4
Number of sites:...................................................... 1
Number of patients:................................................... 20
Cost per patient:..................................................... 112
# of payments to investigator:........................................ 2
Number of CRF's:...................................................... 32
Number of unique CRF's:............................................... 8
Number of patient diary cards
Investigator's / CRA Meeting:
number of investigators/coordinators:............................... 2
number of CRA's:.................................................... 2
number of Innapharma employees:..................................... 2
CRA's Conference Call:
number of investigators/coordinators:............................... 0
number of CRA's:.................................................... 0
number of Innapharma employees:..................................... 0
Number of monitoring visits: (do not include Initiation Visit)........ 4
IRB:
Local IRB--number of sites.......................................... 1
Central IRB--number of sites........................................ 0
Project Management: (estimated number of hrs per week)................ 10
# of investigator's newsletters:...................................... 2
# of data transfers to sponsors....................................... 2
Sponsors Name: NEXMED, INC. (Herpes device)
12
BUDGET ESTIMATE
EXHIBIT B
TASK NAME INNAPHARMA COST RESPONSIBILITY
--------------------------------------------------------------------------------- ---------------- -------------------
Preparation of Study Materials
Information acquisition/Medical expert/China Mtg................................. x
Clinical Trial Registration Process.............................................. 10,000
Protocol development/assembly/shipping........................................... 800
CRF development.................................................................. 1,200
clinical supplies--shipping.................................................... x
Total:........................... $ 12,000
Initiation of Study
recruit investigator's........................................................... 40
negotiate grants with investigator's............................................. 40
payments to investigator's....................................................... 20
Local IRB........................................................................ 200
prestudy visit--CRA time......................................................... 60
prestudy visit--CRA expenses..................................................... 350
pre-study documents.............................................................. 60
initiation visit--CRA time....................................................... 100
initiation visit--CRA expenses................................................... 30
Total:........................... $ 900
Conduct of Study
investigator site grant.......................................................... 2,240
monitoring visits--CRA time...................................................... 400
monitoring visits--CRA expenses.................................................. 120
provide status reports -- monthly................................................ 400
SAE's reporting/follow up........................................................ 160
project management............................................................... 500
Total:........................... $ 3,820
Data Management
initial CRF/protocol review...................................................... 280
develop coding guidelines........................................................ 356
establish edit specs/query program/list.......................................... 35
design/set-up database, including labs, diaries.................................. 680
program data edit checks......................................................... 680
database validation/100% check on fields......................................... 345
logging in of CRF's.............................................................. 160
CRF coding....................................................................... 240
encoding of AE's, con meds, etc.................................................. 200
single data entry................................................................ 240
double data entry................................................................ 240
13
BUDGET ESTIMATE
EXHIBIT B
TASK NAME INNAPHARMA COST RESPONSIBILITY
--------------------------------------------------------------------------------- ---------------- -------------------
double key comparison check...................................................... 160
upload/integration CRF data file................................................. x
fax/or e-mail transfer of first 50 pts to USA.................................... 800
track data entry/queries/resolution.............................................. 56
generate queries................................................................. 45
resolve queries.................................................................. 45
perform QC on 100% of CRF's (key variables)...................................... 234
program custom listings, summaries, profiles..................................... 235
generate listings................................................................ 40
review listings.................................................................. 245
transfer data to sponsor......................................................... 125
Total:........................... $ 5,441
Statistical Analysis
prepare mock tables.............................................................. 200
program SAS datasets............................................................. 150
perform statistical analysis..................................................... 1,500
write statistical report......................................................... 450
Total:........................... $ 2,300
Medical Writing
integrated study report.......................................................... x
journal article.................................................................. x
poster sessions.................................................................. x
Investigator's brochure.......................................................... x
Total:........................... $ 0
Grand Total:........................... $ 24,461
14
EXHIBIT C
HERPES DEVICE STUDY
PROPOSED PAYMENT SCHEDULE
PAYMENT # MILESTONE ESTIM. DATE AMOUNT
------------------- ----------------------------- ------------- ------------
1 Contract finalization 11/1/96 $ 4,461.00
2 Clinical trial approval 12/15/96 $ 5,000.00
3 First patient in 12/31/96 $ 5,000.00
4 Last patient out 1/29/97 $ 5,000.00
5 Final report 3/13/97 $ 5,000.00
TOTAL $24,461.00
15
EXHIBIT D
Investigator Grant Estimate
HERPES DEVICE STUDY
(20 PATIENT PILOT STUDY)
SCREENING PHASE
Visit 1............................................................ $ 20.00
Brief history and physical
Inclusion/exclusion criteria review
Informed consent
UV exposure
Visit 2-7
Day 2-7 follow-up visits ($5.00 x 6 visits)............. $ 30.00
CRF Completion
Assessment of herpes lesion
Culture of herpes lesion
Adverse event queries
--------------------------------------------
TREATMENT PHASE
Visit 8
UV exposure
In-house observation 4-8 hours
Treatment with device
Culture
Visits 9-14
Day 9-14 follow-up visits ($5.00 x 6 visits)............ $ 30.00
CRF Completion
Assessment of herpes lesion
Culture of herpes lesion
Adverse event queries
Patient stipend (transportation expenses to participate in
trial)........................................................... $ 10.00
Administrative overhead............................................ $ 22.00
------------------------------------------------------------------------------------
TOTAL.............. $ 112.00
$112.00/patient x 20 Patients = $2,240.00
16
EXHIBIT E
NexMed Herpes Medical Device
China Study Timeline
ID TASK NAME DURATION START FINISH
--------- -------------------------------------------------------------------------- ------------- --------- ---------
1 PRELIMINARY MEETINGS/CONTRACT 65d 9/5/96 12/4/96
2 Initial meeting NexMed / Innapharma 0d 9/5/96 9/5/96
3 Bid proposal sent 0d 9/20/96 9/20/96
4 Contract agreement signed 5d 10/23/96 10/29/96
5 CLINICAL REGISTRATION PROCESS 55d 9/19/96 12/4/96
6 Strategy development 14d 10/30/96 11/18/96
7 Medical expert identified 10d 10/30/96 11/12/96
8 Meeting with Minister of Health 1d 11/13/96 11/13/96
9 Clinical strategy approved by MOH 3d 11/14/96 11/18/96
10 NexMed's GO/NO GO DECISION 0d 11/18/96 11/18/96
11 Clinical trial registration 55d 9/19/96 12/4/96
12 Assembly of all NexMed data 10d 9/19/96 10/2/96
13 Assembly of all literature to date 10d 10/3/96 10/16/96
14 Finalization of Clin. Reg. Package 5d 10/17/96 10/23/96
15 Translation of Package to Chinese 10d 10/24/96 11/6/96
16 Submission to MOH 0d 11/6/96 11/6/96
17 Approval of Clinical Registration 20d 11/7/96 12/4/96
18 CLINICAL TRIAL 74d 12/5/96 3/18/97
19 site / investigation selection 2d 12/5/96 12/6/96
20 Pre-study evaluation visit 1d 12/9/96 12/9/96
21 Case Report form development 10d 12/10/96 12/23/96
22 IRB selection 3d 12/24/96 12/26/96
23 Study initiation visit 1d 12/27/96 12/27/96
24 Enrollment and treatment time 21d 12/30/96 1/27/97
25 Clinical trial complete 1d 1/28/97 1/28/97
26 Data entry complete / data base clean 15d 1/29/97 2/18/97
27 Statistical analysis 15d 2/19/97 3/11/97
28 Final report sent to NexMed 5d 3/12/97 3/18/97
------------------------
Project:
Date: 10/24/96
17
AMENDMENT
VIRATROL-TM- HERPES DEVICE STUDY
The following documents, incorporated by reference herein, amend to contract
for the VIRATROL-TM- Herpes Device Study.
Exhibit A.1--Concept Summary
Exhibit B.1--Budget Estimate
Exhibit C.1--Payment Schedule
All other terms and conditions of the original agreement remain in force,
except as amended herein.
IN WITNESS WHEREOF, the parties have caused this Agreement to be duly
executed by an appropriate officer as of the day and year first above written.
NexMed, Inc. Date: 2/13/97
By: /S/ Xxxxxx Xxx
--------------------------
Xxxxxx Xxx
Vice President
Innapharma, Inc.
By: /S/ Xxxxxx X. Xxxxxx Date: 2/4/97
-------------------------
Xxxxxx X. Xxxxxx
Corporate Vice President
Clinical & Nonclinical Operations
18
EXHIBIT A.1
CONTRACT AMENDMENT
MODIFIED CONCEPT SUMMARY
As a result our recent trip to China and ongoing protocol discussions, it
was agreed that scope of work as outlined in the contract had to be modified. It
will be necessary to include suggestions from Chinese medical doctors and the
Ministry of Health. They suggested conducting an unblinded prestudy with 10
subjects to provide the physician an opportunity to become familiar with the
ViratroI-TM- device before conducting the larger blinded trial. It was
additionally suggested, that enrollment of blinded trial be increased to
approximately 60 subjects. For both studies, Innapharma will prepare the
protocol, case report forms, conduct an investigator meeting, monitor the trial
and prepare the final statistical report (summary only for the unblinded pilot
trial).
INNAPHARMA CONTACT
Primary liaison: Xxxxx Xxxxxx
Director Clinical Operations
Phone: (000) 000-0000 Ext. 647
Fax: (000) 000-0000
PROTOCOL INFORMATION FOR 10 SUBJECT UNBLINDED PILOT TRIAL
Objective: To give the investigator an opportunity to become familiar
with and assess the Viratrol-TM- device as used in the
treatment of Herpes Labialis.
Design: Unblinded single center pilot study
Patients: Ten (10)
Expected
enrollment
period: 3 weeks
Total study
duration: 1 month
Number of
sites: 2 sites
Key inclusion
criteria: History of herpes lip sores
Presence of active herpes libialis symptoms
Key exclusion
criteria: Known alcohol or drug abuse
Subjects who are unwilling to return for all follow-up
visits
19
BUDGET ESTIMATE
EXHIBIT B.1
Duration of project (in months):...................................... 5
Duration of clinical trial (enrollment & study time).................. 4
Number of sites:...................................................... 1
Number of patients:................................................... 60
Cost per patient:..................................................... 112
# of payments to investigator:........................................ 2
Number of CRF's:...................................................... 32
Number of unique CRF's:............................................... 8
Number of patient diary cards......................................... 0
investigator's/CRA Meeting:
number of investigators/coordinators:.............................. 0
number of CRA's:................................................... 0
number of innapharma employees:.................................... 0
CRA's Conference Call:
number of investigators/coordinators:.............................. 0
number of CRA's:................................................... 0
number of Innapharma employees:.................................... 0
Number of monitoring visits: (do not include Initiation Visit)........ 4
IRB:
Local IRB--number of sites......................................... 1
Central IRB--number of sites....................................... 0
Project Management: (estimated number of hrs per week)................ 2
# of investigator's newsletters:...................................... 0
# of data transfers to sponsors....................................... 2
Sponsors Name: NexMed
20
BUDGET ESTIMATE
EXHIBIT B.1
CLIENT'S
TASK NAME INNAPHARMA COST RESPONSIBILITY
--------------------------------------------------------------------------------- ---------------- -------------------
Preparation of Study Materials
clinical Trial Registration Process.............................................. 15,000
protocol development/assembly/shipping........................................... 800
CRF development.................................................................. 1,280
clinical supplies--shipping.................................................... x
Total:........................... $ 17,080
Initiation of Study
recruit investigator's........................................................... 40
negotiate grants with investigator's............................................. 40
payments to investigator's....................................................... 20
Local IRB........................................................................ 200
prestudy visit--CRA time......................................................... 60
prestudy visit--CRA expenses..................................................... 30
pre-study documents.............................................................. 20
initiation visit--CRA time....................................................... 100
initiation visit--CRA expenses................................................... 30
Total:........................... $ 540
Conduct of Study
investigator site grant.......................................................... 6,720
monitoring visits--CRA time...................................................... 400
monitoring visits--CRA expenses.................................................. 120
provide status reports--monthly................................................ 400
SAE's reporting/follow up........................................................ 480
project management............................................................... 1,600
Total:........................... $ 9,720
21
BUDGET ESTIMATE
EXHIBIT B.1
CLIENT'S
TASK NAME INNAPHARMA COST RESPONSIBILITY
--------------------------------------------------------------------------------- ---------------- -------------------
Data Management
initial CRF/protocol review...................................................... 280
develop coding guidelines........................................................ 356
establish edit specs/query program/list.......................................... 35
design/set-up database, including labs, diaries.................................. 680
program data edit checks......................................................... 680
database validation/100% check on fields......................................... 345
logging in of CRF's.............................................................. 480
CRF coding....................................................................... 720
encoding of AE's, con meds, etc.................................................. 600
single data entry................................................................ 720
double data entry................................................................ 720
double key comparison check...................................................... 480
fax/or e-mail transfer of first 50 pts to USA.................................... 800
track data entry/queries/resolution.............................................. 100
generate queries................................................................. 293
resolve queries.................................................................. 293
perform QC on 100% of CRF's (key variables)...................................... 624
program custom listings, summaries, profiles..................................... 235
generate listings................................................................ 40
review listings.................................................................. 640
transfer data to sponsor......................................................... 125
Total:........................... $ 9,245
Statistical Analysis
prepare mock tables.............................................................. 200
program SAS datasets............................................................. 150
perform statistical analysis..................................................... 1,500
write statistical report......................................................... 450
Total:........................... $ 2,300
Medical Writing
integrated study report.......................................................... X
journal article.................................................................. X
poster sessions.................................................................. X
Investigator's brochure.......................................................... X
Total:........................... $ 0 X
Grand Total:........................... $ 38,885
22
Exhibit C.1
Herpes Device Study
Herpes Device (Original Contract).................................. $ 24,461
Herpes Device (Revised Contract)................................... $ 38,885
Open Label Study:.................................................. $ 8,328
Total Amount:...................................................... $ 47,212
REVISED PAYMENT SCHEDULE
PAYMENT # MILESTONE ESTIMATED DATE AMOUNT
----------------- -------------------------------------------------------- -------------- ---------
1 Contract Finalization 11/1/96 $ 4,461
2 Clinical Trial Site Selection / Approval 12/15/96 $ 5,000
3 Final Protocol & CRFs 2/28/97 $ 17,000
4 First Patient In 3/14/97 $ 7,550
5 Last Patient Out 7/31/97 $ 7,550
6 Statistical Analysis 8/25/97 $ 5,650
Total: $ 47,212
23
AMENDMENT
No.2
VIRATROL-TM- HERPES DEVICE STUDY
The following documents, incorporated by reference herein, amend to contract
for the VIRATROL-TM- Herpes Device Study
Exhibit B.2--Budget Estimate
Exhibit C.2--Payment Schedule
All other terms and conditions of the original agreement remain in amended
herein.
IN WITNESS WHEREOF, the parties have caused this Agreement to by an
appropriate officer as of the day and year first written below.
NexMed, Inc. Date: 4/30/97
By: /S/ Xxxxxx Xxx
-------------------------------
Xxxxxx Xxx
Vice President
Innapharma, Inc. Date: 4/28/97
By: /S/ Xxxxxx X. Xxxxxx
-------------------------------
Xxxxxx X. Xxxxxx
Corporate Vice President
Clinical & Nonclinical Operations
24
BUDGET ESTIMATE
EXHIBIT B.2
Clinical report prepared for the open-label pilot study.
STATISTICAL ANALYSIS
DESCRIPTION COST
Prepare mock tables........................ $ 65
Program SAS datasets....................... $ 50
Perform statistical analysis............... $ 250
Write report............................... $ 500
TOTAL:............ $ 865
25
EXHIBIT C.2
Herpes Device Study
Herpes Device (Original Contract).................................. $ 24,461
Herpes Device (Revised Contract)................................... $ 38,885
Open Label Study:.................................................. $ 8,328
Clinical Report: Open Label Study.................................. $ 865
TOTAL AMOUNT:............... $ 48,077
REVISED PAYMENT SCHEDULE
ESTIMATED
PAYMENT # MILESTONE ESTIMATED REVISED DATE DATE AMOUNT
----------------- -------------------------------------------- -------------- --------- ---------
1 Contract Finalization 11/1/96 $ 4,461
2 Clinical Trial Site Selection/Approval 12/15/96 $ 5,000
3 Final Protocol & CRFs 2/28/97 $ 17,000
4 Clinical Report: Open Label Study 5/12/97 $ 865
5 First Patient In 3/14/97 6/30/97 $ 7,550
6 Last Patient Out 7/31/97 10/15/97 $ 7,550
7 Statistical Analysis 8/25/97 11/15/97 $ 5,650
TOTAL: $ 48,077
26
