**CONFIDENTIAL PORTIONS HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT AND HAVE BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION (THE COMMISSION).** TASK ORDER MEDPACE Task Order Number: 1 MEDPACE Project Number: ORINS07

 

1.

Scope of Work:  MEDPACE shall perform the services described in the Scope of Work, attached hereto as Appendix 1, in accordance with the Project Schedule, attached hereto as Appendix 2, and protocol version dated 14 August 2012.

 

2.

Compensation:  For performance of these Services, SPONSOR shall pay to MEDPACE an amount equal to the Project Budget set forth in Appendix 3, which amount shall be payable pursuant to the Payment Schedule set forth in Appendix 4.  The Project Budget is provided for cost analysis purposes.  It is agreed that all fees are fixed prices unless the underlying assumptions as written in Appendix # 1 SCOPE OF WORK, and Appendix #2, PROJECT SCHEDULE are changed, and all such changes shall be documented in a Contract Amendment.  After staff is assigned, costs are incurred based upon allocation of staff capacity.

 

3.

Third Parties/Vendors: MEDPACE is responsible for coordinating with the vendors which will be selected and approved by SPONSOR.  SPONSOR will review and comment on all Third Parties/Vendors contracts prior to MEDPACE’s execution of such contracts.

 

4.

Transfer of Obligations:  Sponsor Obligations transferred to MEDPACE by SPONSOR (consistent with the regulations set forth in 21 C.F.R. Section 312, Subpart D) are identified in Appendix 5.

 

5.

MSA. The provisions of the Master Services Agreement are hereby expressly incorporated by reference into and made a part of this Task Order.

Signature: 

By: 

John Wynne

Title: 

Executive Director

Business Development Support

By: 

Nadav Kidron

Title: 

CEO

Number of investigators per country

10 sites + 5 Back-up sites (United States)

Number of screened patients

294 patients

Number of randomized patients

147 patients

Duration of enrollment period (first patient in–last patient in)

4 months

Duration of screening/treatment/follow-up period

~7.5 weeks

Duration of Investigator Meeting

1 meeting (12-hour duration); location TBD

Location and duration of Kickoff Meeting

1 meeting at Medpace (8-hour duration)

Teleconferences

26 calls ( approx. 2 per month; one hour each)

Number of qualification visits

1 visit

Number of initiation visits

10 visits

Number of routine monitoring visits (RMV)

40 visits

Monitoring frequency

On average, every 5-6 weeks as needed

Number of close-out visits

Assumed part of final RMV

Number of serious adverse events (SAEs)

8 SAEs

Total CRFs

5880 CRFs

CRFs per patient

40 CRFs

Unique CRFs

18 CRFs

Average data points per CRF

12 data points

Number of raw listings

23 raw listings

Number of unique TFLs

25 unique TFLs

Number of version TFLs

25 version TFLs

Study conducted in compliance with SOPs and Policies

Medpace SOPs and Policies

X

Write protocol

X

Review protocol

Includes comment from Medpace team

X

Submit protocol amendments

X

Develop ICF template

Using Medpace template

X

Review ICF template

X

ICF amendments

1 amendment

X

ICF local customization

Negotiate changes with each site

X

CRF design

Design of CRFs and completion guidelines

X

X

Site identification

Medpace to identify qualified Investigators; Oramed to select/approve sites; assumes 15 sites selected (10 main sites + 5 back-up sites)

X

Investigator Meeting Planning

Arrange meeting

X

Preparation of Investigator Meeting(s)

Preparation and distribution of binders and meeting materials; includes presentation by Medpace associates

X

Investigator Meeting Attendees

CTM, Medical Expert, Project Coordinator, Data Manager, Statistical Analyst, Safety Manager, IVRS Manager and 3 CRAs; Assumes 1 day meeting

X

X

Investigator Meeting Planner Contract Negotiation and Payment Management

Medpace will negotiate the contract on behalf of Sponsor;  Sponsor will sign the contract and make payments to the meeting planner

X

Kickoff Meeting Attendees

CTM, Medical Expert, Project Coordinator, Project Assistant, Regulatory Submissions Manager, Data Manager, Statistical Analyst, Safety Manager, Safety Specialist and Lead CRA; Assumes 8 hrs. meeting at Medpace office

X

Submit essential documents to US central IRB

13 sites using central IRB (9 main + 4 back-up sites)

X

Support sites to submit essential documents to US local IRB

2 site using local IRB (1 main + 1 back-up sites)

X

Trial Master File set-up and maintenance

Set up and maintain file for all study sites according to Medpace SOPs

X

Clinical trial management

Provide overall study management for 10 sites

X

Project website

Medpace to develop secure, project-specific website containing relevant information and tools

X

Newsletters

6 monthly electronic newsletters

X

Ongoing essential document collection

Ongoing collection and maintenance of site-specific documents

X

Tracking of study medication shipments

Assumes 2 shipments per site for 10 sites

X

Supply, packaging, and labeling of study  medication

Assumes Medpace will contract and manage packaging, labeling and drug depot vendor

X

Storage and distribution of

Study medication

Assumes Medpace will contract and manage vendor to perform packaging, labeling and drug depot services

X

X

Destruction of study medication

Assumes Medpace will contract and manage drug depot vendor who will destroy drug upon Sponsor approval

X

Study medication accountability procedures

Follow Medpace SOPs and approved by Sponsor

X

Site contract negotiation

Negotiate site contract and budget for 15 sites

X

Investigator payments management

Make 2 quarterly payments per site for 10 sites

X

X

External vendors contract negotiation and management

Assumes Medpace will contract and manage drug depot vendor; Medpace will coordinate the purchase and distribution of  CGM devices and study supplies upon sponsor approval

X

Central lab selection

Please reference MRL budget

X

Central lab contract negotiation and management

 MRL

X

Central IRB payment management

Assumes 1 central IRB and 2 quarterly payments

X

Clinical Research Associates (CRAs)

3 CRAs

X

Qualification visits

1 visit, 4 hrs. on-site; Cost of $2,347 shall be charged for each additional visit

X

Monitoring plan

Ongoing updates

Includes monthly meetings

X

Site initiation visits

10 visits, 4 hrs. on-site; Cost of $2,347 shall be charged for each additional visit

X

Routine monitoring visits (RMVs)

40 visits

X

Frequency of RMVs

On average, every 5-6 weeks, as needed

X

Estimated on-site time

16 hours

X

Close-out visits

Assumed combined with final RMV

X

In-house monitoring coordination

Medpace CRA contact sites to discuss project-specific issues; records maintained in ClinTrak

X

Medical monitoring

Medical Expert on-call 24/7 during recruitment and treatment periods for 10 sites

X

Develop Safety Monitoring Plan

Includes one final version and one revision. Assumes utilization of Medpace SOPs

X

SAE reporting

All SAEs will be reported by sites to Medpace. Includes one initial and two follow-up reports per case; Assumes 8 SAEs; Cost of $1,339 shall be charged for each additional unit

X

Development of safety database

ARGUS will be used; Medpace to hold database

X

Enter SAEs into safety database

8 SAEs

X

Medical monitor review of SAE reports

Includes assessment of expectedness and company causality

X

Receive, query, and follow-up on reported SAEs

X

Generate SAE narratives

Narratives written Clinical Study Report ready. Assumes final approval by Medpace Medical Monitor prior to distribution to sponsor.

X

Generate expedited SAE reports safety report

Assumes 1 expedited report, if additional events occur, a unit cost of $1,636 per report  shall be charged.

X

X

Distribute expedited SAE reports to FDA

Oramed to review and approve prior to submission

X

Distribute expedited SAE reports to central IRB

Compile and submit documents

X

Preparation of safety notification letters

Sponsor to review and approve prior to submission

X

Distribute safety notification letter for this protocol to sites

10 sites

 

X

 

Prepare periodic reports for regulatory authorities

X

X

Prepare  Annual Safety Report

Medpace to prepare safety line listings to be included in IND Annual Report;  Oramed will be responsible for IND Annual Report filing

X

Distribute periodic reports to regulatory authorities/ECs

X

Distribute  Annual Safety Report to regulatory authorities/ECs

Assumes Oramed will be responsible for IND Annual Report

X

Ongoing reconciliation between clinical and safety database

A final reconciliation is completed prior to database lock

 

 

 

X

 

Ongoing clinical trial AE data review including signal detection and trend analysis

Required per FDA guidance

X

Write narratives for withdrawals due to AE and/or abnormal lab values for inclusion in clinical study report

Assumes 1 withdrawal due to AE. If additional events occur, a unit cost of $915 shall be charged.

X

Randomization/Drug Supply Management

Provide study-specific system for randomization, patient visit tracking, and customized reports, drug management (via web or phone 24/7), including maintenance and Help Desk. Assumes English language only.

 

 

 

 

X

Develop data management (DM) documents

DM documents include:

- Database specifications;

- Guidelines for the tracking of CRFs and data queries;

- Guidelines for entry of the CRF data; and

- Database edit check specifications

X

Database development

EDC system,  ClinTrak EDC

X

Database validation

Medpace SOPs

X

EDC Help Desk

Medpace provide support via phone/email

X

DM coordination and status reporting

Medpace coordination includes:

- CRF tracking

- Data cleaning/editing

- Query tracking

Medpace monthly DM status reports provided via secure website include:

- CRF status by site

- Patient status by site

- Query status by site

X

Query tracking/resolution

X

Coding of AE/concomitant medications/medical histories

Assumed that Sponsor holds a valid agreement with the Maintenance and Support Services Organization (MSSO) for the MedDRA dictionary and Uppsala Monitoring Centre (UMC) for the WHODrug dictionary

X

Number of AE codes

5 AE codes per patient

X

Number of concomitant medications

5 concomitant medications per patient

X

Number of medical histories/conditions

X

Number of external data sources

Assumes MRL

X

Data transfers from external data sources

2 quarterly transfers from MRL

X

Data transfers to Sponsor

2 transfers (1 test, 1 final)

X

Deliver data

CDISC SDTM

X

Database document

Medpace submission-ready

X

Develop Statistical Analysis Plan (SAP)

Medpace format and template; Medpace to prepare the SAP to be included in the IND filing. The SAP will be revised (if needed) and finalized prior to the Database Lock.  

X

Programming, validation, and generation of Tables, Figures, Listings (TFLs)

23 raw listings

25 unique TFLs

25 version TFLs

2 derived datasets

X

Results review meeting

One meeting via teleconference after delivery of analysis results

X

Study report shell (SRS)

SRS incorporates protocol-related and statistical methodology information and in-text table shells in the results sections

X

SRS review

X

Pre-final study report (PFSR)

PFSR is a complete version of the report, including results, but without the appendices

X

PFSR review

X

Final study report (FSR)

FSR is a complete version of the report including appendices.

X

 

Publishing FSR

FSR file is converted to an Adobe PDF file and published by setting applicable document attributes.

X

Bookmarking/

hyperlinking FSR

Apply internal and external navigation via bookmarking/hyper linking from the FSR to any corresponding appendices

Medpace Begins Work*

SEP-2012

Final Protocol

SEP-2012

Statistical Analysis Plan (Final Draft for IND Filing)**

15-NOV-2012

First Patient, First Visit

31-JAN-2013

Last Patient, First Visit

02-JUN-2013

Last Patient, Last Visit

25-JUL-2013

Final Database Lock

+ 6 weeks

Final Tables, Figures, and Listings available

+4 weeks

Delivery of Final Clinical Study Report

+ 8 weeks

Medpace Ends Work

NOV-2013

Start-up Services                Review Protocol

Protocol

1

**THE CONFIDENTIAL PORTION HAS BEEN SO OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT AND HAS BEEN FILED SEPARATELY WITH THE COMMISSION.**

  CRF Review/Development

CRF Book

1

  Investigator Meeting

Meeting

1

  Kick-Off Meeting

Meeting

1

  Project Specific Training

Study

1

  Vendor Contract Negotiation

Vendor

1

  Investigator Contract Negotiation

Site

1

  Site Identification/Selection

Site

15

  Investigator File Set-up

Study

1

  Initial Essential Document Collection

  Total

Site

15

Meetings                                 Conference Calls

  Total

Call

26

Interactive Voice Response  IVRS Development

System (IVRS)

System

1

  IVRS Maintenance and Help Desk

Months

5.8

  IVRS System Utilization and Hosting

  Total

Months

5.8

Project Management          Project Management

Months

5.8

  Vendor Management

Months

5.8

  Newsletters

Edition

6

  Ongoing Essential Document Collection and Review

Months

5.8

  ICF Amendment

Amendments

1

  Vendor Payment Administration

Payment

6

  Investigator Grants Management Total

Site Payments

20

Clinical Safety                     Medical Monitoring

Months

5.8

  Safety Plan Development

Plan

1

  SAE Reporting

Events

8

  Processing Expedited SAE Reports

Events

1

  Other Narrative Preparation Total

Events

1

Clinical Monitoring                Monitoring Plan Development

  and Ongoing Maintenance

Months

5.8

  Pre-Study Visits

Visits

1

  Study Initiation Visits

Visits

10

  Site Management

Site Month

58.1

  Routine Monitoring Visits Total

Visits

40

Data Management                   Data Management Manual

Study

1

**THE CONFIDENTIAL PORTION HAS BEEN SO OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT AND HAS BEEN FILED SEPARATELY WITH THE COMMISSION.**

Database Development

Database

1

Database Conversion (CDISC)

Database

1

EDC User Acceptance Testing

UAT

1

Data Entry and Cleaning

CRF Book

5880

EDC Help Desk

Site Months

58.1

DM Coordination and Status Reports

Months

5.8

    EDC System Utilization and Hosting

    Total

Months

5.8

Biostatistics                          Analysis Plan

Ran

1

Analysis Programming and Generation

Analysis

1

Raw Data Listings

Raw Listings

23

Unique TLFs

Unique TFL

25

Version TLFs Total

Version TFL

25

Medical Writing                       Clinical Study Report

    Total

Study Report

1

Pre-Funded Expenses          Investigator Payments

Randomized Patients

147

**THE CONFIDENTIAL PORTION HAS BEEN SO OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT AND HAS BEEN FILED SEPARATELY WITH THE COMMISSION.**

    Drug Packaging, labeling and Depot Fees

Study

1

    Central Laboratory Fees (MRL)

Study

1

    Study Specific Supplies (CGM & Supplies)

Study

1

    CGM Data Management Software (SweetSpot)

System

1

Pass-Through Costs           Monitoring Tray el

Visit

51

**THE CONFIDENTIAL PORTION HAS BEEN SO OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT AND HAS BEEN FILED SEPARATELY WITH THE COMMISSION.**

   Central IRB Fees

Study

1

   Telecommunication Fees

Calls

26

   Misc. Printing/Copying/Shipping

Sites

10

   Meeting Expense

Study

1

Sponsor Directly Paid Vendor   Investigator Meeting Planner

Fee

Meetings

1

**THE CONFIDENTIAL PORTION HAS BEEN SO OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT AND HAS BEEN FILED SEPARATELY WITH THE COMMISSION.**

1

Task Order Signed

Sep-12

$           63,362

5.0%

2

Kick-Off Meeting

11/5/2012

$        139,397

11.0%

3

Investigator  Meeting

1/3/2013

$          76,035

6.0%

4

First Patient Screened

1/31/2013

$        190,087

15.0%

5

25% Patients Enrolled

3/16/2013

$        190,087

15.0%

6

50% Patients Enrolled

4/18/2013

$        190,087

15.0%

7

Last Patient Screened

6/2/2013

$        164,742

13.0%

8

Last Patient Complete

7/25/2013

$        126,725

10.0%

9

Submission of Clinical Study Report to Sponsor for Final Approval

11/30/2013

$        126,725

10.0%

     Total Payments:

 $  1,267,246

100%

b/w print, 20-24 lb.

0.15

total sheets, includes all impressions, sizes, or cuts

color print, 20-24 lb.

0.20

total sheets, includes all impressions, sizes, or cuts

b/w print, 28-60 lb.

0.20

total sheets, includes all impressions, sizes, or cuts

color print, 28-60 lb.

0.25

total sheets, includes all impressions, sizes, or cuts

b/w waterproof

1.05

total sheets, includes all impressions, sizes, or cuts

color waterproof

1.10

total sheets, includes all impressions, sizes, or cuts

tabs 5-bank

3.00

laminating pouches

0.95+

Plus cost of color or b/w print

card/cover stock

0.30

color only

folder

0.50

2-pocket, usually includes label

binder 1"

8.00

includes front cover and spine

binder 1.5"

10.00

includes front cover and spine

binder 3"

15.00

includes front cover and spine

plastic coil binding 1/4"

0.75

plastic coil binding 3/8"

1.10

plastic coil binding 1/2"

1.50

plastic coil binding 1"

3.00

CDs

0.28

per CD

CD labels

0.18

per label

Mobile communication and data standard daily rate

cost per day while CRA is traveling

Other internet charges by use (receipt required)

Drug:

ORMD-0801

Study ID:

 ORINS07

Study Title:

Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Pharmacodynamics of Multiple Oral Bedtime Doses of ORMD-0801 (Insulin Capsules) in Adult Patients with Type 2 Diabetes Mellitus who are Inadequately Controlled with Diet and Metformin

CRO Name:

Medpace, Inc.

CRO Address:

5375 Medpace Way, Cincinnati, OH 45227

Obligations Transferred to Medpace: R the Appropriate Box(es).

 o All obligations in 21 CFR 312, Subpart D (Responsibilities of Sponsors) have been transferred to Medpace.

 x The following obligations have been transferred to Medpace:

x (a) Maintain adequate records showing investigational drug receipt, shipment, or other disposition.

o (b) Maintain complete and accurate records showing any financial interests of the investigator subject to 21 CFR 54.

o (c) Retain the records and reports required by the regulations for 2 years after the marketing application is approved, or if not approved, until 2 years after investigational drug shipment is discontinued and FDA has been notified.

o (d) Retain reserve samples of any test article and reference standard identified and used in bioequivalence or bioavailability studies.

x (a) Permit FDA personnel to have access to and copy and verify any records and reports related to the clinical investigation.

o (b) Permit DEA personnel to have access to and copy records related to the shipment, delivery, receipt and disposition of any investigational controlled substance.  Assure adequate storage precautions are taken for investigational new drug substances listed in any schedule of the Controlled Substances Act.

o Assure the return (or alternate disposition) of all unused supplies of the investigational drug from each discontinued/terminated investigator; maintain written records of any disposition of the investigational drug.

(a)   Other

o Please describe any other applicable transfers below: