VADODARA ETHICS COMMITTEERace Course Medical Centre, Race Course Tower

Vadodara- 390007, IndiaV EC I

APPROVAL OF NEW PROJECT

Date: 29/02/12To,Dr. Arran Khanna,Principal Investigator.Sun Pharmaceutical Industries Ltd.Baroda. India

The meeting of Vadodara Ethics Committee, Vadodara was held on 16/02/12 and28/02/2012 with Dr. R. V. Bhatt as the Chairperson.

Followin g members of VEC were present:Name Qualification DesignationDr. R.V.Bhatt M.D. (Obs. & Gyn.) Consulting Obstetrician & Gynaecologist.

Dr. G.N.Vaishnav M.D. (Gen. Med.) Consulting Physician

Dr. Vipul Desai M.D. (Gen. Med.) Consulting Physician

Mr. Atul Mehta B.A., L.L.B Advocate

Dr. B.P. Udwadia M.D. (Pharmacology) Scientist

Dr. Ashish Sethi MD, DM (PGI) Gastroenterologist

Dr. Vikas Ponda M.D.(Psychiatry) Consulting Psychiatrist

Mrs. Sangita Patel B.Sc. (Zoology) Member Secretary Social Scientist,/ Lay-peson

Mrs. Snehal Bhatt M.S.W. Social Scientist/ Lay-person

Dr. Darshak Shah M.S. (Gen. Sur.) Consulting general surgeon

The Vadodara Ethics Committee reviewed and discussed your application toconduct the clinical project entitled "A Randomized, Double-Blind, Active-Controlled, Cross Over, Single Dose Study To Assess The Safety, Tolerability AndPharmacokinctics Of Enteric Coated Compound B09 In Healthy Male Subjects'' on 16thFebruary, 2012 and 28 th February, 2012.

Meeting minutes:

Date: 16-02-12Dr. Udwadia and Dr. G.N.Vaishnav presented protocol.

1309 is a new chemical entity, a pro-drug of Baclofen. VEC offers its views on theprotocol CI.R ._09 04 as follows.The protocol needs some clarifications/justification/changes for this study.

No. 1: Page 16 of 49, 2.5. paral : The study will only be initiated after receipt of theapproval from IRIVIECT (add also) and other regulatory agencies as applicable inIndia

No. 2: Baclolen slow release is not included in the title of the document.

Page No. 0 I 0103

CHAIRPERSON:

Dr. R. V. Bhatt D (Obs Gml.)

WM hers of VEC:

. Dr. G.N.Vaishnav M.D (Go) Mcd

Dr. Vipul Desai M.D. (Gcn Mcd)

Dr. V ikas Ponda M D ( Psych.. )

Mr. Atul Mehta BA L L.B

Mrs. Sangita Patel B.SC. (Zoology)

Dr. B.P. Udwadia M D Pligrolgoology

Dr. Darshak Shah Si.s.(Ge„.s.,

Dr. Ashish Sethi (pGi,

Mrs. Snehal Bhatt

No. 3: The proposal for this trial with slow release baclofen would also need references for the availabihty• ZYF c I

this formulation, internationally or nationally. Is this a new formulation altogether? Is due permission fromregulatory authorities available and studies available too?

No. 4: Justification for baclofen slow release for this trial.

No. 5: Considering the results in CLR 09_03 the two important acceptable parameters for equivalence (Cmaxand AUCO-inf) have the average baclofen levels consistently low for 1309 across the dosese of interest, namely10. 20, 30mg in comparison to 13aclolen tables (table 15 page 34 of 49 in Investigator's brochure). Safety wasalso demonstrated for the dose levels studied.

The LSM's in table 16 (page 35 of 49 in Investigator's brochure) indicate a poor bioavailability of baclofenfrom B09. All the dose levels studies in CLR 09 03 have the LSM not within the acceptable level of 80-125% of log transformed data. The present proposed study has the same sex and number of volunteers. Thestudy results of CLR . 09_03 hold true for all the dose levels studied but may need more volunteers for robuststatistical conclusion.As this is not the case in CLR 09 04, is the proposed study CLR 09 04 with a new formulation of 1309?The above mentioned points need to be clarified and accordingly the protocol can he revised and submitted toVadodara Ethics Committee.Approval Status: Deferred- no decision can be made yet, pending evaluation of additional requestedinformation

Date: 28-02-12â VEC reviewed the responses, list of change and updated protocol and approved the study.

Page No. 02 of 03

4. DCG1 Approval Letter and Insurance policy for the trial

Date: 23-

Yours truly,

Dr. R. V. 13hatt

With respect to above referenced study, the Vadodara Ethics Committee certifies that: v E cI. The members of Vadodara Ethics Committee comply with the membership requirement for Independent Ethics Committee

defined in the Ethical Guidelines of Indian Council of Medical Research for Biomedical Research on Human Participants.The committee has reviewed the research proposal with a view to safeguard the dignity, rights, safety and wellbeing of allresearch subjects.Atleast five (5) eligible voting members were present to compose the quorum among which at-least one member was fromscientific area. one from non-scientific area/layperson. one clinician and one from each gender.

This Vadodara Ethics Committee carries out its function in a manner consistent with Good Clinical Practices for clinicalresearch in India.

Out of to members who have attended the meeting ..IQ members have voted in favour of approval, 00 votedagainst and member/s were absent.After consideration Vadodara Ethics Committee has decided to approve this clinical project which is to be conducted atClinical Pharmacology Unit, Sun Pharmaceutical Industries Limited, Tandalja Vadodara with Dr. Aman Khanna as

Principal Investigator and Sun Pharma Advanced Research Company Ltd. as Sponsor.The present approval is valid only for one year: investigator must take the reapproval after one year i f' study isnot initiated.

The following documents were reviewed and discussed on 16-02-2012:

Version/ Date Amendment/ Date

1 Protocol CLR 09 04 02, 28/01/12 00

The following documents were reviewed and discussed on 28-02-2012:

Version/ Date Amendment/ Date

1 Protocol Cl,R 09 04 03, 24/02/12 00

3. Listo f Changes

4 ' Response to the comments raised during EC meeting dated 16-02-2012

The protocol (Version 03),VIS and ICF are approved without any changes.

It is the policy of the Vadodara Ethics Committee to be informed any changes in the approved documents and all seriousadverse events occurring during the course of the study, for the committee to decide further plan of action.

The Vadodara Ethics Committee expects to be informed about any serious adverse event occurring in the course of thestudy, any changes in the protocol and informed consent and asks to provide the progress report after one year to IEC forreview and a copy of the final report after completion of the study.

Investigator should conduct the study as per the recommended GCP guidelines and the approval is given to conduct thestudy in its presented form.

The approval is given to conduct the study in its presented form and approval from the Drugs Controller General (India)should be obtained as per DCGI requirement before initiation of the study.

Page 3 of 3

3ADODARA - .'EERACE COURSE .

VADODA RA - 390007

3.

2 Volunteer Information Sheet &Informed Consent Form (English,Gujarati, Hindi)

Investigator's Brochure for 1309

02, 28/01/12

02, 23/01/12