Group for Research Advancement in Clinical Ethics Regd. Office ti Secretariat: Manobal Klinik, A-2, Rajouri Garden, New Delhi 110027

Telefax: (01 1 ) 25172059 1 25934802 Email: drskdas@gmail.com

President Dr. K. Satyanarayana Dr. Rajesh Nagpal Chief, Division of Publication & Principal Investigator Information Manobal Klinik And Intellectual Property & Rights A-2, Rajouri Garden,

Indian Council of Medical Research New Delhi - 110027

V. Rarnalingaswarni Bhawan, Date: 8th Dec 2010 Ansari Nagar, New-Delhi-110029 (INDIA) Ref: CL3-20098-074: Efficacy and safety of agomelatine with

flexible dose (25 mg/day with blinded potential adjustment Secretary General: at 50 mg) given orally for 8 weeks in Indian outpatients

Dr. S.K. Das with Major Depressive Disorder. A randomised double-blind national multicentric study with

Manobal Klinik parallel groups, versus sertraline (50 mg/day with blinded A-2, Rajouri Garden potential adjustment at 100 mg). New Delhi-110027 Tel: 0981 0537325 Subject: Study Conduct as per Ethics Committee Approval

E-rnail:drsrikrishnnadas@gmail.com Dear Dr. Rajesh Nagpal,

Yice - President: The independent ethics committee (GROUP RESEARCH Dr. Smita N. Deshpande ADVANCEMENT I N CLINICAL ETHICS) has reviewed and discussed Head, Dept. of Psychiatry, your application on 06.12.2010, to conduct the clinical trial entitled or. flarn ~~~~h~~ Lohia Hospital, "CL3-20098-074: Efficacy and safety of agomelatine with flexible

Park Street, New Delhi - 110001 dose (25 mg/day with blinded potential adjustment at 50 mg) given

Tel: 23404269,23442122 orally for 8 weeks in Indian outpatients with Major Depressive Disorder.

E-mail:smitadeshp@~mail.cOm A randomised double-blind national multicentric study with parallel groups, versus sertraline (50 mg/day with blinded potential adjustment at 100 mg)."

Dr. R.K. Bhatia D-11131, Janak Puri,

New Delhi - 1 10058

You submitted the required documents to the Ethics Committee on 04.11.2010 that were reviewed and approved during this meeting.

Tel: 28520968 The Independent Ethics Committee GRACE will supervise the study Email: rkbhatia57Qrediffrnai1.com conduct at the site and review and provide opinions as necessary to

ensure safety of the patients and ethical conduct of the trial.

Final report of the study shall be submitted to the Ethics Committee in all cases, even when the study is abandoned for any reason(s).

Yours sincerely,

Dr. S.K. Das Secretary General, Ethics Committee, (GRACE)

Group for Research Advancement in Clinical Ethics Regd. Office & Secretariat: Manobal Klinik, A-2, Rajouri Garden, New Delhi 110027

Telefax: (01 1) 25172059 / 25934802 Email: drskdas@gmail.com

President: Dr. K. Satyanarayana

Date: 08.12.2010

Chief, Division of Publication & Information

Dr. Rajesh Nagpal

And Intellectual Property & Rights Principal Investigator

lndian Council of Medical Research Manobal klinik

V. Ramalingaswami Bhawan, A-2, Rajouri Garden,

Ansari Nagar, New-Delhi-110029 New Delhi - 110027

(INDIA)

Secretary Generat Ref: CL3-20098-074: Efficacy and safety of agomelatine with flexible

Dr. S.K. Das dose (25 mg/day with blinded potential adjustment a t 50 mg) given Nlanobal Klinik orally for 8 weeks in Indian outpatients with Major Depressive Disorder. A-2, Rajouri Garden A randomised double-blind national multicentric study with parallel New Delhi-110027 groups, versus sertraline (50 mg/day with blinded potential adjustment Tel: 0981 0537325 a t loo mg). E-mail:drsrikrishnnadas@gmail.com

Vice - President: Dr. Smita N . Deshpande Head, Dept. of Psychiatry, Dr. Ram Manohar Lohia Hospital, Park Street, New Delhi - 110001 Tel: 23404269,23442122 E-mail: smitadeshp@gmail.com

Treasurer: Dr. R.K. Bhatia 0.11131, Janak Puri,

Subj: Ethics Committee Approval for the Protocol No. CL3-20098-074

Dear Dr. Rajesh Nagpal,

The independent ethics committee (Croup Research Advancement in Clinical Ethics) has reviewed and discussed your application on <06.12.2010 >, to conduct the clinical trial entitled "CL3-20098-074: Efficacy and safety of agomelatine with flexible dose (25 mglday with blinded potential adjustment at 50 mg) given orally for 8 weeks in lndian outpatients with Major Depressive Disorder. A randomised double-blind national multicentric study with parallel

New Delhi - 110058 groups, versus sertraline (50 mg/day with blinded potential adjustment at Tel: 28520968 100 mg)."

\ E-mail: rkbhatia57@rediffmail.com

You submitted to the Ethics Committee on < 04.11.2010 > following documents that were reviewed and approved during this meeting:

I. Clinical Trial Protocol - CL3-20098-074 (Final version dated 2gth June

2010 )

2. CL3-20098-074 - Investigator Brochure (Version 15 dated 29" June

2009)

3. CL3-20098-074 - Case Report Form Final Version (1.0) dated 3oth

June 2010

4. CL3-20098-074 - Patient Questionnaire Final Version (1.0) dated 3oth

June 2010 - English Page 1 of 2

Group for Research Advancement in Clinical Ethics Regd. Office & Secretariat: Manobal Klinik, A-2, Rajouri Garden, New Delhi 110027

Telefax: (01 1 ) 251 72059 I 25934802 Email: drskdasQgmail.com

President: Dr. K. Satyanarayana Chief, Division of Publication & lnformation And Intellectual Property & Rights Indian Council of Medical Research V. Ramalingaswami Bhawan, Ansari Nagar, New-Delhi-110029 (INDIA)

Secretary Generak Dr. S.K. Das Manobal Klinik A-2, Rajouri Garden New Delhi.110027 Tel: 0981 0537325 E-mail:drsrikrishnnadas@gmail.com

Vice - President Dr. Smita N . Deshpande Head, Dept. of Psychiatry, Dr. Ram Manohar Lohia Hospital, Park Street, New Delhi - 110001 Tel: 23404269,234421 2 2 E-mail: smitadeshp@gmail.com

Treasurer: Dr. R.K. Bhatia D-11131, Janak Puri,

New Delhi - 110058 Tel: 28520968 E-mail: rkbhatia57@rediffmaiI.com

5. CL3-20098-074 - Patient Questionnaires Final Version (1.0) dated

30th June 2010 - Hindi

6. Translation Certificate: Sheehan Disability Scale dated 0 6 ' ~

September 2010

7. Translation Certificate: LEEDS Sleep Evaluation Certificate dated

0 6 ~ ~ September 2010

8. Translation Certificate: Hospital Anxiety Depression dated 22nd June

2010

g. CL3-20098-074 - Participant lnformation and Consent Form Final

Version dated 25th June 2010 - English

10. CL3-20098-074 - Participant lnformation and Consent Form Final

Version dated 25th June 2010 - Hindi

11. Translation Certificate: Participant lnformation and Consent Form

dated 7th September 2010

12. CL3-20098-074 - Patient Card Version dated 22"d July 2010 - English

13. CL3-20098-074 - Patient Card Version -Hindi

14. Translation Certificate: Patient Card dated 17 September 2010

15. Confidentiality Agreement - CL3-20098-074 - signed igth ~ u g u s t

2010

16. Certificate o f Insurance - Policy Number LPoooo12~80001oo dated

0 8 ~ ~ July 2010

17. Submission Letter, DCGl - CL3-20098-074 dated 3oth July 2010 -

acknowledgement dated 06" August 2010.

18. Curriculum Vitae - Dr. Nagpal dated 2gth April 2010

19. Medical Registration Certificate - Dr. Nagpal

20. Investigator Undertaking signed on oiSt July 2010

21. CL3-020098-074 - Investigators list - 25" June 2010

22. Clinical Trial Agreement

Page 2 of 4

Group for Research Advancement in Clinical Ethics Regd. Office 6: Secretariat: Manobal Klinik, A-2, Rajouri Garden, New Delhi 110027

Telefax: (01 1) 25172059 1 25934802 Email: drskdasQgmail.com

President: Dr. K. Satyanarayana The following members of the Ethics Committee were present in the

Publication meeting held on 6th Dec 2010, 3.00 pm at Dr. Satyanarayana's office ICMR lnforrnation and were involved in the approval process: And Intellectual Property & Rights Indian Council of Medical Research V. Ramalingaswami Bhawan, Ansari Nagar, New-Delhi-110029 (INDIA)

Secretary Generak Dr. S.K. Das Manobal Klinik A.2, Rajouri Garden New Delhi-110027 Tel: 09810537325 E-mail:drsrikrishnnadas@gmail.com

Vice - President: Dr. Smita N . Deshpande Head, Dept. of Psychiatry, Dr. Ram Manohar Lohia Hospital, Park Street, New Delhi - 110001 Tel: 23404269,23442122 E-mail: smitadeshp@gmail.com

Treasurer: Dr. R.K. Bhatia D-11131, Janak Puri,

New Delhi - 110058 Tel: 28520968 E-mail: rkbhatia57@rediffrnaiI.com

The EC during its meeting decided to approve the conduct of the above study in i ts present form.

It is also confirmed that neither you nor any of the study team members participated in the voting procedure.

Further to the above we would like to confirm the following:

This Ethics Committee functions in accordance with ICH-GCP & Schedule Y. The documents listed above constitute the complete set of documents to be subjected to EC review a t this institute. We shall retain the above documents for 15 years.

You are expected to report to the Ethics committee the following:

All deviations from, or changes to, the protocol to eliminate immediate hazards to the study subjects Changes that increase the risk to participating subjects and/or those that significantly affect the conduct of the study Any serious adverse events occurring in the course of the study within 14 calendar days of their occurrence. New information that may affect adversely the safety of the subjects or the conduct of the study Any changes in the protocol and patient information / informed consent documents, prior to their implementation.

Page 3 of 4

Dr. S.K. Das Member Secretary Ethics Committee

Group for Research Advancement in Clinical Ethics Regd. Office ti: Secretariat: Manobal Klinik, A-2, Rajouri Garden, New Delhi 110027

Telefax: (01 1) 25172059 1 25934802 Email: drskdas8gmail.com

President: Dr. K. Satyanarayana Progress of t he study a t 6 months. Chief, Division of Publication & Information Final report of t h e study shall be submitted t o t he Ethics Committee in all And Intellectual Property & Rights Indian Council of Medical Research

cases, even when the study is abandoned for any reason(s).

V. Ramalingaswami Bhawan. Ansari Nagar, New-Delhi-110029 (INDIA)

Secretarv Generak Dr. S.K. Das Manobal Klinik A-2, Rajouri Garden Aew Delhi-110027 Tel: 09810537325 E-rnail:drsrikrishnnadas@gmail.com

Vice - President: Dr. Smita N. Deshpande Head, Dept. of Psychiatry, Dr. Ram Manohar Lohia Hospital, Park Street, New Delhi - 110001 Tel: 23404269,234421 22 E-mail: smitadeshp@gmail.com

Treasurer: Dr. R.K. Bhatia

0-11131, Janak Puri, New Delhi - 110058 Tel: 28520968 E-mail: rkbhatia57@rediffmaiI.com

Page 4 of 4

Consultant Neuro Psychiatrist

Member Secretary (GRACE) A-2, Rajouri Graden, New Delhi - 110027

A-2, Rajouri Garden, New Delhi-110027

Telefax: 01 1 -251 72059125934802 9810037469,9312273149 drrajeshnagpal'@ sify.com

drrajeshnagpal23 @ gmail.com

Date: 08.12.2010

Ref: CL3-20098-074: Efficacy and safety of agomelatine with flexible dose (25 mg/day with blinded potential adjustment a t 50 mg) given orally for 8 weeks in Indian outpatients with Major Depressive Disorder. A randomised double-blind national multicentric study with parallel groups, versus sertraline (50 mglday with blinded potential adjustment a t loo mg).

Subject: Study Conduct as per Ethics Committee Approval

Dear Sir,

This is regarding the Ethics Committee (EC) submission for the above mentioned study on 04.11.2010 and subsequent approval on 8th Dec 2010.

Please note that the study will be conducted in accordance with the approval statement granted by GROUP RESEARCH ADVANCEMENT IN CLl NlCAL ETHICS.

Kindly let me know if you need any additional information/clarifications.

Thanking You

Yours Sincerely

Dr. Rajesh Nagpal (Principal Investigator) Manobal Klinik A-2, Rajouri Graden, New delhi - 110027