.. * " ,.

KLE UNIVERSITY t"O~n'I.G~"f: t>Ji5

KLE UNIVERSITY [Established under Section 3of the UGCAct. 1956 vide MHRO, G.O.I Notification No.F.9-19/2000-UJ (A) dt. 131h April 2006j

Off ice of the Registrar, KLE University, JNM C Campus, Nehru Nagar, Belgaum-590 010, Karnataka State, India

: 0831-2472777 FAX: 0831-2493777 Web : http ://www.kleuniversity.edu .in E-mail: regist rar@kahe .edu .in

Ref: KLEU/EC/201 0-11/ I 6 t> 0 9 . Dated: 10/12/2010

To,

Dr.Rekha Patil. Principal Investigator & Professo r of Medicine, Site Management Office, KLES Dr Prabhakar Kore Hospital & Medical Research Center, Nehru Nagar, Belgaum .

Ref: A Multicenter, Random ized, Doubl e-Blind, Placebo -Controlled, Parallel group, Phase III Trial to

evaluate the Safety and Efficacy of Dapagliflozin in subjects with Type 2 Diabetes with

inadequately controlled Hypertension on an Angiotensin-Converting Enzyme Inhibitor (ACEI) or

Angiotens in Receptor Blocker (ARB).

Dear Dr. Rekha Patil,

The Ethics Committee meeting of KLf: l Iniversity was held T hursday, 09111 December, 2010 at 3 :30

pm At Site Management Office, KLES Dr Prabhakar Kore Hospital & MRC, Belgaum

We have received fr om you 12 Copies of the following

1. Protocol MB I02 073 date d 18-Au g-2010 (Revised Protocol Number: 01, Incorporates ame ndment(s) 02)

2. Protocol amendment 02 dated 18-Aug-20 10 (Summary of changes)

3. Pharmacogenetics Blood Sample Amendment umber 01 dated 06-May- 20 10

4. Investigator's Brochure Version 06 dated 04-N ov-2009

5. Expedited Safety Reports

Date of Report Report Identifier Event 04-Jan-10 ESR #1 Ureteric calculus 09-Feb-10 ESR #2 Bladder Transitional Ce ll

KLE UNIVERSITY [Established under Section 3 of the UGC Act, 1956videMHRD, G.O.I NotificationNoF.9-19/2000-U.3(A) dt 13'"April 2006j

Office of the Registrar , KLE University , JNMC Campus . Nehru Nagar , Belgaum-590 010. Karnataka State , India

fiI' : 0831-2472777 FAX: 0831-2493777 Web: http://www.kleuniversity.edu.in E-mail: registrar@kahe.edu .in

Carcinoma 12-Feb-lO ESR #3 Cardiac Failure Congestive 22-Mar- l 0 ESR #04 Renal Cancer 25-Mar-l0 ESR #05 Bacterem ia 31-Mar- l 0 ESR #06 Renal Failure 06-Apr-l0 FU # 1 to ESR #05 Bacteremia (removed) 12-Apr-l 0 ESR #07 Cerebrovascular Accident II-Jun-l0 ESR #08 NephroIithiasis 29-Jul- l0 ES R #09 Calculus Bladder 14-Sep-l0 ESR # 10 Aortic Aneurysm 16-Sep-l0 ESR # 11 Urinary Tract Infection 12-0ct-l0 FU # 1 to ESR # 11 Sepsi s & Urinary Tract Infection 25-Sep-l0 ESR# 12 Anemia 08-0 ct-l0 ESR # 13 Renal Failure Acute

6. Site Specific Main Subject Information Sheet and Inform ed Consent Form - Tran slations and Back­translations (12 copi es)

a) MBI 02073 GLOBAL MASTER MAIN ICF V2 , INDIA VI , SITE 165 V I , 11 NOV 2010 (ENGLI SH)

b) MB I02073 GLO BAL MASTER MAIN ICF V2, INDIA VI , SITE 165 V I , 11 NOV 2010 (HIN DI)

c) MB I02073 GLOBA L MASTER MAIN ICF V2, IND IA VI , SITE 165 VI , 11 NOV 2010 (HINDI) BT

d) MB I02073 GLOBAL MASTER MAIN lCF V2, I TDIA VI , SIT E 165 V I , 11 NOV 2010 (KANN ADA)

e) MBI0207 3 GLOB AL MASTER MA IN ICF V2 , IN DIA VI , SITE 165 V I , 11 NO V 2010 (KANNADA) BT

1) MB I02073 GLOBAL MASTER MAIN ICF V2, INDIA VI , SITE 165 V I, 11 NOV 2010 (MARAn -II)

g) MBI02073 GLOBAL MASTER MAIN ICF V2 , INDIA VI , SITE 165 VI , 11 NOV 2010 (MA RATHI) BT

7. India Main Subj ect Info rmation Sheet and Informed Consent Form

MB 102073 GLOBAL MASTER MAIN ICF V2, INDIA VI , 15 SEP 20 10

· . ~ >i."

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KLE UNIVERSITY [Established underSection 3 of the UGCAct, 1956 videMHRD, Gm Notification NoF 9-19/2000-UJ (A)dt 13th April 2006]

Office of the Registrar, KLE University, JNM C Campus, Nehru Nagar, Belgaum-590 010, Karnataka State , India

2 : 0831-2472777 FAX: 0831-2493777 Web: http://www.kleuniversity.edu.in E-mail: registrar@kahe.edu.in

a. Hindi

b. Hindi Back-translation

c. Kannada

d. Kannada Back-translation

e. Marath i

f. Marathi Back-trans lation

8. Site Specific Pharmacogenet ic Addendum Subject Info rmation Shee t and Informed Consent Form ­Eng lish - MBI 02073 GLOBAL MASTER PGx ICF V I , IN DIA V I , SITE 165 V I, 11 NO V 20 10 (ENGLISH)

9. Ind ia Phar macogenetic Addendum Su bject Information Sheet and Informed Consent Form

MBI 02073 GLOBAL MASTER PGX ICF,V l , INDIA V I , 29 JUL 2010

a. Hindi

b. Hindi Back-translation

c. Kannada

d. Kannada Back-trans lation

e. Marathi

f. Marath i Back-translation

10. Site Specific Pre-screening Subject Information Sheet and Informed Consent Form - Translations and Back-translations (12 copies)

a) MBI02073 GLOBAL MASTER PRE-S CR EENING ICF V2, INDIA V I, SITE 165 V I, 11 NOV 20 10 (ENGLI SH)

b) MB I02073 GLOBAL M ASTER PRE-SCRE ENING ICF V2, INDIA V I, SITE 165 V I , 11 NOV 20 10 (HINDI)

c) MB I02073 GLOBAL MASTER PRE-S CREENING ICF V2 , INDIA V I , SITE 165 VI, 11 NOV 2010 (HIN DI) BT

d) MBI 02073 GLOBAL MASTER PRE-SCREE ING ICF V2, INDIA V I, SITE 165 V I , 11 NOV 20 10 (KA NNADA)

e) MB I 02073 GLOBAL MASTER PRE-SCREENI NG ICF V2, INDIA VI , SITE 165 V I, 11 NOV 2010 (KA NNADA) BT

KLE UNIVERSITY [Established underSection 3 of the UGC Act, 1956 vide MHRD, G.O.I Notification No.F9-19/2000-U.3(A) dt, 13'"April 2006J

Office of the Registrar, KLE University, JNM C Campus, Nehru Nagar, Belgaum-590 010, Karnataka State, India

'Iif: 0831-2472777 FAX : 0831-2493777 Web: http://www.kleunivers ity .edu. in E-mail: re gistrar@kahe.edu.in

f) MB I02073 GLOBAL MASTER PRE-S CREENING ICF V2, INDIA V I, SITE 165 V I , 11 NOV 2010 (MARATH I)

g) MB102073 GLOBAL MASTER PRE-SCREEN ING ICF V2, INDIA V I , SITE 165 VI, 11 NOV 2010 (MARATHI) BT

11. India Pre-screening Subject Inform ation Sheet and Inform ed Consent Form MBI02073 GLOBAL MASTER PRE-S CREENING ICF , V2 INDIA VI, 29 JUL 20 10

a. Hindi

b. Hindi Back-trans lation

c. Kannada

d. Kannada Back-translation

e. Marathi

f. Marathi Back-trans lation

12. Patient Card India Version 1, 21 Oct 20 10

a. Hindi

b. Kannada

c. Marathi

d. Engli sh

13. Patient log book Version dated 11 Jun 20 10

a. Hindi

b. Kannada

c. Marathi

d. English

14. eCRF pri nt dated 07 Sep 20 10 (l Copy)

15. BMS letter dated 03 Nov 2010 regarding Insurance (1 Copy)

16. Clinical Trial Agreement (1 copy)

RO W Tripart ite Master CTA 21 June 20101 India Vl _18 Aug 20101Dr. Rekha PatilV I_06-0ct-2010

17. Copy of application letter to DCGI dated 20 Sep 20 10 for the con duct of the study (1 copy)

18. Copy of CV and MRC.

KLE UNIVERSITY [Established under Section 3 of the UGCAct, 1956 vide MHRD, G.O.I Notification No.F.9-19/2000-U.3(A) ot. 13'hApril 2006]

Office of the Registrar , KLE University , JNM C Campus, Nehru Nagar , Belgaum- 590 010, Karnataka State, India

if : 0831-2472777 FAX: 0831-2493777 Web : http ://www.kleunivers ity.edu.in E-mail : registrar@kah e.edu.in

19. Undertaking of Principal Investigator.

At the Ethics Committee meeting held on Thursday 09 1h December, 2010 at 3:30 pm your

referenced letter and the above submitte d documents were examined and discussed .

Discussion P oin ts ­

Clarification requested ­

The Ethics Committee had some concern about the safety of study participants, Fasting blood

glucose less than 270 mg/d l no rescue tre atm ent is adv ised, rescue treatment is adv ised only when level

crosses 270mg/d l for 3 months, Investigator is requested to clarify thi s point.

The Committee has also reques ted the investigator to Comply with the following ­

• The DCGI approva l letter.

• Insurance Certificate for the study part icipants.

• Site specific Informed Consent Fo rms.

The members who attended the meetin g held on T hu r sd ay 09 th December, 2010 at 03:30 pm At Site

M a nagem en t O ffic e, KLES Dr Pra bhaka r Kore Hospita l & MRC, Belgaum.

Following M em bers of th e Committee were present:

1. Dr. Sanj iva Kholkute, Officer-in-Charge, RMRC, Belgaum Chairman

2. Dr. P. A. Pati l, Jo int Director, KLE University Research Foundation Member

3. Dr. Ashok C. Pangi , Prof of Sur gery, JNMC, Belgaum Member

4. Dr. S.M.Dhaded, Professor & HOD Dept of Pedi atri c, J.N .M .C, Bgm Member

5. Dr. Sunita. Y. Patil , Ass ist Professor, De pt of Path ology, J.N .M .C, Bgm Member

6. Dr. Subama.Roy, Scientist ' D' Officer-in-cha rge, RMRC (lCMR), Belgaum Member

7. Mr. B.N.Metagudmath, Re td . Dy.SPs, Vi gilance Officer, KL ESH, Be lgaum Member

8. Mrs . Maki N. Kapadi a, Socia l Worker, Havel ock Road , Camp, Belgaum Member

9. Mr. N .D.Kunne, Ad voc ate & Receiver Bgm Dist.Co urt, Belgaum Member

10. Dr. S.S.G oudar, Prof of Physiology, JNMC, Belgaum Member - Secretary

KLE UNIVERSITY� [Established under Section 3 of the UGC Act, 1956 vide MHRD, G.O.I NotificationNo.F.9-19/2000-U.3(A) dt. 13'hApril 2006]

Office of the Registrar, KLE University,� JNM C Campus , Nehru Nagar, Belgaum-590 010 , Karnat aka State, India�

if:0831-2472777 FAX: 0831-2493777 Web : http://www.kleun ivers ity.edu.in E-mail: registrar@kahe.edu.in

Following Members of the committee were unable to atta in the meeting as they were on duty leave:­

1.� Dr. M. B. Bellad, Prof OBGYN, JNMC, Bel gaum Member

You are requested 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 subj ects and /or those that significantly affect the

conduct of the study

•� All serious adverse events�

•� New information that may affect adversely the safety of the subj ects or the conduct of the study�

•� Any changes in the study document�

• Pro gress of the study.�

A lso please provide a report to the Ethics Committee on the completion of the study. If you have any�

que stions concerning the above, please feel free to contact the committee office.�

Ne ither the PI nor any of the proposed study team members were pre sent during the dec ision-making procedures of the Ethics Committee.

Note: Pharmacogenomic study in any form is not approved by the Ethics Committee

Yours truly ,

(Nam ,- a ture oCE~~ic s Comm ittee UJiJHIIO~lMem b e I: SeC!"'fUry)

,. -~ , ' ... ~ ~\

I I 'J ~

KLE UNIVERSITY [Es tablished under Section3of the UGC Act, 1956 videMHRD,.G,O,I Notification No,F,9-1 9/2000-U.3(A) dt. 13'" April 2006]

OHRP: IRB00008025 KLE University IRB #1

Office of the Registrar , KLE University , JNMC Campus , Nehru Nagar, Belgaum-590 010, Karnataka State , India

tit : 0831-2472777 FAX: 0831-2493777 Web: http://www.kleuniversity.edu.in E-mail: registrar@kahe.edu.in

Ref: KLEU/EC/2010-11 !J:J - :2-/7 {,b Dated: 16/03/2011

To, Dr.Rekha Patil. Principal Investigator & Professor of Medicine, Site Management Office, KLES Dr Prabhakar Kore Hospital & MRC, Nehru Nagar, Belgaum.

Ref: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel group, Phase III Trial to

evaluate the Safet y and Efficacy of Dapagliflozin in subjects with Type 2 Diabetes with

inadequately controlled Hypertension on an Angiotensin-Converting Enzy me Inhibitor (ACEI) or

Angiotensin Receptor Blocker (ARB).

Sub: Approval for the conduct of the above referenced study.

Dear Dr. Rekha PatH, The Ethics Committee meeting ofKLE University was held Tuesday is'" Ma rch, 2011 at 11:30am

in Site Management Office, KLES Dr Prabhakar Kore Hospital & MRC , Belgaum.

Discussion Points ­

During its meeting, Ethics Committee reviewed & discussed the clarifi cation submitted by the

investigator. The members were convinced by the clarification and decided to grant the approval for the

conduct of the above referenced study.

The members who attended the meeting held on Tuesday 151h March, 2011 at 11:30am in Site

Management Office, KLES Dr Prabhakar Kore Hospital & MRC, Belgaum.

Following Members of the Committee were present:

1. Dr. Sanjiva Kholkute, Officer-in-Charge, RMRC, Belgaum Chairman

2. Dr. P. A. Patil, Joint Director, KLE University Research Foundation Member

3. Dr. S.M.Dhaded, Professor & HOD Dept of Pediatric, J.N.M.C, Bgm Member

4. Dr. Ashok C. Pangi. Prof of Surgery, JNMC, Belgaum Member

5. Dr. M. B. Bellad, ProfOBGYN, JNMC, Belgaum Member

0.�

KLE� U N IVERSITY ~1llCf3IIOolU

KLE UNIVERSITY� [Established under Section 3 of theUGCAct, 1956 vide MHRD, G,O, I Notification No.F,9-19/2000-U.3(A) ct 13'" April 2006J�

OHRP : IRB00008025 KLE University IRB #1�

Office of the Registrar, KLE University,� JNMC Campus, Nehru Nagar, Belgaum-590 010, Karnataka State , India�

V : 0831-2472777 FAX: 0831-2493777 Web: http://www.kleuniversity.edu.in E-mail : registrar@kahe.edu.in

6.� Dr. Subarna. Roy, Scientist '0 ' Officer-in-charge, RMRC (ICMR), Belgaum Member

7.� Mrs. Maki N. Kapadia, Social Worker, Havelock Road, Camp, Belgaum Member

8.� Mr. N.D.Kunne, Advocate & Recei ver Bgm Dist.Court, Belgaum Member

9.� Dr. S.S.Goudar, Prof of Physiology, JNMC , Belgaum Member - Secretary

Following Members of the committee were unable to attain the meeting as they were on duty leave:­

1.� Dr. Sunita. Y. Patil. Assist Professor, Dept of Pathology, IN.M.C, Bgm Member

2.� Mr. B.N.Metagudmath, Retd. Dy.SPs, Vigilance Officer, KLESH, Belgaum Member

You are requested 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

•� All serious adverse events�

•� New information that may affect adversely the safety of the subjects or the conduct of the study�

•� Any changes in the study document�

• Progress of the study.� Also please provide a report to the Ethic s Committee on the completion of the study. If you have any�

questions concerning the above, please feel free to contact the committee offi ce,�

Neither the PI nor any of the proposed study team members were present dur ing the decision-making procedures of the Ethics Committee.

Note: Pharrnacogenornic study in any form is not approved by the Ethics Com mittee

Yours truly,

(Name & Signature of Ethics Committee Chairman/Member Secretary)

I� • I •