Recommendations of the SEC (Endocrinology & Metabolism) made in its 63rd meeting held on 23.01.2020 at CDSCO HQ New Delhi:

File Name & Drug Name, S.No Firm Name Recommendations Strength New Drugs Division The committee deliberated the safety issue of increased risk of leg and foot amputations with . After detailed deliberation the committee recommended that 12-74/13-DC 1 Internal Discussion CDSCO should request the State Canagliflozin Tablet Drugs Controllers to direct the manufacturers of the drug to include following warning: “Canagliflozin causes an increased risk of leg and foot amputations”. Biologicals Division Firm presented their proposal for additional indication for aspart (Fiasp) in peaderitic and adolescent population. The firm presented Phase III clinical trial data in which 59 Indian patients were part 04-62/Novo Nordisk/PAC- of the study. 2 R-/19-BD M/s Novo Nordisk The committee noted that the safety Fiasp (Insulin Aspart) and efficacy data of the Indian subset is in-line with the global data. Further, the indication is approved in US, EU, etc. After detailed deliberation, the committee recommended for approval of additional indication. In light of the recommendations by the SEC in its meeting dated 21.05.2019, the firm presented the justification for conduct of PMS study in place of Phase IV study. The committee noted that the firm has conducted four Phase III global clinical trials in which 172 Indian 2/Phase IV/Novo patients were enrolled. Further, the 3 Nordisk/19-BD M/s Novo Nordisk firm presented that the data Fiasp (Insulin Aspart) generated from the Indian subset is in-line with the global clinical data. After detailed deliberation, the committee recommended that the request of the firm to conduct PMS study may be accepted. Accordingly, the firm should present the protocol for approval.

63rd SEC (Endocrinology & Metabolism) 23.01.2020 File Name & Drug Name, S.No Firm Name Recommendations Strength Firm presented their Phase IV clinical trial protocol. 4 BIO/Form M/s M. J. Biopharm After detailed deliberation, the 44/FF/2019/15526 Pvt.Ltd committee recommended for grant of Biphasic Isophane Insulin permission to conduct the study as per the presented protocol. Subsequent New Drugs Division The firm presented BE study protocols for single dose and multiple doses before the committee. After detailed deliberation, the committee recommended for grant of permission to conduct the BE studies SND/MA/19/000099 subject to conditions that limits of Sustain M/s Exemed the laboratory values shall be clearly 5 Release Tablet 100 mg Pharmaceuticals specified in the inclusion and (add. Strength) exclusion criteria of the study protocols. Revised protocols should be submitted to CDSCO for approval. However, the committee recommended that phase III clinical trial should also be conducted. FDC Division The firm presented their protocols for BA study and phase-III clinical trial. After detailed deliberation, the committee recommended for grant of permission to conduct the proposed BA study with the condition that one Physician with postgraduate qualification shall be included in the study. FDC/MA/19/0000151 As regard to phase-III clinical trial protocol the committee + Hydromide M/s. Glenmark recommended for grant of 6 Hydrate IP Eq. to Pharmaceuticals Ltd. permission to conduct the proposed Teneligliptin (100mg clinical trial study with following +10mg) Film coated tablets condition:

1) The rescue criteria should be revised to include FBG at 6 weeks should be 240 instead of 270. 2) There should be appropriate withdrawal criteria. The trial should be initiated only after completion of BA study and result should be presented before the committee.

63rd SEC (Endocrinology & Metabolism) 23.01.2020 File Name & Drug Name, S.No Firm Name Recommendations Strength The firm presented BE study protocol before the committee. After detailed deliberation the committee recommended for grant of permission subject to the following conditions:- 1. The firm should revise the inclusion and exclusion criteria specific to the proposed study. FDC/MA/19/000134 2. Limits of the laboratory HCl IP values shall be clearly 7 500mg/1000mg (sustained M/s. Mascot specified in the protocol. release) + Vildagliptin 3. A Physician with post 50mg/50mg graduate qualification in Medicine should be part of the study team. Accordingly, firm should revise the BE study protocol and submit to CDSCO for further consideration. The firm should present BE study data before the committee for further consideration of conduct of Phase III Clinical trial.

The firm presented their proposal along with phase-III clinical trial and BE Protocol before the committee. After detailed deliberation, the committee noted that:- 1. There is potential high risk of Hypoglycemia with the FDC/MA/19/000161 proposed FDC compared to Phosphate two drug approved FDCs as Monohydrate IP Eq. to well as individual Sitagliptin 50mg/50mg + ingredients. 8 M/s. Sun Pharma Metformin Hydrochloride 2. There is only advantage in IP 1000mg/1000mg + respect of pill burden with the IP 1mg/2mg proposed FDC as compared Film Coated Tablet to two drug FDCs as well as individual drugs approved. 3. The proposed FDC is not approved anywhere in the world. In view of the unfavorable benefit risk ratio, the committee did not recommend for approval.

FDC/MA/19/000041 Firm presented the BE study report Vildagliptin 50 mg/50mg + M/s. Dr. Reddys along with justification for phase III 9 Metformin Hydrochloride Laboratories CT waiver before the committee. IP 500/1000mg (Sustain After detailed deliberation, the

63rd SEC (Endocrinology & Metabolism) 23.01.2020 File Name & Drug Name, S.No Firm Name Recommendations Strength release tablet) committee did not recommend for waiver of the Phase III trial with respect to the proposed indication. Firm presented their Active PMS protocol for proposed FDC before the committee. After detailed FDC/MA/18/000070 deliberation, the committee Evogliptin + Metformin M/s. Alkem Laboratories recommended for conducting 10 Hydrochloride SR (5mg + Ltd proposed study and study sites 1000mg) Tablet should be geographically distributed. The study should be completed and results shall be presented before the committee within 15 months. GCT Division Applicant presented their proposal along with study protocol before the committee. Assessment of risk versus benefit to the patients- The safety profile of the study drug from various preclinical toxicology studies and clinical studies justify the conduct of the trial. Innovation vis-a-vis existing therapeutic- To evaluating the efficacy and safety of tirzepatide CT/92/19 once weekly in participants without 11 M/s. Eli Lilly Tirzepatide Type 2 Diabetes who have obesity or are overweight with weight-related comorbidities. Unmet medical need in the country- To develop safe and efficacious treatment for subjects without Type 2 Diabetes who have obesity or are overweight with weight-related comorbidities. After detailed deliberation the committee recommended for grant of permission to conduct the study.

The applicant presented their study protocol amendment 4(#6 for India) CT/58/17 before the committee. 12 M/s. PRA / After detailed deliberation the committee recommended for approval for the said amendment.

63rd SEC (Endocrinology & Metabolism) 23.01.2020