Name of firm/applicant. Torrent Pharmaceuticals. Glenmark Pharmaceuticals. M/s. Torrent Pharmaceutical. Torrent Pharmaceuticals

Transcription

1 Recommendation:- The 14 Th SEC (Cardiovascular & Renal) deliberated the proposals on and recommended the following:- Agenda no. File no Name of firm/applicant Recommendations /06-D(pt torrent) Amlodipine+Valsartan /14-DC Azelnidipine IP (As Immediate Release Tablet)+Metoprolol Succinate USP eq. to Metoprolol Tartrate (As extended Release Tablet) /07-DC(pt torrent) Amlodipine Besylate eq. to Amlodipine+Olmesartan Medoxomil /2004-DC(pt TPL) Ezetimibe+Simvastatin /14-Dc Perindopril ErbumineBP+Indapamid eip +Amlodipine Besilate IP Torrent Glenmark M/s. Torrent Pharmaceutical Torrent Sardia Firm did not make presentation. Firm did not turn up for presentation. Committee opined that there is no advantage of patient compliance as two tablet of Amlopdipine 5 mg+ Olmesartan 20 mg can be given if required in certain population. Further titration of dose will be difficult with the proposed strength. Therefore committee recommended that the proposed strength Amlopdipine 10mg+ Olmesartan 40 mg is not justified and hence not recommended. Committee noted that the proposed FDC is available in US.Committee recommended for approving Ezetimibe 10 mg+simvastatin 40 mg tablets. However, FDC of Ezetimibe 10 mg+simvastatin 80 mg is likely to be misused in view of potential risk associated and therefore the safety is required to be established in Indian patients before consideration. Hence the committee did not recommendfor Ezetimibe 10mg+Simvastatin 80 mg tablets. In the absence of clinical trial data in Indian patients, permission to manufacture and market the proposed FDC cannot be considered. However, the committee noted that the proposed FDC is already approved in EU as well as Australia. The committee recommended for the proposed Bioequivalence study as per the request of the firm at this stage.

2 6. CT/62/13 Methyprednisolone George Clinical In light of the fact that the test drug is already approved and marketed in India, the safety profile of the test drug justify the conduct of the study. Further, in response to previous query, the investigator has changed the inclusion criteria from 20 ml egr to 30 ml egfr. The purpose of the study is to evaluate the long term efficacy and safety of the drug on a background of routine RAS inhibitor therapy, in preventing kidney events in patients with IgA nephropathy. The data of this study may potentially provide an evidence for preventing kidney events in patients with IgA nephropathy. The applicant has deleted the exclusion criteria of Minimal Change Disease. However, just by exclusion, false inclusion of the minimal change disease will mislead the data conclusion. Thus committees recommend exclusion of those cases where electron microscopy is not available. Investigator has included Mountex Test as criteria for diagnosis of latent TB. However, in Indian context where BCG is universally given, Mountex test will give false positive results. Further, in CKD patients, Mountex test will give false negative tests also. For both the issues, Mountex test will not be appropriate in this clinical setting. Committee recommend including of Quanteferon Gold test for diagnosis of latent tuberculosis. Committee also wishes to see the change of egfr criteria to be applicable in global protocol. Investigator has agreed to give documentary evidence for such change globally. Committees wish to get such evidence as hard copy signed by appropriate global body/person. Accordingly the committee recommended the conduct of the trial subject to the above condition.

3 7. CT/86/13 Telmisartan + amlodipine + hydrochlorthiazide 8. CT/17/14 Nifedipine, labetalol and methyldopa 9. CT/118/12 AMG 145 George Clinical Govt medical hospital, pune Amgen The above changes in the protocol may be circulated as soft copy to committee members for their remarks. The risk versus benefit of the test drug combination in mild hypertension as a first line therapy is not justified. The purpose of the study is to evaluate a fixed dose combination blood pressure lowering pill (Triple Pill) based strategy as a first line therapy compared to usual care among individuals with mild to moderate hypertension on no or minimal drug therapy with step care therapy. It is not an unmet need. After detailed deliberation, the NDAC opined that at present there is no scientific justification for the use of three drugs combination pill as starting/ first line therapy in stage I hypertension/ mild hypertension. Investigators suggested to submit the published documents on this specific issue of triple drug therapy, as first line approach in mild hypertension. The committee opined that the submitted documents should be forwarded to cardiologist for their the opinion. Cardiologist opinion may be circulated as soft copy to rest of the members for their remarks. The applicant did not come for presentation The risk vs benefit profile of the IMP from preclinical pharmacology, single dose and repeat dose toxicity studies and phase I and II clinical trials justify the conduct of this study.

4 10. CT/344/08 UT-15C (Treprostinil diethanolamine) ICON The purpose of the study is to assess the impact of additional LDL-Cholesterol reduction on major CV events when study drug is used in combination with statin therapy in patients with clinically evident CV disease. The test drug may potentially provide alternative treatment option for cardiovascular disease. The firm presented the protocol amendment version 04.After detailed deliberation the committee opined that the protocol amendment is acceptable. However, the committee did not recommend the increase in age limit from 80yrs to 85 yrs. Accordingly the revised protocol shall be submitted by the firm to this directorate for the official approval. The risk vs benefit profile of the study drug from preclinical pharmacology, single dose and repeat dose toxicity studies and several clinical trials justify the conduct of this study. The purpose of the study is to assess the long term safety of the study drug in the patients who participated in previous clinical trials of this study drug. The test drug may potentially provide alternative treatment option for pulmonary arterial Hypertension. The firm initially presented the protocol amendment version 05 in the NDAC held on wherein the committee recommended that the safety data be presented for the SR formulation. The firm now made a presentation regarding

5 the protocol amendment 05. However, company could not justify any scientific basis for administering the drug in TID doses in place of BID. Therefore committee did not recommend this amendment. 11. CT/12/14 Ticagrelor /Cadila/11-BD Peg EPO M/s Atrazeneca pharma M/s Cadila Healthcare Single and repeat-dose toxicity studies in mice, rats and marmosets and Phase I, II and III clinical studies justify the conduct of the proposed phase IIIb study. The objective of the study is to compare the effect of long term treatment with study drug vs placebo for the prevention of major cardiovascular events in patients with Type 2 diabetes at high risk of CV events. The test drug may provide potential benefit due to its anti-platelet action for prevention of CV events in patients with TDM who has no medical history of previous MI or stroke. The firm made a presentation and requested for waiver of upper age limit. The committee opined that the unlimited age for recruitment may pose a potential risk since there is no evidence of safety in the older subset of the targeted diabetic population with the trial drug. Committee finally recommended the conduct of the trial subject to the condition that there is an upper age limit for recruitment that is 75 years and the revised protocol should be submitted to CDSCO before permitting the trial. Firm presented the results of Part A of the Phase I/II study with their indigenously developed drug product (Peg EPO) & requested for approval of initiation of Part B of the already approved Phase I/II study. Committee after reviewing the proposal, recommended the continuation of the Part B of the already approved Phase I/II study with inclusion of following in study protocol:

6 Range of egfr should be between ml/min Include Predialysis patients only If Haemoglobin falls below 6.5gm or more than 2gm, then patients will be out of the study and standard of care will be provided. Accordingly firm should submit the revised protocol in compliance to above said recommendation to this office.