14 th SEC- Gastroenterology& Hepatology held on at CDSCO (HQ), FDA Bhawan, Kotla road, NewDelhi

Transcription

1 14 th SEC- Gastroenterology& Hepatology held on at CDSCO (HQ), FDA Bhawan, Kotla road, NewDelhi Recommendation:- The 14 th SEC ( Gastroenterology& Hepatology) meeting deliberated the proposals on and recommended the following:- S.No Global Clinical Trial Proposal 1 CT/16/15 M/s Roche Pegylated Interferon alfa-2a The proposed trial is a phase IIIb, randomized openlabel study of 8-week lamivudine followed by 48 weeks of interferon vs no treatment in children aged 3-17 years with immune tolerant hepatitis B virus infection (HBsAg and HBeAg positive for 6 months, HBV DNA >2000 IU/mL, normal ALT on 3 occasions). The committee deliberated the proposal and raised the following concerns: 2 CT/39/14 Masitinib M/s Clinicals Maya a. Lamivudine has a high propensity to lead to drug resistance. This risk is particularly high in those with high viral load, as is seen in children with immune tolerant phase. b. In children with lower viral load, the need for treatment itself may be weaker, because their natural history is milder. c. The study is proposed to be done in children with a broad age range (3-17 years). In younger age groups, safety concerns would be higher. Hence, this protocol is not approved in this form at this stage. Dr. Shobhna Bhatia, one of the proposed investigators, did not participant in decision making process.. The proposal was deliberated in SEC on 10/07/15. The firm was not able to present the safety data from non-oncology trials. Hence committee recommended re-deliberating the same. The firm now presented the break -up of AEs and SAEs from non oncology trials with this molecule, after detailed deliberation the committee opined that the safety and efficacy data from phase II study in crohn s disease is inadequate to support the proposed phase III trial at this stage. Hence the committee did not recommend the conduct of the trial.

2 New Drug Division Proposal /15-DC M/s. Hetero The firm presented the proposal for permission to Sofosbuvir + Labs Limited manufacture and market, with waiver of local clinical Ledipasvir tablets trial for a fixed-drug combination of sofosbuvir and (400mg+90mg ) ledipasvir, for treatment of chronic hepatitis C (CHC) genotype 1 in adults. A perusal of the documents provided indicates that the above fixed-drug combination is approved by US FDA and Health Canada for treatment of chronic hepatitis C virus (CHC) genotype 1 infection in adults. The permission requested is for an indication for which it is already approved in other countries. The currently available treatments for genotype 1 HCV infection (interferon -ribavirin combination, or sofosbuvir-interferon-ribavirin comination) are not effective in some such patients, and their use is not possible in some subgroups of patients, such as those with renal failure, prior organ transplantation, decompensated liver disease. In these patients, there is a need for this combination. Hence, the Committee felt that there may be a point in permitting marketing of the drug with waiver of local clinical trial subject to the following conditions: a. That a bioequivalence study will be carried out. b. The prescribing information, patient information sheet and all the material used for marketing will clearly indicate that the drug combination is not approved for treatment of infection with non-1 HCV genotypes. c. The firm will undertake a phase IV clinical trial, the protocol of which should be submitted. However, the committee took cognizance of the order dated July 3, 2014, that waiver of clinical trial in Indian population for approval of new drug, which have already been approved outside India, can presently be considered only in cases of national emergency, extreme urgency, and epidemic and for orphan drugs for rare diseases and drugs indicated for conditions/diseases for which there is no therapy.

3 The drug does not meet any of the situations listed above. Hence the committee did not recommend waiver of the need for a local trial /15-DC(Pt-A) Sofosbuvir + Ledipasvir tablets (400mg+90mg ) /15-dc Daclatasvir M/s Mylan M/s Natco The firm presented the proposal for permission to manufacture and market, with waiver of local clinical trial for a fixed-drug combination of sofosbuvir and ledipasvir, for treatment of chronic hepatitis C (CHC) in adults. During the presentation, the company informed that the combination is already approved for the treatment of chronic hepatitis C. A perusal of the documents provided indicates that the above fixed-drug combination is approved by US FDA and Health Canada for treatment of chronic hepatitis C virus (CHC) genotype 1 infection in adults. Hence, the permission requested is for an indication that extends beyond the indication for which it is approved in other countries. Hence, the committee did not recommend marketing of the drug with waiver of local clinical trial. The firm presented the proposal for permission to manufacture and market daclatasvir, with waiver of local clinical trial for treatment of chronic hepatitis C (CHC) in adults, in combination with other medicinal products. The drug is already approved in combination with other medicinal products for the treatment of chronic hepatitis C infection in adults. The available data show that the drug has activity against various genotypes of HCV, and is safe, except severe bradycardia when administered along with amiodarone. The Committee felt that there may be a point in permitting marketing of the drug with waiver of local clinical trial subject to the following conditions: a. That a bioequivalence study will be carried out. b. The firm will undertake a phase IV clinical trial, the protocol of which should be submitted. However, the committee took cognizance of the order dated July 3, 2014, that waiver of clinical trial in Indian population for approval of new drug, which

4 have already been approved outside India, can presently be considered only in cases of national emergency, extreme urgency, and epidemic and for orphan drugs for rare diseases and drugs indicated for conditions/diseases for which there is no therapy. The drug does not meet any of the situations listed above. Hence the committee did not recommend waiver of the need for a local trial /14-DC(Pt-B) Acotiamide Hydrochloride 100mg tablets M/s Hetero labs The firm has requested for permission to undertake a phase III, randomized clinical trial of acotiamide in patients with dyspepsia due to post-prandial distress syndrome, using mosapride as a comparator drug. The committee deliberated the proposal and recommended the conduct of the phase III trial and bioequivalence study /2014-DC(Pt DRL-Add Strength Omeprazole magnesium 10mg delayed release granules for oral suspension SND Division Proposal M/s Dr Reddy s Laboratories The firm has requested for permission to market a granule formulation of omeprazole 10 mg in adult patients with gastroesophagesl reflux disease for maintenance purposes, and for children <20 Kg for treatment. The Committee noted that omeprazole 10 mg tablet is already approved by DCGI in adults, and the firm has stated that they have conducted a bioequivalence study with their proposed formulation vis-à-vis similar formulation approved in USA (omeprazole 10 mg delayed release oral suspension). Fixed Dose Combination /10-DC(pt TIL) Streptococcus M/s India faecalis T-110 JPC+Clostridium butyricumto-a + Bacillusmesentericu s TO-A JPC + Lactobacillus sporogenes Tablet The committee opined that the proposed formulation can be approved for adults. However, the firm is required to conduct a phase 3 clinical trial in children <20 Kg before consideration of this drug for marketing approval in this group. Accordingly, the firm shall submit the trial protocol. The firm did not come for presentation.

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