Approval Letter Other 211566 (Jan 1, 2024)

Summary

This document contains two FDA letters concerning NDA 211566 for Sitagliptin Tablets. The first letter, dated March 3, 2023, details extensive requirements for updating safety data in a resubmission, including incorporating new clinical trial data, comparing adverse event frequencies, providing worldwide safety experience, and translating foreign labeling. It mandates resubmission or other actions within one year. The second letter, dated September 2, 2021, grants tentative approval for Sitagliptin Tablets for type 2 diabetes, contingent on the resolution of patent protection and exclusivity issues, specifically a patent infringement suit related to a Paragraph IV certification. It outlines the conditions for lifting the 30-month stay and the process for requesting final approval, which includes a safety update and confirmation of any changes to the application's conditions.

Key points

• Describe in detail any significant changes or findings in the safety profile.
• Incorporate new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
• Present tabulations of new safety data combined with the original application data.
• Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies.
• For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in clinical trials.
• Present a retabulation of the reasons for premature trial discontinuation by incorporating drop-outs from newly completed trials and describe any new trends or patterns identified.
• Provide case report forms and narrative summaries for each subject who died during a clinical trial or who did not complete a trial because of an adverse event, and for serious adverse events.
• Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data.

Cited reasons

• Adverse Event Tables for Other Indications
• Missing Case Report Forms and Narratives
• Updated Clinical Exposure Information
• Worldwide Safety Experience Summary
• English Translations of Foreign Labeling
• The application lacks comprehensive and adequately presented safety data, including specific adverse event tables for other indications, complete case report forms and narratives for serious adverse events, updated clinical exposure information, and a summary of worldwide safety experience. Additionally, English translations of all approved foreign labeling are required.

Recommended actions

• Describe in detail any significant changes or findings in the safety profile.
• Incorporate new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
• Present tabulations of new safety data combined with the original application data.
• Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies.
• For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in clinical trials.
• Present a retabulation of the reasons for premature trial discontinuation by incorporating drop-outs from newly completed trials and describe any new trends or patterns identified.
• Provide case report forms and narrative summaries for each subject who died during a clinical trial or who did not complete a trial because of an adverse event, and for serious adverse events.
• Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data.

Deficiency summary

The application lacks comprehensive and adequately presented safety data, including specific adverse event tables for other indications, complete case report forms and narratives for serious adverse events, updated clinical exposure information, and a summary of worldwide safety experience. Additionally, English translations of all approved foreign labeling are required.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2) NDA

Impact

Impact score

0.95

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application requires substantial updates to its safety data presentation, including detailed clinical trial information, worldwide safety summaries, and complete translations of foreign labeling, to achieve final approval.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%