Back to Explorer

Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control Guidance for Industry

DraftCenter for Drug Evaluation and Research03/10/2020

Description

The purpose of this guidance is to provide the Food and Drug Administration’s (FDA’s) current recommendations regarding the overall evaluation of safety for the development of drugs and biologics indicated for improvement of glycemic control in patients with type 2 diabetes mellitus. The recommendations in this guidance reflect discussions at the Endocrinologic and Metabolic Drugs Advisory Committee meeting held October 24–25, 2018, that considered FDA’s review of cardiovascular (CV) outcome trials (CVOTs).

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

2
Antidiabetic drug

New drugs intended to improve glycemic control.

Biologics

Products for which batch/lot information is particularly important

Stakeholders

2
Data safety monitoring boards

Independent committees providing oversight of safety findings.

Pharmaceutical Sponsors

Entities involved in drug development and discussion with FDA

Regulatory Context

Regulatory Activities

3
Phase 3 clinical trials

Adult trials that should include adolescent participants.

Marketing application

Submission for drug approval

Postmarketing Requirements

PMRs required by FDA; Studies or clinical trials conducted by the applicant after FDA approval

Document Types

1
Safety Database

Collection of safety data needed to support drug approval

Attributes

2
Stage 3/4 chronic kidney disease

Specific severity of kidney disease required in the safety database.

4,000 patient-years

Minimum exposure requirement in phase 3 clinical trials.

Technical Details

Testing Methods

2
Adjudication

Rigorous method for assessing adverse CV events.

Cardiovascular Outcome Trials

Trials used to evaluate cardiovascular risk in antidiabetic therapies

Clinical Concepts

10
Adverse CV outcomes

Important source of morbidity and mortality to be monitored.

Peripheral vascular disease

Specific example of established CV disease.

Stroke

correlated with female sex in VAD study

Myocardial infarction

For studies in which the outcome or outcomes of interest (e.g., myocardial infarction or stroke) include fatal outcomes.

CV disease

Cardiovascular disease, a common complication in the target population.

Chronic kidney disease

Condition requiring dietary restriction of sodium, potassium, or phosphorus

Ischemic CV Events

Specific cardiovascular safety outcomes monitored in trials

Cardiovascular Risk

Safety concern evaluated in antidiabetic drug development

Glycemic Control

therapeutic intent of the medical devices

Type 2 Diabetes Mellitus

major comorbidities associated with excess adiposity; Common weight-related comorbidity

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control Guidance for Industry | Guideline Explorer | BioRegHub