Phase 1 Study in Japanese Subjects (NCT04823208)

Study Overview

This Phase 1 study (NCT04823208) was designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of retatrutide in Japanese adults with type 2 diabetes. It ran from May 2021 to June 2022 at four sites in Japan and enrolled 64 participants. Bridging studies in Japanese populations are a regulatory requirement for the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, as pharmacokinetic parameters and tolerability can differ across ethnic groups.

Study Design

Design

Randomized, placebo-controlled, multiple-ascending dose trial (weekly injections of retatrutide or placebo; up to about 5 months per participant including screening).

Population

Japanese adults aged 20-70 years with type 2 diabetes.

Objectives

1. Characterize the pharmacokinetic profile of retatrutide in Japanese subjects
2. Assess safety and tolerability at escalating doses
3. Compare PK parameters with data from Western populations
4. Support the regulatory pathway for approval in Japan

Significance

This study is part of Eli Lilly’s global development strategy for retatrutide. Japan represents one of the largest pharmaceutical markets globally, and the PMDA requires ethnic bridging data before approving drugs that were primarily developed in Western populations. The study results inform whether dose adjustments are necessary for Japanese patients.

Regulatory Context

Japan has its own obesity treatment guidelines and lower BMI thresholds for defining obesity (BMI ≥25 vs. ≥30 in Western guidelines). The results of this study, combined with the global Phase 3 program data, will be included in the Japanese regulatory submission package.