An adaptive seamless Phase 2-3 design with multiple endpoints.

Abstract

Adaptive seamless Phase 2-3 design has been considered as one possible way to expedite development time for a drug program by allowing the expansion from an ongoing Phase 2 trial into a Phase 3 trial. Multiple endpoints are often tested when a regulatory approval is pursued. Here we propose an adaptive seamless Phase 2-3 design with multiple endpoints which can expand an ongoing Phase 2 trial into a Phase 3 trial based on an intermediate endpoint for adaptive decision and test the endpoints with a powerful multiple test procedure. It is proved that the proposed design can preserve the familywise Type I error under a mild assumption that is expected to hold in practical considerations. We illustrate our proposed design with an example trial design for oncology. Simulations are conducted to confirm the control of the familywise Type I error and the adaptive seamless Phase 2-3 design is illustrated with an example.