Seamless Adaptive Designs in Early Phase Drug Development

• Activity Number: 429
• Type: Invited
• Date/Time: Wednesday, August 6, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Vlad Dragalin*+
• Companies: Aptiv Solutions
• Keywords: adaptive design ; dose escalation ; dose finding ; dose ranging ; proof of concept ; seamless Phase I/II

Abstract

This talk will focus on one type of adaptive design, applied on the program level of a compound that achieves efficiency by combining in a single trial, objectives that are usually addressed in two separate conventional studies. Such a strategy provides the obvious benefit of reducing the timeline by running the two studies seamlessly under a single protocol with the same clinical team and the same centers and achieves trial efficiency by combining the information from subjects in both studies in the final analysis. Other examples include (i) combining a conventional multiple ascending dose escalation in patients and proof of concept in a single trial, (ii) combining the proof of concept with the dose ranging study, by starting the study with equal randomization of patients to the top dose and placebo and then opening enrollment to other doses of the compound only if a futility rule is over passed, (iii) seamless Phase II/III adaptive designs, by starting a confirmatory trial with couple of doses of the new compound with a pre-planned option of selecting the "best" dose for the second stage of the trial.