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Clinical Trial
. 2012 Nov 1;6(6):1319-27.
doi: 10.1177/193229681200600610.

An adaptive, dose-finding, seamless phase 2/3 study of a long-acting glucagon-like peptide-1 analog (dulaglutide): trial design and baseline characteristics

Mary Jane Geiger  1 , Zachary Skrivanek, Brenda Gaydos, Jenny Chien, Scott Berry, Donald Berry
Affiliations
Clinical Trial

An adaptive, dose-finding, seamless phase 2/3 study of a long-acting glucagon-like peptide-1 analog (dulaglutide): trial design and baseline characteristics

Mary Jane Geiger et al. J Diabetes Sci Technol. .

Abstract

Dulaglutide (dula, LY2189265) is a once-weekly glucagon-like peptide-1 analog in development for the treatment of type 2 diabetes mellitus. An adaptive, dose-finding, inferentially seamless phase 2/3 study was designed to support the development of this novel diabetes therapeutic. The study is divided into two stages based on two randomization schemes: a Bayesian adaptive scheme (stage 1) and a fixed scheme (stage 2). Stage 1 of the trial employs an adaptive, dose-finding design to lead to a dula dose-selection decision or early study termination due to futility. If dose selection occurs, the study proceeds to stage 2 to allow continued evaluation of the selected dula doses. At completion, the entire study will serve as a confirmatory phase 3 trial. The final study design is discussed, along with specifics pertaining to the actual execution of this study and selected baseline characteristics of the participants.

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Figures

Figure 1
Figure 1
Adaptive seamless phase 2/3 study design. AWARD-5 is a double-blind randomized, placebo-controlled, adaptive, dose-finding, inferentially seamless phase 2/3 study. Two randomization schemes are used which divide the study into two stages: adaptive randomization (stage 1) and fixed randomization (stage 2). Seven doses of dula will be evaluated in stage 1 along with comparators. Patients will be adaptively allocated across these doses based on accumulating data. The decision point is defined as the time when sufficient information has accrued to either select dula doses or to stop the trial. If dose selection occurs, stage 2 will begin. Only patients assigned the selected doses and comparators will continue to be followed; all others will stop further participation in the trial. Additional patients will enroll and be assigned to the comparators or dula. Patients will be followed for 24 months and complete a safety visit 30 days after drug discontinuation.
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