Case Study: Design Considerations for a Phase Ib Randomized, Placebo-Controlled, 4-Period Crossover Adaptive Dose-Finding Clinical Trial

Abstract

A new formulation of a test drug was to be studied in patients for the first time. Preclinical studies yielded a wide range of effective doses across species, so there was a desire to include at least 6 doses in the dose-finding trial. Adaptive design was chosen to focus the dose assignments on those that yielded at least 75 % of maximal response (ED75). A 4-period crossover in which each of 68 patients received 3 doses of test drug and placebo was chosen since it optimized performance characteristics. Frequent interim analyses were performed to optimally choose the 3 doses of test drug to maximize dose assignments to the doses estimated to be closest to ED75 based on analysis of study data accumulated up to each interim analysis time. The completed study yielded minimal assignment of doses away from ED75 and successfully identified, and focused dose assignment around, the target dose. The table below shows the numbers of assignments to each dose and the respective observed mean responses.

	Dose1(Pbo)	Dose2	Dose3	Dose4	Dose5	Dose6	Dose7
N	67	42	0	30	66	25	36
Mean	3	7	n/a	13	10	9	12