Evaluation of an Adaptive Maximizing Design Study Based on Clinical Utility Versus Morphine for TRV130 Proof-of-Concept and Dose-Regimen Finding in Patients With Postoperative Pain After Bunionectomy.

Background: Conventional opioids provide powerful analgesia but also produce efficacy-limiting adverse effects, limiting their clinical utility (CU). TRV130 is being evaluated to determine whether CU can be expanded by way of increased efficacy, decreased adverse effects, or some combination thereof.
Methods: This phase 2 study of TRV130 blends traditional objectives with novel design features aimed toward the specific strategic goal of optimizing the attributes of TRV130 efficacy and tolerability compared with the conventional opioid, morphine. The adaptive maximizing design (AMD) was developed to maximize assignment of future patients to doses that demonstrate maximum balance between efficacy and tolerability (ie, CU) assessed via a CU function.
Results: Our evaluation of the AMD performance characteristics reveals that the AMD has a strong capacity to estimate the TRV130 dose-regimens with maximum CU, assign more patients to the TRV130 dose-regimens with maximum CU, and, conversely, assign fewer patients to doses away from the those with maximum or near-maximum CU.
Conclusions: Based on this evaluation of performance characteristics of the AMD versus a traditional study design, the AMD was selected for this proof-of-concept and dose-regimen finding study of TRV130.