Регуляторные исследования и экспертиза лекарственных средств (Feb 2018)
Possibilities of adaptive design implementation in clinical trials of next-in-class drugs
Abstract
The article investigates the possibility of streamlining the methodology of clinical studies of next-in-class drugs by implementing an adaptive design. Next-in-class drugs are original drugs with known biological targets, similar in structure and mode of action to already existing well-established innovative products. The results of phase II-III clinical trials are illustrated by three investigational products of different pharmacological classes, including a DPP-4 inhibitor (Diabetes mellitus type 2), factor Xa inhibitor (VTE prevention in orthopedic surgery), and NNRTI (HIV). A two-stage «seamless» adaptive design was developed for the clinical trials. In all the three studies the non-inferiority hypothesis was tested versus the standards of care. The adaptive design in DPP-4 inhibitor study made it possible to assess the efficacy and safety of two consecutive treatment regiments (mono- and combination therapy). The optimal doses for factor Xa inhibitor and NNRTI were selected at Stage 1, and their efficacy and safety were tested at Stage 2. The non-inferiority vs. standards of care was successfully demonstrated for all investigational products. The introduction of the adaptive design resulted in the optimization of the clinical programs of the next-in-class drugs.
