Bioequivalence of Olanzapine Given in Combination With Samidorphan as a Bilayer Tablet (ALKS 3831) Compared With Olanzapine‐Alone Tablets: Results From a Randomized, Crossover Relative Bioavailability Study

The objective of this study was to evaluate the relative bioavailability of olanzapine in 3 olanzapine‐containing tablet formulations. ALKS 3831 is a fixed‐dose combination of olanzapine (OLZ, an atypical antipsychotic) and samidorphan (SAM, a μ‐opioid receptor antagonist with low intrinsic activity at δ‐ and κ‐opioid receptors), intended to provide the efficacy of OLZ while mitigating its known weight and metabolic effects. Relative bioavailability of OLZ in ALKS 3831, a bilayer tablet containing OLZ and SAM, a matching bilayer tablet containing OLZ only (OLZ), and Zyprexa (brand olanzapine [B‐OLZ]) was assessed in an open‐label study. Forty‐eight healthy volunteers were randomly assigned to receive single oral doses of ALKS 3831 (10 mg OLZ/10 mg SAM), OLZ (10 mg OLZ), and B‐OLZ (10 mg B‐OLZ) on day 1 of each treatment period. Blood samples for pharmacokinetic evaluation were collected before and after each dose. Ratios of OLZ AUC(0‐∞), AUC(0‐t), and C(max) were compared between treatments and tested for bioequivalence, determined by 90%CIs of the geometric mean ratios (GMRs). GMRs of OLZ AUC(0‐∞), AUC(0‐t), and C(max) were close to 1, and the 90%CIs of the GMRs were contained within the bioequivalence limit of 80%–125% for comparison of ALKS 3831 with B‐OLZ, ALKS 3831 with OLZ, and OLZ with B‐OLZ, demonstrating bioequivalence of OLZ in ALKS 3831, OLZ, and B‐OLZ.