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 AUC0-∞, AUC0-t, and Cmax were compared between treatments and tested for bioequivalence, determined by 90%CIs of the geometric mean ratios (GMRs). GMRs of OLZ AUC0-∞, AUC0-t, and Cmax 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.