Effect of Food on the Pharmacokinetics of a Combination of Olanzapine and Samidorphan

ALKS 3831 is a combination of olanzapine and samidorphan (OLZ/SAM), intended to provide the antipsychotic efficacy of OLZ while mitigating its known weight gain and metabolic effects. This randomized, 2‐way crossover study evaluated the effect of food on the pharmacokinetics (PK) of OLZ and SAM (both are Biopharmaceutics Classification System class 3 compounds) given in combination as OLZ/SAM. Thirty‐six healthy volunteers were randomized to receive a single dose of OLZ/SAM (10 mg OLZ/10 mg SAM) in either fasted or fed conditions. After a 14‐day washout period, study participants received the same OLZ/SAM dose in the opposite condition. PK profiles of OLZ and SAM were similar in fed and fasted conditions. The 90% confidence intervals (CIs) for the fed/fasted ratio of the geometric means for OLZ AUC 0‐∞ and C max and SAM AUC 0‐∞ were within the equivalence limit of 80%‐125%. Although the lower bound of the 90%CI for the fed/fasted ratio of SAM C max (76%‐94%) was slightly below the 80% equivalence limit, this slight decrease was not considered clinically meaningful. The results indicated that food does not have a clinically relevant impact on the PK of OLZ and SAM given as OLZ/SAM.