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-infinity) and C-max and SAM AUC(0-infinity) 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.