Pharmacokinetic Interactions Between Ethanol and PT150, a Selective Glucocorticoid Receptor Antagonist, in Healthy Volunteers.

OBJECTIVES

PT150, a novel competitive glucocorticoid receptor antagonist, is hypothesized to be a potential treatment for alcohol use disorder, with safety studies as an important first step for medication development. We aimed to assess PT150 safety and tolerability, including impact on pharmacokinetics when administered concomitantly with ethanol in healthy participants.

METHODS

This nonrandomized, single-site, drug-drug interaction study of PT150, coadministered with oral ethanol (alcohol beverage), was conducted at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, TX. Participants, each of whom received the same exposure sequence and served as their own control, were healthy, alcohol-experienced volunteers aged 21-64 years. Blood samples were obtained before and after 1.03 mL/kg ethanol exposure, before and after the fifth dose of PT150 (900 mg/d), and again before and after a sixth dose of PT150 (900 mg/d) administered with 1.03 mL/kg of ethanol. The primary pharmacokinetic outcomes included differences in peak plasma concentrations ( Cmax ), time to reach peak plasma concentrations ( tmax ), terminal elimination half-life ( t1/2 ), and area under the concentration-time curve (AUC) of PT150 alone and in combination with ethanol.

RESULTS

There was no statistically significant evidence that coexposure to ethanol impacted PT150 pharmacokinetics, and no statistically significant evidence that coexposure to PT150 impacted ethanol pharmacokinetics. There were no clinically significant abnormal electrocardiograms or serious adverse events.

CONCLUSIONS

These data suggest that coadministration of PT150 and alcohol does not produce significant pharmacokinetic interactions, supporting the feasibility of evaluating PT150 in future clinical trials for alcohol use disorder.