The NK3 Receptor Antagonist ESN364 Suppresses Sex Hormones in Men and Women.

Context: Women's health disorders are commonly treated by agents that suppress the hypothalamic-pituitary-gonadal axis. NK3 receptor antagonism modulates this axis with distinct pharmacology compared to existing therapies. Objective: The study aim was to evaluate safety, pharmacokinetics, and pharmacodynamics on gonadotropins and sex hormones after single- and multiple-dose administration of an NK3R antagonist to healthy men and women. Design and Setting: This was a first-in-human, double-blind, placebo-controlled, combined single and multiple ascending dose trial. Participants: Forty-one men and 24 regularly cycling women participated in the study. Intervention(s): In part 1 of the study, men received single oral doses of 3–180 mg or placebo. In part 2, men received placebo or 20, 60, or 180 mg each day for 10 days. In part 3, women received placebo or 20, 60, or 180 mg each day for 21 days, where dosing was initiated on day 3 ± 2 after menses. Main Outcome Measure(s): Safety, tolerability, pharmacokinet...