First‐in‐Human Study of Merotocin, a Short‐Acting Peptidic Oxytocin Receptor Agonist for Lactation Support

Endogenous oxytocin plays an important role in lactation, but its effectiveness as an exogenous galactagogue has been modest due to dose-limiting side effects related to off-target effects at the vasopressin V2 receptor. Merotocin (FE 202767) is a short-acting peptidic oxytocin receptor agonist with the potential to aid mothers experiencing preterm delivery and inadequate milk production by increasing their milk volume. A first-in-human, single-center, randomized, placebo-controlled study investigated single and repeated intranasal administrations (every 3 hours) at doses from 5 to 400 µg and intravenous administration at 20 µg in healthy, nonpuerperal women. Pharmacokinetic parameters were determined after all doses. Bioavailability was determined after crossover intranasal and intravenous administrations. Merotocin was rapidly absorbed and eliminated after intranasal administration, median time to maximum plasma concentration was approximately 15 minutes, and the terminal half-life was approximately 30 minutes. No accumulation was seen. Merotocin was not detected in urine, and metabolites were not detected in either plasma or urine, indicating elimination independent of the kidneys. Systemic bioavailability of merotocin after intranasal administration is low. All doses were tolerated, with few adverse events (mostly headache), all mild intensity. A maximum tolerated intranasal dose was not identified in this study. Intranasal administration of merotocin at doses up to 400 µg was tolerated by healthy women, and the pharmacokinetic and safety profiles support frequent repeated administration expected in lactation clinical practice.