The following is a summary of “Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial,” published in the July 2023 issue of Endocrinology & Metabolism by Roof, et al.
For a randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up, researchers sought to evaluate the safety and efficacy of intranasal carbetocin as a selective oxytocin replacement therapy in individuals with Prader-Willi syndrome (PWS). PWS is a rare genetic disorder characterized by endocrine and neuropsychiatric issues, including hyperphagia, anxiousness, and distress.
The study was conducted at 24 ambulatory clinics at academic medical centers. A total of 130 participants with PWS between the ages of 7 and 18 years were included in the trial. Participants were randomly assigned to receive 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or a placebo three times daily during an 8-week placebo-controlled period (PCP). During the subsequent 56-week long-term follow-up period, participants initially on placebo were randomly assigned to receive either 9.6 mg or 3.2 mg carbetocin, while those who received carbetocin during the PCP continued with their previous dose.
The primary endpoints of the study assessed changes in hyperphagia (evaluated using the Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (assessed using the Children’s Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for the 9.6 mg carbetocin group compared to the placebo group. The first secondary endpoints examined these same outcomes for the 3.2 mg carbetocin group compared to the placebo group. Additional secondary endpoints included assessments of anxiousness and distress behaviors (measured by the PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C).
Due to the onset of the COVID-19 pandemic, enrollment in the trial was stopped prematurely. The primary endpoints showed numerical improvements in both HQ-CT and CY-BOCS scores, but these improvements were not statistically significant. However, the 3.2-mg carbetocin group demonstrated nominally significant improvements in HQ-CT, PADQ, and CGI-C scores compared to the placebo group. The improvements were sustained during the long-term follow-up period. The most common adverse event observed during the PCP was mild to moderate flushing.
Intranasal carbetocin was well tolerated, and the 3.2-mg dose showed clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in individuals with Prader-Willi syndrome (PWS).