CONTEXT
Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy.
OBJECTIVE
To evaluate safety and efficacy of intranasal carbetocin in PWS.
DESIGN
Randomized double-blind placebo-controlled phase 3 trial with long-term follow-up.
SETTING
25 ambulatory clinics at academic medical centers.
PARTICIPANTS
130 participants with PWS aged 7-18.
INTERVENTIONS
Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo TID during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up (LTFU) period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their prior dose.
MAIN OUTCOME MEASURES
Primary endpoints assessed change in hyperphagia (HQ-CT) and obsessive-compulsive symptoms (CY-BOCS) during the PCP for 9.6 mg versus placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg versus placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PADQ) and clinical global impression of change (CGI-C).
RESULTS
Due to onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS scores which were not statistically significant; however, the 3.2 mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs. placebo. Improvements were sustained in the LTFU period. The most common adverse event during the PCP was mild to moderate flushing.
CONCLUSIONS
Carbetocin was well tolerated, and the 3.2 mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS.