Endocrine Abstracts

Background: PWS is a rare genetic neurodevelopmental disorder characterized by hyperphagia, obesity, hormonal deficiencies, and problem behaviors for which there is no approved treatment. DESTINY PWS (C601) was an international, placebo-controlled, Phase 3 study of DCCR (diazoxide choline) extended-release tablet in participants with PWS, age 4 and older with hyperphagia. C602 is a long-term, open label extension to C601. DCCR administration to participants with PWS in these studies resulted in significant improvements in hyperphagia, behavior, body composition and metabolic markers. Significant improvements in hyperphagia and PWS associated behaviors were observed in a comparison of results from C601 and C602 to data from a cohort of participants in a PWS natural history study.

Objective: In order to further confirm the effects of DCCR administration on hyperphagia and other endpoints in a controlled setting, a randomized withdrawal (RW) period has been initiated for participants enrolled in C602. All have received DCCR for more than 2 years. The goal is to supplement the currently available data with further controlled data to support a regulatory filing. Input into the design, conduct and analysis of the RW period were sought from patients and caregivers, clinicians and from the FDA.

Methods: Participants who are currently enrolled in C602 will be consented to participate in a 16-week RW period and will be randomized 1:1 to DCCR or placebo. Following completion of the RW period, participants will be eligible to enroll in a new open-label study (C614). Participants who do not consent to the RW period will be eligible to enroll in C614 following 16 weeks off treatment. The primary endpoint of the RW period is change from baseline in Hyperphagia Questionnaire for Clinical Trials total score. Secondary endpoints include the Clinical Global Impression of Improvement (CGI-I), and the Clinical Global Impression of Severity (CGI-S). Each endpoint will be assessed at baseline (except CGI-I which measures improvement from baseline) and at 4, 8, 12 and 16 weeks. Additional endpoints include changes in other PWS-associated behaviors as assessed by the Prader-Willi Syndrome Profile Questionnaire, weight and BMI, a set of CGI-S of various PWS behaviors and assessments by the Caregiver Global Impression of Severity and Change. The Baseline and 16-week visit are in-clinic, all others are telemedicine. Safety monitoring will occur as it was in C602.