The following is a summary of “Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial,” published in the July 2023 issue of Endocrinology & Metabolism by Miller, et al.

Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region. It is characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia, which can lead to severe obesity if not controlled.

For a study, researchers sought to investigate the effect of diazoxide choline extended-release tablets (DCCR) on hyperphagia in individuals with PWS. Additional endpoints assessed included Global Impression Scores and changes in body composition, behaviors, and hormones.

In the DESTINY PWS trial, a phase 3 trial with a 13-week duration, 127 participants aged 4 years and older with PWS and hyperphagia were randomly assigned in a 2:1 ratio to receive either DCCR or placebo in a double-blind, placebo-controlled manner.

The analysis showed that DCCR did not result in a significant improvement in hyperphagia based on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) scores (least-square mean [SE] -5.94 [0.879] vs -4.27 [1.145]; P = .198). However, it did show significant improvements in hyperphagia for participants with severe baseline hyperphagia (LSmean [SE] -9.67 [1.429] vs -4.26 [1.896]; P = .012). Two of three secondary endpoints showed improvement (Clinical Global Impression of Improvement [CGI-I]; P = .029; fat mass; P = .023). The pre-COVID analysis also demonstrated improvements in all primary (HQ-CT; P = .037) and secondary endpoints (CGI-I; P = .015; Caregiver Global Impression of Change; P = .031; fat mass; P = .003). DCCR treatment was generally well-tolerated, with no significant differences in treatment-emergent adverse events between the DCCR and placebo groups (83.3% vs 73.8%).

Although the primary analysis did not significantly improve hyperphagia with DCCR, the treatment showed positive effects in participants with severe baseline hyperphagia and in the pre-COVID analysis. Additionally, DCCR was associated with significant improvements in body composition and clinician-reported outcomes.

Source: academic.oup.com/jcem/article/108/7/1676/6987298