OR35-07 The Glycemic Outcomes of Diazoxide Choline Extended-Release (DCCR) Tablets for Administered for Hyperphagia in Individuals with Prader-Willi Syndrome Over 4 Years

Abstract

Objectives: To characterize the glycemic outcomes in clinical trial participants with Prader-Willi Syndrome (PWS) during administration of diazoxide choline extended-release (DCCR) when administered over 4.5 years. Methods: PWS is a rare genetic neurobehavioral metabolic disorder characterized by hyperphagia. People living with PWS are at high risk of developing impairment of glycemic control and diabetes. DCCR is an oral, once-daily medication under development for amelioration PWS symptoms including hyperphagia. We analyzed data for participants who received DCCR across 2 Phase 3 studies (C601 - a randomized controlled trial of DCCR vs placebo, and C602 OLE- an open label extension of DCCR for subjects who had completed C601). The analyses included 125 participants who received DCCR in any study period. Participant glycemic status was monitored with adverse event (AE) reporting and laboratory testing including HbA1c. Results: Mean duration of DCCR exposure was 131.5 weeks, with a maximum duration of 237.3 weeks. Fifty-two percent of participants exceeded 3 years of exposure. At C601 baseline 7.9% of participants were administered glucose lowering medications. At DCCR baseline, before starting DCCR, mean (SD) HbA1c% was 5.55 (0.41). Adverse events of hyperglycemia were reported by Investigators using a variety of preferred terms ranging from ‘blood glucose increased’ and ‘glucose intolerance’ to ‘type 2 diabetes mellitus’. Overall, hyperglycemia-related AEs were reported for 33.6% of subjects in the analysis population. Using laboratory assessment of glycemic status, mean (SD) HbA1c increased to 5.79% (0.81) at Week 13 and remained at or below 5.70 through Week 156 at which time it was 5.72% (0. 98). The HbA1c value exceeded 6.4% at any post-baseline time point in 18 (11.0%) participants. Investigator management of DCCR dose in response to hyperglycemia AEs demonstrated continuation of DCCR in 95.5%, reduction in 27.3%, interruption in 18.2%, and withdrawal in 4.4%. Concomitant medications were initiated in 38.7% of participants. Conclusion: Administration of DCCR for the treatment of hyperphagia in individuals with PWS was generally well tolerated and associated with non-clinically significant increases in mean HbA1c over 3 years of use. Hyperglycemic adverse events were readily monitorable and generally manageable with standard of care concomitant medications allowing for continuation of DCCR therapy. Overall, the safety profile of DCCR in patients with PWS remains favorable.