In 2015 FPWR co-funded a phase 2 study to investigate diazoxide choline controlled-release in patients with PWS. Results from the study were recently published in PLoS ONE and are summarized below.
The phase 2 study included a 10-week Open-Label Treatment Period during which time subjects were dose escalated, followed by a 4-week Double-Blind, Placebo Controlled Treatment Period.
13 overweight or obese, adolescent and adult subjects with genetically-confirmed PWS with an average age of 15.5±2.9 years were enrolled in the study. There was a statistically significant reduction in hyperphagia at the end of the Open-Label Treatment Period (-4.32, n = 11, p = 0.006). The onset of effect on hyperphagia was rapid and greater reductions in hyperphagia were seen in subjects with moderate to severe Baseline hyperphagia (-5.50, n = 6, p = 0.03), in subjects treated with the highest dose (-6.25, n = 4, p = 0.08), and in subjects with moderate to severe Baseline hyperphagia treated with the highest dose (-7.83, n = 3, p = 0.09).
DCCR treatment resulted in:
- a reduction in the number of subjects displaying aggressive behaviors (-57.1%, n = 10, p = 0.01)
- clinically relevant reductions in fat mass (-1.58 kg, n = 11, p = 0.02), and
- increases in lean body mass (2.26 kg, n = 11, p = 0.003).
There was a corresponding decrease in waist circumference, and trends for improvements in lipids and insulin resistance. The most common adverse events were peripheral edema and transient increases in glucose. Many of the adverse events were common medical complications of PWS and diazoxide.
A phase 3 study of DCCR is now underway and enrolling people with PWS ages 4 and up.