Clinical Study PC025

Clinical study PC025 was a randomized withdrawal study designed to evaluate the safety and efficacy of DCCR in Prader-Willi syndrome (PWS) patients.  The study enrolled 13 male and female genetically-confirmed PWS subjects between the ages of 10 and 22 years old.  Subjects were titrated through several doses of DCCR over 70 days (10 weeks) of open-label treatment.  If, at the end of the 10 weeks of open-label treatment, subjects responded to DCCR with a reduction in hyperphagia or an increase in resting energy expenditure, they were eligible to participate in the double-blind, placebo-controlled, randomized withdrawal phase of the study.  In that phase, half of the patients were randomized to continue treatment on active drug and half were randomized to receive placebo.  The duration of the randomized withdrawal phase was 4 weeks.  Across both phases of the study, subjects were treated for a total of 98 days, or more than 3 months.  Some of the subjects in the study returned for a 6 month open label extension to the study. The study was conducted at a single site, the University of California, Irvine under the direction of Dr. Virginia Kimonis, a medical geneticist who studies PWS. For further information about the study, please visit the study description at www.clinicaltrials.gov using this link:  http://www.clinicaltrials.gov/ct2/show/NCT02034071.

Hyperphagia in the study was measured using a questionnaire that was posed to the parent or caregiver. It was administered two before the subjects started DCCR treatment and again at each study visit. There was a highly significant effect of DCCR treatment on hyperphagia (-32%, p=0.003) at the end of open label treatment.  The effect on hyperphagia persisted through the end of the study in those who were randomized to continue on DCCR through the double blind phase, but regressed back towards baseline in those randomized to placebo.  The effect of DCCR on hyperphagia was dose dependent.

Twenty three PWS associated behaviors, 6 of which were defined as aggressive, threatening or destructive, were measured at the start of the study and again at the end of 10 weeks of treatment. Treatment with DCCR resulted in a clinically relevant and statistically significant improvement in aggressive, threatening and destructive behavior reducing the frequency of subjects displaying these behaviors from 70% at baseline to 30% at 10 weeks (p=0.006 for the change in frequency).

Treatment with DCCR resulted in improvements in cardiovascular risk factors.  Treated subjects showed significant improvements in circulating triglyceride levels, total cholesterol, LDL cholesterol and non-HDL cholesterol at the end of open label treatment.  PWS subjects treated with DCCR through both the open label and double blind phases of clinical study PC025 showed a 40% reduction in triglycerides, an 11% reduction in total cholesterol, and a 12% reduction in non-HDL cholesterol.

Body composition was measured at the beginning and end of open label treatment using Dual-energy X-ray absorptiometry.  Ten weeks of treatment with DCCR resulted in the following highly significant changes in body composition: body fat mass (-3.8%, p=0.011), lean body mass (+5.4%, p=0.001), and lean body mass/fat mass ratio (+9.8%, p=0.003).  Each of the effects of DCCR on body composition showed strong dose dependence.  Consistent with the reduction in body fat, there was a significant reduction in waist circumference (-3.5 cm, p=0.003) and in leptin (-24%, p=0.0013).

There was also a trend towards improved insulin sensitivity as measured by HOMA-IR (-44%, p=0.095).

DCCR was well tolerated with most adverse events being of mild to moderate severity and improving or resolving as dosing continued. Many of the adverse events were common medical complications of PWS. During the double blind phase, there were similar numbers of subjects who experienced adverse events in the DCCR and placebo arms.

Read More
CLINICAL STUDY (PC025) – Soleno