Clinical Study PC025
Essentialis recently completed clinical study PC025. It 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 28 days. Across both phases of the study, subjects were treated for a total of 98 days, or more than 3 months. The study was conducted at a single site, the University of California, Irvine under the direction of Dr. Virginia Kimonis, a PWS expert.
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
There was a highly significant and clinically relevant effect of DCCR treatment on hyperphagia (-32%, p=0.003) at the end of open label treatment. The effect on hyperphagia persisted for more than 3 months 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, and more than 90% of subjects showed improvements in hyperphagia.
Body composition, using DEXA, was measured at the beginning and end of open label treatment. Ten weeks of treatment with DCCR resulted in the following highly significant and clinically relevant changes in body composition: body fat mass (-3.8%, p=0.011, 75% responded with improvement), lean body mass (+5.4%, p=0.001, 90% responded with improvement), and lean body mass/fat mass ratio (+9.8%, p=0.002, 100% responded with improvement). 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 (-22%, p=0.007).
Treatment with DCCR for 10 weeks 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 20% at 10 weeks (p=0.0006 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. Three months of treatment with DCCR, through both the open label and double blind phases of clinical study PC025, resulted in a 42% reduction in triglycerides, an 11% reduction in total cholesterol, a 25% increase in HDL cholesterol and a 13% reduction in non-HDL cholesterol.
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.
Other Clinical Studies
Essentialis has completed 7 other clinical trials with DCCR which randomized more nearly 280 patients, 200 of whom were treated with DCCR.