Clinical Study of Diazoxide Choline Controlled-Release Tablet (DCCR) in Patients With Prader-Willi Syndrome

A Dose Titration Study of Diazoxide Choline Controlled-Release Tablet (DCCR) in Patients With Prader-Willi Syndrome With a Double-Blind, Placebo-Controlled, Randomized Withdrawal Extension

• This is a single-center, open-label, single-arm study with a double-blind, placebo-controlled, randomized withdrawal extension. Patients are initiated on a DCCR dose of about 1.5 mg/kg (maximum starting dose of 145 mg) and are titrated every 14 days to about 2.4 mg/kg, 3.3 mg/kg, 4.2 mg/kg, and 5.1 mg/kg (maximum dose of 507.5 mg). These DCCR doses are equivalent to diazoxide doses of 1.03, 1.66, 2.28, 2.9, and 3.52 mg/kg. The administered dose will be as close to the mg/kg dosing as can be achieved by the available dose strengths of DCCR. Patients will be up-titrated at each visit at the discretion of the investigator. All patients will be continued in the double-blind, placebo-controlled, randomized withdrawal extension. Any patient who showed an increase in resting energy expenditure and/or a reduction in hyperphagia from Baseline through Day 55 or Day 69 will be designated a responder, whereas all others will be designated non-responders. Responders will be randomized in a 1:1 ratio either to continue on active treatment at the dose they were treated with on Day 69 or to the placebo equivalent of that dose for an additional 4 weeks. Non-responders will continue open label treatment during the extension.

Study Overview

• Status: Completed
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: DCCR

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92686
      • University of California, Irvine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 22 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children. adolescents and young adults with genetically confirmed Prader-Willi syndrome
• Ages at ≥ 10 years and ≤ 22 years
• Generally healthy as documented by the medical history, physical examination, vital sign assessments, 12-lead electrocardiogram (ECG), and clinical laboratory assessments
• BMI exceeds the 95th percentile of the age specific BMI value on the CDC BMI charts
• Fasting glucose ≤ 126 mg/dL
• HbA1c ≤ 6.5 %

Exclusion Criteria:

• Administration of investigational drugs within 1 month prior to Screening Visit
• Anticipated requirement for use of prohibited medications
• History of allergic reaction or significant intolerance to: diazoxide, thiazides or sulfonamides
• Anticipate transitions in their care from family home to group home or other similar potentially disruptive changes
• Congestive heart failure or known compromised cardiac reserve
• Any other clinically significant endocrine, cardiovascular, pulmonary, neurological, psychiatric, hepatic, gastrointestinal, hematological, renal, or dermatological disease interfering with the assessments of the investigational drug, according to the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DCCR Open Label - DCCR Double Blind; Patients are initiated on a DCCR dose of about 1.5 mg/kg (maximum starting dose of 145 mg) and are titrated every 14 days through 4 dose levels of DCCR. Patients will be up-titrated at each visit at the discretion of the investigator. Randomized to continue DCCR, at the same dose as they received on Day 69, in the Double-Blind, Placebo-Controlled, Randomized Withdrawal Extension	Drug: DCCR; Other Names: Diazoxide Choline Controlled-Release Tablet
Experimental: DCCR Open Label - Placebo Double Blind; Patients are initiated on a DCCR dose of about 1.5 mg/kg (maximum starting dose of 145 mg) and are titrated every 14 days through 4 dose levels of DCCR. Patients will be up-titrated at each visit at the discretion of the investigator. Randomized to receive placebo equivalent to the DCCR dose received on Day 69 in the Double-Blind, Placebo-Controlled, Randomized Withdrawal Extension	Drug: Placebo; Drug: DCCR; Other Names: Diazoxide Choline Controlled-Release Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hyperphagia using hyperphagia questionnaire	Change from Day 69 through Day 97
Resting energy expenditure	Change from Day 69 through Day 97

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight		Percent Change from Baseline through Day 69
Weight		Percent Change from Day 69 through Day 97
Resting energy expenditure		Change from Baseline through Day 69
Hyperphagia using hyperphagia questionnaire		Change from Baseline through Day 69
Percent Body Fat		Change from Baseline through Day 69
Percent Body Fat		Change from Day 69 through Day 97
Lipids	Percent change from Baseline through Day 69 for triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol	Percent Change from Baseline through Day 69
Lipids	Percent change from Day 69 through Day 97 for triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol	Percent Change from Day 69 Through Day 97

Collaborators and Investigators

• Sponsor: Essentialis, Inc.
• Investigators: Principal Investigator: Virginia Kimonis, MD, University of California, Irvine

Publications and helpful links

Helpful Links

• Prader-Willi Syndrome Association USA
• Genetics Home Reference - Prader-Willi syndrome
• Foundation for Prader-Willi Research - About Prader-Willi syndrome

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: January 8, 2014
• First Submitted That Met QC Criteria: January 9, 2014
• First Posted (Estimate): January 13, 2014

Study Record Updates

• Last Update Posted (Estimate): September 1, 2016
• Last Update Submitted That Met QC Criteria: August 30, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Prader-Willi syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Nootropic Agents; Lipotropic Agents; Diazoxide; Choline
• Other Study ID Numbers: PC025

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No