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

• ClinicalTrials.gov Identifier: NCT02034071
• Recruitment Status: Completed
• First Posted: January 13, 2014
• Last Update Posted: September 1, 2016
• Sponsor: Essentialis, Inc.
• Information provided by (Responsible Party): Essentialis, Inc.

Study Description

Brief Summary:

• 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.

Condition or disease	Intervention/treatment	Phase
Prader-Willi Syndrome	Drug: DCCR; Drug: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2014
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

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 Name: 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: DCCR; Other Name: Diazoxide Choline Controlled-Release Tablet; Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Hyperphagia using hyperphagia questionnaire [ Time Frame: Change from Day 69 through Day 97 ]
2. Resting energy expenditure [ Time Frame: Change from Day 69 through Day 97 ]

Other Outcome Measures:

1. Weight [ Time Frame: Percent Change from Baseline through Day 69 ]
2. Weight [ Time Frame: Percent Change from Day 69 through Day 97 ]
3. Resting energy expenditure [ Time Frame: Change from Baseline through Day 69 ]
4. Hyperphagia using hyperphagia questionnaire [ Time Frame: Change from Baseline through Day 69 ]
5. Percent Body Fat [ Time Frame: Change from Baseline through Day 69 ]
6. Percent Body Fat [ Time Frame: Change from Day 69 through Day 97 ]
7. Lipids [ Time Frame: Percent Change from Baseline through Day 69 ]
   Percent change from Baseline through Day 69 for triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol
8. Lipids [ Time Frame: Percent Change from Day 69 Through Day 97 ]
   Percent change from Day 69 through Day 97 for triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

University of California, Irvine

Orange, California, United States, 92686

Sponsors and Collaborators

Essentialis, Inc.

Investigators

• Principal Investigator: Virginia Kimonis, MD; University of California, Irvine

More Information

Additional Information:

Prader-Willi Syndrome Association USA 

Genetics Home Reference - Prader-Willi syndrome 

Foundation for Prader-Willi Research - About Prader-Willi syndrome 

• Responsible Party: Essentialis, Inc.
• ClinicalTrials.gov Identifier: NCT02034071
• Other Study ID Numbers: PC025
• First Posted: January 13, 2014
• Last Update Posted: September 1, 2016
• Last Verified: August 2016

Keywords provided by Essentialis, Inc.:

Prader-Willi syndrome

Additional relevant MeSH terms:

Prader-Willi Syndrome; Syndrome; Disease; Pathologic Processes; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Obesity; Overnutrition; Nutrition Disorders; Diazoxide; Choline; Lipotropic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Lipid Regulating Agents; Nootropic Agents; Antihypertensive Agents; Vasodilator Agents