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

Study Overview
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Brief Summary
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• 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.

Official Title
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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

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Drug: DCCR
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DCCR Open Label - DCCR Double Blind<br>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<br> <br> * Other names: Diazoxide Choline Controlled-Release Tablet;|
| Experimental: DCCR Open Label - Placebo Double Blind<br>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<br> <br> * Other names: Diazoxide Choline Controlled-Release Tablet;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prader-Willi syndrome