Clinical trial NCT02034071: Clinical Study of Diazoxide Choline Controlled-Release Tablet (DCCR) in Patients With Prader-Willi Syndrome
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prader-Willi Syndrome
Keywords: Prader-Willi syndrome
Lead sponsor: Essentialis, Inc.
Sponsor class: INDUSTRY
First posted: 2014-01-13
Enrollment: 13
Sex: ALL
Minimum age (years): 10
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Hyperphagia using hyperphagia questionnaire
timeFrame: Change from Day 69 through Day 97
measure: Resting energy expenditure
timeFrame: Change from Day 69 through Day 97
Secondary outcomes:
Other outcomes:
measure: Weight
timeFrame: Percent Change from Baseline through Day 69
measure: Weight
timeFrame: Percent Change from Day 69 through Day 97
measure: Resting energy expenditure
timeFrame: Change from Baseline through Day 69
measure: Hyperphagia using hyperphagia questionnaire
timeFrame: Change from Baseline through Day 69
measure: Percent Body Fat
timeFrame: Change from Baseline through Day 69
measure: Percent Body Fat
timeFrame: Change from Day 69 through Day 97
measure: Lipids
timeFrame: Percent Change from Baseline through Day 69
measure: Lipids
timeFrame: Percent Change from Day 69 Through Day 97
Locations:
city: Orange
country: United States
facility: University of California, Irvine
state: California
Study officials:
affiliation: University of California, Irvine
name: Virginia Kimonis, MD
role: PRINCIPAL_INVESTIGATOR
References: