Open-Label Extension Study of DCCR in PWS Followed by Double-Blind, Placebo-Controlled, Randomized Withdrawal Period

Study Overview
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Brief Summary
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This is a multi-center, multi-period study with an open-label period followed by a double-blind, placebo-controlled, randomized withdrawal period evaluating the safety and efficacy of DCCR treatment.

Detailed Description
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115 PWS participants who completed clinical study C601 will be enrolled into the OLE Period. All participants in the Open Label Extension (OLE) Period will receive open-label DCCR. The actual number of participants eligible to enroll in the double-blind, placebo-controlled, randomized withdrawal (RW) period will be limited to those participants taking DCCR in the OLE Period at the time of the RW Period Visit 1 (Baseline/Randomization Visit).The treatment groups in the C602 RW Period are those participants randomized to receive DCCR and those participants randomized to receive Placebo. Participants will be randomized in a 1:1 ratio (DCCR:Placebo).

Official Title
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An Open-Label, Long-Term Safety and Efficacy Evaluation of Diazoxide Choline Extended-Release Tablets in Participants With Prader-Willi Syndrome With a Double-Blind, Placebo-Controlled, Randomized Withdrawal Period

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Drug: DCCR
* Drug: DCCR
* Drug: Placebo for DCCR


Participation Criteria
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Eligibility Criteria
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OLE Period Key Inclusion Criteria: Successful completion of clinical study C601 Provide voluntary, written informed consent (parent(s) / legal guardian(s) of patient); provide voluntary, written assent (subjects, as appropriate) OLE Period Key Exclusion Criteria: Positive urine pregnancy test (in females of child-bearing potential) or females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 90 days after study participation Any new disease, condition, or circumstance which would prevent, in the opinion of the Investigator, the patient from completing all study visits and assessments required by the protocol (e.g., an anticipated change of care setting) RW Period Key Inclusion Criteria: Provide voluntary, written informed consent (parent[s] / legal guardian[s] of participant); provide voluntary, written assent (participants, as appropriate); this includes consent for randomization and potential treatment with placebo for up to 16 weeks Currently participating in clinical study C602 and complete the OLE End of Treatment Visit procedures RW Period Key Exclusion Criteria: Positive urine pregnancy test (in females of child-bearing potential) Females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 30 days after study participation

Ages Eligible for Study
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Minimum Age: 4 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: OLE DCCR<br>75 - 525 mg DCCR | Drug: DCCR<br>* Once daily oral administration of open-label DCCR tablet(s) during the OLE Period<br>|
| Experimental: RW DCCR<br>75 - 525 mg DCCR | Drug: DCCR<br>* Once daily oral administration of double-blind (DCCR) tablet(s) during the RW Period<br>|
| Placebo Comparator: RW Placebo<br>75 - 525 mg Placebo for DCCR | Drug: Placebo for DCCR<br>* Once daily oral administration of double-blind (placebo for DCCR) tablet(s) during the RW Period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety of DCCR by evaluating the incidence and severity of adverse events reported | Safety analyses will be conducted in all participants who receive at least one dose of DCCR. Adverse events will be described by type and level of severity. | Baseline to end of OLE (up to 4 years) | 
| Change from RW Period Baseline in HQ-CT Total Score | Hyperphagia-related behaviors will be assessed by the hyperphagia questionnaire for clinical trials (HQ-CT), an instrument designed to measure symptoms of food related preoccupations and behaviors. The HQ-CT consists of nine items with responses ranging from 0-4 (best to worst). Scores from 9 items will be summed for a possible total score range of 0-36. | RW Period Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in HQ-CT Total Score | Hyperphagia-related behaviors will be assessed by the hyperphagia questionnaire for clinical trials (HQ-CT), an instrument designed to measure symptoms of food related preoccupations and behaviors. The HQ-CT consists of nine items with responses ranging from 0-4 (best to worst). Scores from 9 items will be summed for a possible total score range of 0-36. | Baseline to end of OLE (up to 4 years) | 
| Change in Body Fat Mass | Change in Body Fat Mass (kg) using DXA | Baseline to end of OLE (up to 4 years) | 
| Clinical Global Impression of Improvement (CGI-I) | CGI-I is a single statement designed to assess the Investigator's overall perception of change in the subject's condition across the course of the clinical trial. The Investigator provides a response to Compared to the subject's condition at enrollment, the subject's condition is: by rating the subject's behavior using a 7-point response scale (best to worst). | RW Period Week 16 | 
| Clinical Global Impression of Severity (CGI-S) | The CGI-S is a single statement designed to assess the Investigator's overall perception of the severity of the participant's illness across the course of the clinical trial. The Investigator provides a response to Considering your total clinical experience with this particular population, how ill is this participant at this time: by rating the subject's behavior using a 7-point response scale (best to worst). | RW Period Week 16 | 
| Assess the safety of DCCR by evaluating the incidence and severity of adverse events reported | Safety analyses will be conducted in all participants who receive at least one dose of randomized withdrawal study drug. Adverse events will be described by type and level of severity. | through the end of the RW Period, 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PWS, Prader-Willi Syndrome