A Study to Assess RAD011 (Cannabidiol Oral Solution) for the Treatment of Participants With Prader-Willi Syndrome

Study Overview
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Brief Summary
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This was a study investigating RAD011 in participants diagnosed with Prader-Willi Syndrome (PWS). The primary objective of the Phase 2 part of this study was to assess the safety and tolerability of multiple dose levels of RAD011 in order to select 1 or 2 dose level(s) for further evaluation in the Phase 3 part of the study. In Phase 3, the primary objective was to assess the effect of RAD011 on hyperphagia-related behavior in participants with PWS.

Official Title
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A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study of RAD011 (Cannabidiol Oral Solution) for the Treatment of Patients With Prader- Willi Syndrome

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Drug: RAD011
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 8 and 65 years of age (inclusive) at Screening. Genetically confirmed diagnosis of PWS. Documentation of genetically confirmed diagnosis of PWS is acceptable. The same caregiver is available to complete the questionnaire throughout the duration of the study. After completion of the Tolerability period, participants will have a mean Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score ≥13 and a decrease of HQ-CT score no more than 7 during Tolerability (run-in) period. If receiving growth hormone, psychotropic therapy, metabolic treatments that could affect appetite (including metformin), and other treatment including thyroid hormone, must be on the same medication and dose for at least 90 days prior to consent/assent Exclusion Criteria: Known use of cannabis or cannabinoid containing products (including topical products) within 90 days prior to consent/ assent. Use of prescription or over-the-counter weight loss agents within 90 days prior to consent/assent. Implementation of new food or environmental restrictions within 90 days of consent/ assent. If living in a group home, participant spends less than 25 waking hours with their caregiver per week. Uncontrolled chronic conditions (diabetes, sleep apnea, etc.) as determined by the Investigator.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: RAD011 40 milligrams per kilogram (mg/kg)<br>Participants were administered 40 mg/kg of RAD011 orally daily with food. | Drug: RAD011<br>* Cannabidiol Oral Solution (containing synthetic cannabidiol)<br>|
| Active Comparator: RAD011 20 mg/kg<br>Participants were administered 20 mg/kg of RAD011 orally daily with food. | Drug: RAD011<br>* Cannabidiol Oral Solution (containing synthetic cannabidiol)<br>|
| Active Comparator: RAD011 10 mg/kg<br>Participants were administered 10 mg/kg of RAD011 orally daily with food. | Drug: RAD011<br>* Cannabidiol Oral Solution (containing synthetic cannabidiol)<br>|
| Placebo Comparator: Placebo<br>Participants were administered a placebo matching to RAD011, orally daily with food. | Drug: Placebo<br>* Matching Placebo for RAD011<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 34 in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Questionnaire | The HQ-CT measures hyperphagia by Prader-Willi syndrome (PWS)-specialized clinicians. The HQ-CT generates a score ranging from 0 to 36, where a higher score represents more severe abnormal food related behaviors. The change from baseline was calculated from two time points as the value at the later time point minus the value at the earlier time point. | Baseline, Week 34 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 34 in Prader-Willi Syndrome (PWS)- Associated Irritability Using the Aberrant Behavior Checklist (ABC) Questionnaire - Irritability Subscale (ABC-I) | The ABC questionnaire is an informant-rated questionnaire assessing severity of behavioral symptoms. The Irritability subscale of the ABC covers symptoms such as agitation, aggression, meltdowns, and self-harm. The ABC-I contains 15 items and each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score is the sum of individual items scores which ranges from 0 (no problem) to 45 (severe problem), with higher score indicating more severe condition. | Baseline, Week 34 | 
| Change From Baseline to Week 34 in Hyperphagia as Measured by the Clinician Global Impression of Change (CGI-C) | The CGI-C of hyperphagia is a single-item, clinician-rated measure, assessing the clinician's impression about changes in the patient's hyperphagia condition since the start of taking the study medication at the initiation of the Tolerability Period. The CGI-C of hyperphagia utilizes a 5-point response scale: 1=Much better; 2=A little better; 3=No change; 4=A little worse; 5=Much worse. Higher scores mean a worse outcome. | Baseline, Week 34 | 
| Change From Baseline to Week 34 in Hyperphagia as Measured by the Clinician Global Impression of Severity (CGI-S) | The CGI-S of hyperphagia is a single-item, clinician-rated measure, assessing the clinician's impression of the severity of a patient's hyperphagia condition. The CGI-S of hyperphagia utilizes a 5-point response scale: 1=None; 2=Mild; 3=Moderate; 4=Severe; 5=Very Severe. Higher scores mean a worse outcome. | Baseline, Week 34 |