Cannabidiol Oral Solution for the Treatment of Patients With Prader-Willi Syndrome

Study Overview
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Brief Summary
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The primary objective of this study is to assess the efficacy of cannabidiol oral solution on hyperphagia-related behavior in patients with Prader-Willi Syndrome (PWS). The secondary objectives of this study are to assess the efficacy, safety and tolerability, impact on quality of life, and impact on physical activity of cannabidiol oral solution in patients with PWS.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Efficacy, Safety, and Tolerability of 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: Cannabidiol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant and/or parent(s)/caregiver(s) fully comprehend the informed consent form and assent form, understand all study procedures, and can communicate satisfactorily with the investigator and study coordinator, in accordance with applicable laws, regulations, and local requirements. Participants with a genetically confirmed diagnosis of Prader-Willi Syndrome using standard deoxyribonucleic acid methylation test or fluorescent in situ hybridization. Documentation of genetically confirmed diagnosis of Prader-Willi Syndrome is acceptable. A score of ≥10 on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). A caregiver is available to complete the HQ-CT. If female, is either not of childbearing potential (defined as premenarchal or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or practicing one of the following medically acceptable methods of birth control: Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives for a minimum of 1 full cycle (based on the participant's usual menstrual cycle period) before study drug administration. Total abstinence from sexual intercourse since the last menses before study drug administration. Intrauterine device. Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream). Adequate renal function, defined as serum creatinine ≤ 1.5*upper limit of normal (ULN) and urine protein/creatinine ratio ≤0.4. The Investigator may deem the participant eligible if he or she judges the laboratory values to be not clinically significant. Adequate hepatic function, defined as total bilirubin ≤ 1.5*ULN and aspartate aminotransferase and alanine aminotransferase levels ≤ 3*ULN. Growth hormone treatment will be permitted if doses have been stable for at least 1 month prior to screening. Psychotropic treatment will be permitted and should be stable at least 6 weeks prior to screening. Any other treatment including thyroid hormones should be stable for at least 6 weeks prior to screening. Exclusion Criteria: Known use of cannabis or cannabinoid-containing products for 4 weeks prior to baseline. History of chronic liver diseases, such as cirrhosis or chronic hepatitis due to any cause, or suspected alcohol abuse. Use of weight loss agents or drugs known to affect appetite (including glucagon-like peptide-1 [GLP-1] analogs) within 2 months prior to screening. Uncontrolled Type I and Type II diabetes. Currently taking concomitant medication that are strong-moderate inhibitors/inducers/sensitive substrates with a narrow therapeutic index for CYP2C19 or CYP3A. Co-morbid condition or disease (such as respiratory disease, heart disease, or psychiatric disorder) diagnosed less than 1 month prior to screening. History or presence of gastrointestinal or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs as determined by the Investigator. Participants who have participated in any other trials involving an investigational product or device within 30 days of screening or longer as required by local regulations. Clinically significant abnormalities on electrocardiogram at screening or other evidence of heart disease as determined by the Investigator. Has screening systolic blood pressure ≥160 millimeters of mercury (mmHg) and diastolic blood pressure >100 mm Hg (may be repeated 1 additional time after 5 minutes rest to verify). Participants with hypertensive levels lower than those specified may be excluded at the Investigator's discretion if deemed to be in the best interest of the participant. Currently taking felbamate. Uncontrolled sleep apnea. Pregnant or lactating female. History of hypersensitivity to drugs with a similar chemical structure or class as cannabidiol. Unwillingness or inability to follow the procedures outlined in the protocol. Participant judged by the investigator or sponsor (or designee) as unable to comply with the treatment protocol, including appropriate supportive care, follow-up and research tests. Positive drug screen, including tetrahydrocannabinol, at time of screening. Creatinine clearance test of < 30 milliliters/minute (mL/min).

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol<br>Cannabidiol oral solution (40 milligram/kilogram/day [40 mg/kg/day]) divided into two daily doses with a standard meal | Drug: Cannabidiol<br>* Oral solution<br>|
| Placebo Comparator: Placebo<br>Matching placebo solution divided into two daily doses with a standard meal | Drug: Placebo<br>* Matching oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hyperphagia Behavior as Measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) | 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: value at Week 13 minus value at Baseline. | Baseline, Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline In Total Body Weight | Total body weight refers to participants' weight throughout the study. 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: value at Week 13 minus value at Baseline. | Baseline, Week 13 | 
| Responder Rate From Baseline Through Study Completion | A responder was defined as having a 6 or more points decrease in HQ-CT score. | Baseline up to Week 13 | 
| Change In Patient Global Impression Of Change (PGI-C) Questionnaire | The change in PGI-C scores at Week 3, Week 9, and Week 13 of the participant are evaluated. | Week 3, Week 13 | 
| Change From Baseline In The Three Factor Eating Questionnaire - 18-item Version (TFEQ-R18) | The change from baseline to Week 13 of the participant's TFEQ-R18 score is evaluated. | Baseline, Week 13 | 
| Change From Baseline In Quality Of Life [Patient-Reported Outcomes Measurement Information System (PROMIS) Life Satisfaction And Positive Affect Questionnaires] | The change from baseline to Week 13 of the participant's quality of life (PROMIS life satisfaction and positive affect questionnaire) score is evaluated. | Baseline, Week 13 | 
| Change From Baseline In Physical Activity (PROMIS Physical Activity And Fatigue Questionnaires) | The change from baseline to Week 13 of the participant's physical activity (PROMIS physical activity and fatigue questionnaires) score is evaluated. | Baseline, Week 13 |