A Study of GLWL-01 in Patients With Prader-Willi Syndrome

Study Overview
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Brief Summary
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The aim of this study is to evaluate efficacy, safety, and pharmacokinetics of GLWL-01 in the treatment of patients with Prader-Willi Syndrome (PWS).

Detailed Description
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Participants will be assigned to one of two treatment sequences (GLWL-01/Placebo or Placebo/GLWL-01), with each sequence consisting of two treatment periods separated by a washout period

Official Title
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A Phase 2 Study to Evaluate Efficacy, Safety, and Pharmacokinetics of GLWL-01 in the Treatment of Patients With Prader-Willi Syndrome

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Drug: GLWL-01
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of PWS based on genetic confirmation using DNA method Body mass index (BMI) of 27 to 60 kg/m2 No evidence of weight excursion beyond 10% of baseline weight Patients must provide assent and have a reliable caregiver (must have been caring for the patient for at least 6 months) who provides a separate written informed consent to participate. The caregiver is expected to be the primary caregiver throughout the study and must be in frequent contact with the patient (defined as at least 4 awake hours per day). The caregiver must be able to communicate with site personnel and in the investigator's opinion must have adequate literacy to complete questionnaires. If a caregiver cannot continue, 1 caregiver replacement is allowed Are on a stable diet and exercise regimen for >2 months prior Exclusion Criteria: Current enrollment in or discontinuation within the last 30 days from a clinical trial involving any investigational drug or device Are currently living in a group home for more than 50% of the time A history or presence of other medical illness that indicates a medical problem that would preclude study participation Have an estimated glomerular filtration rate <60 mL/minute/1.73 m2. Have macroalbuminuria (defined as spot urine albumin to creatinine ratio of >300 μg/mg) or hematuria Are hypertensive (defined as sitting systolic blood pressure (BP) greater than or equal to (≥)140 millimeters of mercury (mmHg) and diastolic BP ≥90 mmHg) Patients on weight loss medications within 30 days of dosing, or with a history of bariatric surgery Unable to refrain from or anticipates the use of: Any drugs known to be significant inhibitors of Cytochrome P450, family 3, subfamily A (CYP)3A enzymes and/or P-glycoprotein (P-gp) including regular consumption of grapefruit or grapefruit juice for 14 days prior to the first dose. Acetaminophen (up to 2 grams per 24-hour period) may be permitted Any drugs known to be significant inducers of Cytochrome P450, family 3, subfamily A (CYP3A) enzymes and/or P-gp, including St. John's Wort Any medications that prolong the QT/QTc interval, unless the participant has been stable on the medication for at least 3 months and has a corrected QT interval (QTc) <450 msec Currently taking simvastatin >10 mg per day, atorvastatin >20 mg per day, or lovastatin >20 mg per day, or have a history of statin-induced myopathy/rhabdomyolysis Unsuitable for inclusion in the study in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 16 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment Sequence 1<br>GLWL-01 (450mg) twice a day/ Placebo | Drug: GLWL-01<br>* Oral administration of 3 capsules, twice a day<br>Drug: Placebo<br>* Oral administration of 3 capsules, twice a day<br>|
| Other: Treatment Sequence 2<br>Placebo / GLWL-01 (450mg), twice a day | Drug: GLWL-01<br>* Oral administration of 3 capsules, twice a day<br>Drug: Placebo<br>* Oral administration of 3 capsules, twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) | GLWL-01 compared with placebo on the post-treatment HQ-CT score. Total range of score of zero to 36, with higher score indicating a worse outcome. | Up to approximately 4 weeks of double-blind treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs | Evaluate the safety and tolerability of GLWL-01 | Baseline up to approximately 18 weeks | 
| Caregiver Global Impression of Change (CGIC) | GLWL-01 compared with placebo in the CGIC. Score ranges from 1 to 7, with larger number indicating a worse outcome. | Up to approximately 4 weeks of double-blind treatment | 
| Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12) | Pharmacokinetics (PK) after single and multiple oral dosing | Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose | 
| Maximum Observed Drug Concentration (Cmax) | Pharmacokinetics after single and multiple oral dosing | Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose |