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

Phase 2

Completed

• Conditions: Prader-Willi Syndrome
• Interventions: Drug: GLWL-01; Drug: Placebo

• Registration Number: NCT03274856
• Lead Sponsor: GLWL Research Inc.

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2017-09-05
• Study First Submitted QC: 2017-09-05
• Study First Posted: 2017-09-07
• Study Start: 2018-02-20
• Primary Completion: 2019-06-12
• Study Completion: 2019-06-12
• Status Verified: 2020-03
• Results First Submitted: 2020-03-09
• Results First Submitted QC: 2020-03-09
• Last Update Submitted: 2020-03-09
• Results First Posted: 2020-03-27
• Last Update Posted: 2020-03-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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:

  1. 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
  2. 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
  3. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence 1	Placebo	GLWL-01 (450mg) twice a day/ Placebo
Treatment Sequence 2	GLWL-01	Placebo / GLWL-01 (450mg), twice a day
Treatment Sequence 2	Placebo	Placebo / GLWL-01 (450mg), twice a day
Treatment Sequence 1	GLWL-01	GLWL-01 (450mg) twice a day/ Placebo

Primary Outcome Measures

Name	Time	Method
Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT)	Up to approximately 4 weeks of double-blind treatment	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.

Secondary Outcome Measures

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

Trial Locations

Locations (7)

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States

CRCHUM; 🇨🇦 Montreal, Quebec, Canada

Alberta Diabetes Institute, University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

University Hospitals, Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

Centre Hospitalier Universitaire Ste-Justine; 🇨🇦 Montreal, Quebec, Canada

University of Florida; 🇺🇸 Gainesville, Florida, United States

Rady Children's Hospital San Diego; 🇺🇸 San Diego, California, United States