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

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

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).

Study Overview

• Status: Completed
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: GLWL-01; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Alberta Diabetes Institute, University of Alberta
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Centre Hospitalier Universitaire Ste-Justine
    • Montreal, Quebec, Canada, H2W 1T8
      • CRCHUM
• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego
  • Florida
    • Gainesville, Florida, United States, 32601
      • University of Florida
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals, Cleveland Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Treatment Sequence 1; GLWL-01 (450mg) twice a day/ Placebo	Drug: GLWL-01; Oral administration of 3 capsules, twice a day; Drug: Placebo; Oral administration of 3 capsules, twice a day
OTHER: Treatment Sequence 2; Placebo / GLWL-01 (450mg), twice a day	Drug: GLWL-01; Oral administration of 3 capsules, twice a day; Drug: Placebo; Oral administration of 3 capsules, twice a day

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GLWL Research Inc.
• Investigators: Study Director: Study Director, GLWL Research Inc.

Publications and helpful links

General Publications

• Miller JL, Lacroix A, Bird LM, Shoemaker AH, Haqq A, Deal CL, Clark KA, Ames MH, Suico JG, de la Pena A, Fortier C. The Efficacy, Safety, and Pharmacology of a Ghrelin O-Acyltransferase Inhibitor for the Treatment of Prader-Willi Syndrome. J Clin Endocrinol Metab. 2022 May 17;107(6):e2373-e2380. doi: 10.1210/clinem/dgac105.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 20, 2018
• Primary Completion (ACTUAL): June 12, 2019
• Study Completion (ACTUAL): June 12, 2019

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 5, 2017
• First Posted (ACTUAL): September 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 9, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome
• Other Study ID Numbers: GLWL-PWS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes