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

• ClinicalTrials.gov Identifier: NCT03274856
• Recruitment Status: Completed
• First Posted: September 7, 2017
• Results First Posted: March 27, 2020
• Last Update Posted: March 27, 2020
• Sponsor: GLWL Research Inc.
• Information provided by (Responsible Party): GLWL Research Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Prader-Willi Syndrome	Drug: GLWL-01; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study to Evaluate Efficacy, Safety, and Pharmacokinetics of GLWL-01 in the Treatment of Patients With Prader-Willi Syndrome
• Actual Study Start Date: February 20, 2018
• Actual Primary Completion Date: June 12, 2019
• Actual Study Completion Date: June 12, 2019

Arms and Interventions

Arm	Intervention/treatment
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
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

Outcome Measures

Primary Outcome Measures :

1. Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) [ Time Frame: 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 :

1. Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs [ Time Frame: Baseline up to approximately 18 weeks ]
   Evaluate the safety and tolerability of GLWL-01
2. Caregiver Global Impression of Change (CGIC) [ Time Frame: 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.
3. Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12) [ Time Frame: 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
4. Maximum Observed Drug Concentration (Cmax) [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Rady Children's Hospital San Diego

San Diego, California, United States, 92123

United States, Florida

University of Florida

Gainesville, Florida, United States, 32601

United States, Ohio

University Hospitals, Cleveland Medical Center

Cleveland, Ohio, United States, 44106

United States, Tennessee

Vanderbilt University

Nashville, Tennessee, United States, 37232

Canada, Alberta

Alberta Diabetes Institute, University of Alberta

Edmonton, Alberta, Canada, T6G 2B7

Canada, Quebec

CRCHUM

Montreal, Quebec, Canada, H2W 1T8

Centre Hospitalier Universitaire Ste-Justine

Montreal, Quebec, Canada, H3T 1C5

Sponsors and Collaborators

GLWL Research Inc.

Investigators

• Study Director: Study Director; GLWL Research Inc.

  Study Documents (Full-Text)

Documents provided by GLWL Research Inc.:

Study Protocol  [PDF] June 27, 2018

Statistical Analysis Plan  [PDF] March 19, 2019

More Information

• Responsible Party: GLWL Research Inc.
• ClinicalTrials.gov Identifier: NCT03274856
• Other Study ID Numbers: GLWL-PWS
• First Posted: September 7, 2017
• Results First Posted: March 27, 2020
• Last Update Posted: March 27, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Prader-Willi Syndrome; Syndrome; Disease; Pathologic Processes; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Obesity; Overnutrition; Nutrition Disorders