Clinical trial NCT03274856: A Study of GLWL-01 in Patients With Prader-Willi Syndrome
Official title: A Phase 2 Study to Evaluate Efficacy, Safety, and Pharmacokinetics of GLWL-01 in the Treatment of Patients With Prader-Willi Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prader-Willi Syndrome
Lead sponsor: GLWL Research Inc.
Sponsor class: OTHER
First posted: 2017-09-07
Enrollment: 19
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT)
timeFrame: Up to approximately 4 weeks of double-blind treatment
Secondary outcomes:
measure: Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs
timeFrame: Baseline up to approximately 18 weeks
measure: Caregiver Global Impression of Change (CGIC)
timeFrame: Up to approximately 4 weeks of double-blind treatment
measure: Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12)
timeFrame: Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose
measure: Maximum Observed Drug Concentration (Cmax)
timeFrame: Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Cleveland
country: United States
facility: University Hospitals, Cleveland Medical Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Edmonton
country: Canada
facility: Alberta Diabetes Institute, University of Alberta
state: Alberta
city: Montreal
country: Canada
facility: CRCHUM
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier Universitaire Ste-Justine
state: Quebec
Study officials:
affiliation: GLWL Research Inc.
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.