Prader-Willi Syndrome
Conditions
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
Interventions
DRUGGLWL-01
Oral administration of 3 capsules, twice a day
DRUGPlacebo
Oral administration of 3 capsules, twice a day
Sponsors
GLWL Research Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada, United States
Participant flow
Recruitment details
Five additional participants screened but not randomized
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence 1 GLWL-01 (450mg) twice a day/ Placebo. Participants randomized to 1 of 2 treatment sequences; GLWL-01/placebo or placebo/GLWL-01 (Treatment Period 1 double-blind treatment phase/Treatment Period 2 double-blind treatment phase). During single-blind placebo lead-in phases, participants receive 3 capsules of 150-mg placebo twice daily (BID) for 14 days. During double-blind treatment phases, participants receive 3 capsules of 150-mg GLWL-01 (450 mg total dose) BID or identical placebo BID for 28 days | 10 |
| Treatment Sequence 2 Placebo / GLWL-01 (450mg), twice a day. Participants randomized to 1 of 2 treatment sequences; GLWL-01/placebo or placebo/GLWL-01 (Treatment Period 1 double-blind treatment phase/Treatment Period 2 double-blind treatment phase). During single-blind placebo lead-in phases, participants receive 3 capsules of 150-mg placebo twice daily (BID) for 14 days. During double-blind treatment phases, participants receive 3 capsules of 150-mg GLWL-01 (450 mg total dose) BID or identical placebo BID for 28 days | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | Treatment Sequence 1 | Total | Treatment Sequence 2 |
|---|---|---|---|
| Age, Continuous | 22.0 years STANDARD_DEVIATION 5.54 | 22.1 years STANDARD_DEVIATION 5.07 | 22.1 years STANDARD_DEVIATION 4.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 17 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 19 Participants | 9 Participants |
| Region of Enrollment Canada | 2 participants | 5 participants | 3 participants |
| Region of Enrollment United States | 8 participants | 14 participants | 6 participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 8 / 19 | 7 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
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.
Time frame: Up to approximately 4 weeks of double-blind treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLWL-01 | Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) | 15.9 score on a scale | Standard Error 1.21 |
| Placebo | Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) | 14.7 score on a scale | Standard Error 1.23 |
Secondary
Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12)
Pharmacokinetics (PK) after single and multiple oral dosing
Time frame: Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose
Population: Because PK data were collected only during Treatment 1, and the patients were randomized 1:1 to GLWL-01 or placebo, PK data were available from 9 patients. Evaluable data only available to compute AUC for some participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GLWL-01 | Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12) | 55608 ng*h/mL | Geometric Coefficient of Variation 23.6 |
| Placebo | Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12) | 121620 ng*h/mL | Geometric Coefficient of Variation 23.7 |
Secondary
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.
Time frame: Up to approximately 4 weeks of double-blind treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLWL-01 | Caregiver Global Impression of Change (CGIC) | 4.0 score on a scale | Standard Error 0.18 |
| Placebo | Caregiver Global Impression of Change (CGIC) | 3.8 score on a scale | Standard Error 0.19 |
Secondary
Maximum Observed Drug Concentration (Cmax)
Pharmacokinetics after single and multiple oral dosing
Time frame: Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GLWL-01 | Maximum Observed Drug Concentration (Cmax) | 7885 ng/mL | Geometric Coefficient of Variation 34.4 |
| Placebo | Maximum Observed Drug Concentration (Cmax) | 13695 ng/mL | Geometric Coefficient of Variation 29.2 |
Secondary
Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs
Evaluate the safety and tolerability of GLWL-01
Time frame: Baseline up to approximately 18 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GLWL-01 | Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs | 8 Participants |
| Placebo | Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs | 7 Participants |