Prader-Willi Syndrome
Conditions
Keywords
Prader-Willi Syndrome, obesity, hyperphagia
Brief summary
The purpose of this study was to evaluate the effects of a once daily subcutaneous injectable formulation of setmelanotide in obese participants with Prader-Willi syndrome on tolerability, weight loss, and hyperphagia-related behavior. The study drug (setmelanotide and placebo) was administered in a blinded fashion.
Interventions
DRUGSetmelanotide
subcutaneous injection
DRUGPlacebo
Subcutaneous injection
Sponsors
Rhythm Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. PWS due to chromosome 15 micro-deletion, maternal uniparental disomy, or imprinting defect, confirmed by fluorescent in situ hybridization, chromosomal microarray, and/or methylation studies. Obese male or female participants weighing at least 50 kilograms (kg) with body mass index (BMI) ≥ 27 kilogram per square meter (kg/m²) 2. Age 16-65 years 3. If a participant has diagnosis of type 2 diabetes, following criteria must be met: 1. hemoglobin A1C (HbA1c) \< 7.5% not being managed with insulin. Participants taking glucagon-like peptide-1 (GLP-1) analogues (exenatide or liraglutide) must have been on stable dose for greater than 3 months. 2. Fasting plasma glucose \< 140 milligrams per deciliter (mg/dL) 3. No history of ketoacidosis or hyperosmolar coma 4. Vital signs must be within the following ranges and stable. 1. Systolic blood pressure, 90-150 millimeter of mercury (mm Hg) 2. Diastolic blood pressure, 50-90 mm Hg 3. Pulse rate, 40-100 beats per minute (bpm) 5. Stable body weight at home for approximately 2 months (self or guardian-reported loss/gain within ± 5%). 6. Blood pressure (≤ 150/90 mmHg); may include stable dose (≥ 30 days of use) of up to two anti-hypertensive medications that are intended to remain on a stable dose during the protocol 7. Parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and be able to understand and sign the written informed consent. Due to the significant intellectual disability with PWS, assent is to be provided by the participant who cannot consent for himself or herself. 8. Results of screening clinical laboratory tests (complete blood count with differential and platelets and chemistry profile) must be within normal range or, if outside of the normal range, must be accepted by the investigator and sponsor as not clinically significant. 9. Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months (and confirmed with a screening follicle-stimulating hormone (FSH) level in the post-menopausal lab range), do not require contraception during the study. All other females of child-bearing potential must agree to use contraception as outlined in the protocol. 10. Males with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study and for 90 days following the study. Male participants must not donate sperm for 90 days following their participation in the study. 11. Participants must be on a stable dose of any allowed chronic concomitant medications while participating in the study.
Exclusion criteria
1. Recent use (within 3 month) of weight loss agents including herbal medication. 2. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) disorders which the investigator believes will interfere significantly with study compliance. 3. A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15. 4. Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS). 5. Clinically significant illness in the 8 weeks before screening. 6. History of clinically significant bleeding disorders. 7. Current, clinically significant liver, renal, pulmonary, cardiac, oncologic, or gastrointestinal disease. 8. Diagnosis of type 1 diabetes mellitus or other active endocrine disorders (e.g., Cushing syndrome, or thyroid dysfunction except if on adequate thyroid or glucocorticoid replacement supplement). 9. Cardiovascular disease event including history of congestive heart failure, coronary artery disease, myocardial infarction, second degree or greater heart block or prolonged QT syndrome. 10. Blood pressure \> 150/90 mm Hg. 11. Liver disease or liver injury as indicated by abnormal liver function tests, aspartate aminotransferase, alkaline phosphatase, or serum bilirubin (\> 1.5 x upper limit of normal for any of these tests) or history of hepatic cirrhosis. 12. History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine, blood urea nitrogen, or urinary constituents (e.g., albuminuria) or moderate to severe renal dysfunction as defined by the Cockcroft-Gault equation (\< 50 mL/min). 13. History or close family history (parents or siblings) of melanoma. 14. Oculocutaneous albinism (occurs at approximately 1% in PWS). 15. Significant dermatologic findings as part of the Screening comprehensive skin evaluation performed by the dermatologist. 16. Significant history of abuse of drugs or solvents in the year before screening or a positive Drugs of Abuse (DOA) test at screening. 17. History of alcohol abuse in the past year before screening or currently drinks in excess of 21 units per week (3 servings or units/day). 18. Caffeine consumption exceeding 6 cups of caffeinated tea/coffee (or equivalent) per day. 19. Participant is, in the opinion of the Investigator, not suitable to participate in the study. 20. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing. 21. Positive history for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C tests or tuberculosis. 22. Serious adverse reaction or significant hypersensitivity to any drug. 23. Clinically significant blood loss or blood donation \> 500 milliliters (mL) within 3 months. 24. Inadequate venous access. 25. History of low blood counts or recurring infections.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Body Weight - Period 2 | Baseline (Day 15) | — |
| Percent Change From Baseline in Body Weight - Period 2 | Baseline (Day 15) and Day 42 | — |
| Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 | Days 15 to 41 | An adverse event (AE) was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect |
| Number of Participants Who Experienced a TEAE - Period 3 | Days 42 to 55 | An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. An SAE was any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect |
| Number of Participants Who Experienced a TEAE - Period 4 | Days 56 to 69 | An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. An SAE was any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect |
| Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | Baseline (Day 15) | The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia). |
| Percent Change From Baseline in Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | Baseline (Day 15) and Day 42 | The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia). Percent change from baseline in overall score of PWS hyperphagia questionnaire is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Setmelanotide Trough Concentrations | 5 minutes predose on Day 42 and Day 70 | The average of setmelanotide trough concentrations values for both timepoints (5 minutes predose on Day 42 and Day 70) is presented. |
| Maximum Drug Concentration (Cmax) of Setmelanotide During a 24-Hour Steady-State Interval | Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing | Maximum drug concentration determined directly from individual concentration-time data. |
| Time to the Maximum Drug Concentration (Tmax) of Setmelanotide During a 24-Hour Steady-State Interval | Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing | Maximum drug concentration determined directly from individual concentration-time data. |
| Area Under the Drug Concentration-Time Curve From Time-Zero to 24 Hours Postdose (AUC24h) of Setmelanotide During a 24-Hour Steady-State Interval | Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing | — |
| Volume of Distribution (Vd) of Setmelanotide During a 24-Hour Steady-State Interval | Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing | Volume of distribution calculated as Dose/The observed terminal rate constant\*AUC24h. |
| Total Clearance (CL) of Setmelanotide During a 24-Hour Steady-State Interval | Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing | Clearance after extravascular administration; calculated as Dose/AUC24h. |
| Change From Baseline in Body Weight - Period 2 | Baseline (Day 15) and Day 42 | — |
| Percent Change From Baseline in Body Weight - Period 3 | Baseline (Day 42) and Day 56 | — |
| Percent Change From Baseline in Body Weight - Period 4 | Baseline (Day 56) and Day 70 | — |
| Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3 | Baseline (Day 15), Day 42, Day 56 | — |
| Percent Change From Baseline in Body Fat Measured Using Dual x-Ray Absorptiometry (DEXA) - Period 2 | Baseline (Day 15) and Day 42 | Total body fat was assessed by DEXA scan. |
| Number of Participants With Clinically Significant Percent Change From Baseline in Body Fat Measured Using DEXA - Period 4 | Baseline (Day 56) and Day 70 | Total body fat was assessed by DEXA scan. Number of participants with clinically significant percent change from baseline in body fat were judged by investigator. |
| Percent Change From Baseline in Body Mass Measured Using DEXA - Period 2 | Baseline (Day 15) and Day 42 | Total body mass was assessed by DEXA scan. |
| Number of Participants With Clinically Significant Percent Change From Baseline in Body Mass Measured Using DEXA - Period 4 | Baseline (Day 56) and Day 70 | Total body mass was assessed by DEXA scan. Number of participants with clinically significant percent change from baseline in body mass were judged by investigator. |
| Percent Change From Baseline in Hyperphagic Drive Score of PWS Hyperphagia Questionnaire - Period 2 | Baseline (Day 15) and Day 42 | The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Hyperphagic drive score assesses the persistence in asking for food based on 4 items. All 4 items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic drive range from a minimum score of 4 (no hyperphagic drive) to a maximum score of 20 (greater hyperphagic drive). Percent change from baseline in hyperphagic drive score of PWS hyperphagia questionnaire is presented. |
| Percent Change From Baseline in Hyperphagic Behaviors Score of PWS Hyperphagia Questionnaire - Period 2 | Baseline (Day 15) and Day 42 | The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Hyperphagic behavior factor score assesses food seeking behaviors based on 4 items. All 4 items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic behaviors range from a minimum score of 4 (no hyperphagic behavior) to a maximum score of 20 (greater hyperphagic behavior). Percent change from baseline in hyperphagic behaviors score of PWS hyperphagia questionnaire is presented. |
| Percent Change From Baseline in Hyperphagic Severity Score of PWS Hyperphagia Questionnaire - Period 2 | Baseline (Day 15) and Day 42 | The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Hyperphagic severity factor score assesses the severity of hyperphagia based on 2 items. Both items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic severity range from a minimum score of 2 (no hyperphagic severity) to a maximum score of 10 (greater hyperphagic severity). Percent change from baseline in hyperphagic severity score of PWS hyperphagia questionnaire is presented. |
| Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 3 | Baseline (Day 42) and Day 56 | The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia). Percent change from baseline in overall score of PWS hyperphagia questionnaire is presented. |
| Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 4 | Baseline (Day 56) and Day 70 | The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia). Percent change from baseline in overall score of PWS hyperphagia questionnaire is presented. |
Countries
United States
Participant flow
Pre-assignment details
Of the 44 participants screened, 40 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Setmelanotide 0.5 mg Participants received placebo matched to setmelanotide once daily as a subcutaneous injection from Day 1 to Day 14 (2-week, single-blind placebo run-in period); thereafter, participants received setmelanotide 0.5 milligrams (mg) once daily as a subcutaneous injection from Day 15 to Day 41 (4-week, double-blind randomized treatment period) and Day 42 to Day 55 (2-week, randomized withdrawal period). | 4 |
| Setmelanotide 1.5 mg Participants received placebo matched to setmelanotide once daily as a subcutaneous injection from Day 1 to Day 14 (2-week, single-blind placebo run-in period); thereafter, participants received setmelanotide 1.5 once daily as a subcutaneous injection from Day 15 to Day 41 (4-week, double-blind randomized treatment period), Day 42 to Day 55 (2-week, randomized withdrawal period), and Day 56 to Day 69 (optional 2-week, open-label extension period). | 13 |
| Setmelanotide 2.5 mg Participants received placebo matched to setmelanotide once daily as a subcutaneous injection from Day 1 to Day 14 (2-week, single-blind placebo run-in period); thereafter, participants received setmelanotide 2.5 once daily as a subcutaneous injection from Day 15 to Day 41 (4-week, double-blind randomized treatment period), Day 42 to Day 55 (2-week, randomized withdrawal period), and Day 56 to Day 69 (optional 2-week, open-label extension period). | 8 |
| Placebo Participants received placebo matched to setmelanotide once daily as a subcutaneous injection from Day 1 to Day 14 (2-week, single-blind placebo run-in period), Day 15 to Day 41 (4-week, double-blind randomized treatment period), and Day 42 to Day 55 (2-week, randomized withdrawal period). | 15 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Randomized Period 2 (4 Wks) | Withdrawal by participant and Investigator decision | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Setmelanotide 0.5 mg | Setmelanotide 1.5 mg | Setmelanotide 2.5 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 21.3 years STANDARD_DEVIATION 4.19 | 24.1 years STANDARD_DEVIATION 5.42 | 25.0 years STANDARD_DEVIATION 9.62 | 30.5 years STANDARD_DEVIATION 11.97 | 26.4 years STANDARD_DEVIATION 9.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 13 Participants | 7 Participants | 14 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 9 Participants | 8 Participants | 15 Participants | 36 Participants |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 6 Participants | 7 Participants | 21 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 2 Participants | 8 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 13 | 0 / 8 | 0 / 15 | 0 / 3 | 0 / 10 | 0 / 5 | 0 / 20 | 0 / 22 | 0 / 16 | 0 / 1 |
| other Total, other adverse events | 4 / 4 | 11 / 13 | 6 / 8 | 11 / 15 | 3 / 3 | 7 / 10 | 4 / 5 | 11 / 20 | 17 / 22 | 12 / 16 | 0 / 1 |
| serious Total, serious adverse events | 0 / 4 | 0 / 13 | 0 / 8 | 0 / 15 | 0 / 3 | 0 / 10 | 0 / 5 | 0 / 20 | 0 / 22 | 0 / 16 | 0 / 1 |
Outcome results
Primary
Mean Body Weight - Period 2
Time frame: Baseline (Day 15)
Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of randomized study medication with a baseline and at least 1 postbaseline efficacy observation within Period 2. Participants were classified based on randomized treatment group, regardless of the actual treatment received. Participants in the FAS with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Mean Body Weight - Period 2 | 94.3 Kilograms (kg) | Standard Error 16.84 |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Mean Body Weight - Period 2 | 92.7 Kilograms (kg) | Standard Error 5.5 |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Mean Body Weight - Period 2 | 101.6 Kilograms (kg) | Standard Error 5.35 |
| Placebo (Double-blind Randomized Treatment) | Mean Body Weight - Period 2 | 102.2 Kilograms (kg) | Standard Error 9.16 |
Primary
Number of Participants Who Experienced a TEAE - Period 3
An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. An SAE was any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect
Time frame: Days 42 to 55
Population: Participants in the Safety Set with available data were analyzed. Participants were classified into groups based on actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 3 | Participants with at least 1 TEAE | 3 Participants |
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 3 | Participants with at least 1 SAE | 0 Participants |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 3 | Participants with at least 1 SAE | 0 Participants |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 3 | Participants with at least 1 TEAE | 7 Participants |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 3 | Participants with at least 1 TEAE | 4 Participants |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 3 | Participants with at least 1 SAE | 0 Participants |
| Placebo (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 3 | Participants with at least 1 TEAE | 11 Participants |
| Placebo (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 3 | Participants with at least 1 SAE | 0 Participants |
Primary
Number of Participants Who Experienced a TEAE - Period 4
An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. An SAE was any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect
Time frame: Days 56 to 69
Population: Participants in the Safety Set with available data were analyzed. Participants were classified into groups based on actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 4 | Participants with at least 1 TEAE | 17 Participants |
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 4 | Participants with at least 1 SAE | 0 Participants |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 4 | Participants with at least 1 TEAE | 12 Participants |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 4 | Participants with at least 1 SAE | 0 Participants |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 4 | Participants with at least 1 TEAE | 0 Participants |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a TEAE - Period 4 | Participants with at least 1 SAE | 0 Participants |
Primary
Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2
An adverse event (AE) was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect
Time frame: Days 15 to 41
Population: Safety Set. Participants were classified into groups based on actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 | Participants with at least 1 TEAE | 4 Participants |
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 | Participants with at least 1 SAE | 0 Participants |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 | Participants with at least 1 SAE | 0 Participants |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 | Participants with at least 1 TEAE | 11 Participants |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 | Participants with at least 1 TEAE | 6 Participants |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 | Participants with at least 1 SAE | 0 Participants |
| Placebo (Double-blind Randomized Treatment) | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 | Participants with at least 1 TEAE | 11 Participants |
| Placebo (Double-blind Randomized Treatment) | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 | Participants with at least 1 SAE | 0 Participants |
Primary
Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2
The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia).
Time frame: Baseline (Day 15)
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | 31.0 units on a scale | Standard Error 2.86 |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | 21.2 units on a scale | Standard Error 2.28 |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | 20.2 units on a scale | Standard Error 2.79 |
| Placebo (Double-blind Randomized Treatment) | Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | 18.7 units on a scale | Standard Error 2.33 |
Primary
Percent Change From Baseline in Body Weight - Period 2
Time frame: Baseline (Day 15) and Day 42
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 2 | -0.7 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 2 | -0.8 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 2 | 0.4 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 2 | -0.4 percent change |
p-value: 0.4295% CI: [-3.1, 2.5]Longitudinal mixed analysis of variance
p-value: 0.34895% CI: [-2.3, 1.6]Longitudinal mixed analysis of variance
p-value: 0.77995% CI: [-1.3, 2.9]Longitudinal mixed analysis of variance
Primary
Percent Change From Baseline in Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2
The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia). Percent change from baseline in overall score of PWS hyperphagia questionnaire is presented.
Time frame: Baseline (Day 15) and Day 42
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | 20.2 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | -5.2 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | -5.0 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 | -1.3 percent change |
p-value: 0.90195% CI: [-11.8, 54.8]Longitudinal mixed analysis of variance
p-value: 0.36295% CI: [-26.3, 18.5]Longitudinal mixed analysis of variance
p-value: 0.37895% CI: [-28, 20.5]Longitudinal mixed analysis of variance
Secondary
Area Under the Drug Concentration-Time Curve From Time-Zero to 24 Hours Postdose (AUC24h) of Setmelanotide During a 24-Hour Steady-State Interval
Time frame: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing
Population: Participants in the PK Evaluable Population with available data were analyzed. Because only 1 participant was analyzed in the setmelanotide 1.5 mg group, no data are reported for this group in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Area Under the Drug Concentration-Time Curve From Time-Zero to 24 Hours Postdose (AUC24h) of Setmelanotide During a 24-Hour Steady-State Interval | 569.4 hr*ng/mL | Standard Deviation 190.6 |
Secondary
Change From Baseline in Body Weight - Period 2
Time frame: Baseline (Day 15) and Day 42
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Change From Baseline in Body Weight - Period 2 | -0.6 kg |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Change From Baseline in Body Weight - Period 2 | -0.8 kg |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Change From Baseline in Body Weight - Period 2 | 0.3 kg |
| Placebo (Double-blind Randomized Treatment) | Change From Baseline in Body Weight - Period 2 | -0.4 kg |
p-value: 0.43995% CI: [-3, 2.6]Longitudinal mixed analysis of variance
p-value: 0.36695% CI: [-2.3, 1.6]Longitudinal mixed analysis of variance
p-value: 0.74495% CI: [-1.4, 2.8]Longitudinal mixed analysis of variance
Secondary
Maximum Drug Concentration (Cmax) of Setmelanotide During a 24-Hour Steady-State Interval
Maximum drug concentration determined directly from individual concentration-time data.
Time frame: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing
Population: Participants in the PK Evaluable Population with available data were analyzed. Because only 1 participant was analyzed in the setmelanotide 1.5 mg group, no data are reported for this group in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Maximum Drug Concentration (Cmax) of Setmelanotide During a 24-Hour Steady-State Interval | 39.1 ng/mL | Standard Deviation 12.2 |
Secondary
Mean Setmelanotide Trough Concentrations
The average of setmelanotide trough concentrations values for both timepoints (5 minutes predose on Day 42 and Day 70) is presented.
Time frame: 5 minutes predose on Day 42 and Day 70
Population: The Pharmacokinetic (PK) Evaluable Population was defined as all participants in the Safety Population who had evaluable plasma concentration-time profiles for setmelanotide in the substudy. One participant may have received more than one doses in different periods (eg, 0.5 mg in the Double-blind Randomized Treatment Period and 1.5 mg in the Randomized Withdrawal Period) and therefore included in multiple groups in the data presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Mean Setmelanotide Trough Concentrations | 0.790 nanograms per milliliter (ng/mL) | Standard Deviation 0.336 |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Mean Setmelanotide Trough Concentrations | 2.59 nanograms per milliliter (ng/mL) | Standard Deviation 1.51 |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Mean Setmelanotide Trough Concentrations | 5.63 nanograms per milliliter (ng/mL) | Standard Deviation 4.19 |
Secondary
Number of Participants With Clinically Significant Percent Change From Baseline in Body Fat Measured Using DEXA - Period 4
Total body fat was assessed by DEXA scan. Number of participants with clinically significant percent change from baseline in body fat were judged by investigator.
Time frame: Baseline (Day 56) and Day 70
Population: Participants in the FAS with available data were analyzed. In Period 4, one participant was randomized to setmelanotide 2.5 mg treatment group but treated with placebo. As participants in the FAS are classified based on randomized treatment group regardless of the actual treatment received, the placebo group is not included in the FAS analysis for Period 4.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Number of Participants With Clinically Significant Percent Change From Baseline in Body Fat Measured Using DEXA - Period 4 | 0 Participants |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Number of Participants With Clinically Significant Percent Change From Baseline in Body Fat Measured Using DEXA - Period 4 | 0 Participants |
Secondary
Number of Participants With Clinically Significant Percent Change From Baseline in Body Mass Measured Using DEXA - Period 4
Total body mass was assessed by DEXA scan. Number of participants with clinically significant percent change from baseline in body mass were judged by investigator.
Time frame: Baseline (Day 56) and Day 70
Population: Participants in the FAS with available data were analyzed. In Period 4, one participant was randomized to setmelanotide 2.5 mg treatment group but treated with placebo. As participants in the FAS are classified based on randomized treatment group regardless of the actual treatment received, the placebo group is not included in the FAS analysis for Period 4.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Number of Participants With Clinically Significant Percent Change From Baseline in Body Mass Measured Using DEXA - Period 4 | 0 Participants |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Number of Participants With Clinically Significant Percent Change From Baseline in Body Mass Measured Using DEXA - Period 4 | 0 Participants |
Secondary
Percent Change From Baseline in Body Fat Measured Using Dual x-Ray Absorptiometry (DEXA) - Period 2
Total body fat was assessed by DEXA scan.
Time frame: Baseline (Day 15) and Day 42
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Fat Measured Using Dual x-Ray Absorptiometry (DEXA) - Period 2 | -0.6 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Fat Measured Using Dual x-Ray Absorptiometry (DEXA) - Period 2 | -1.1 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Fat Measured Using Dual x-Ray Absorptiometry (DEXA) - Period 2 | -0.7 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Fat Measured Using Dual x-Ray Absorptiometry (DEXA) - Period 2 | -1.1 percent change |
p-value: 0.63395% CI: [-2.6, 3.6]Longitudinal mixed analysis of variance
p-value: 0.52895% CI: [-2.1, 2.3]Longitudinal mixed analysis of variance
p-value: 0.64895% CI: [-2, 2.9]Longitudinal mixed analysis of variance
Secondary
Percent Change From Baseline in Body Mass Measured Using DEXA - Period 2
Total body mass was assessed by DEXA scan.
Time frame: Baseline (Day 15) and Day 42
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Mass Measured Using DEXA - Period 2 | -0.2 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Mass Measured Using DEXA - Period 2 | -1.1 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Mass Measured Using DEXA - Period 2 | -0.3 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Mass Measured Using DEXA - Period 2 | -0.9 percent change |
p-value: 0.71295% CI: [-1.8, 3.1]Longitudinal mixed analysis of variance
p-value: 0.41495% CI: [-1.9, 1.5]Longitudinal mixed analysis of variance
p-value: 0.73295% CI: [-1.3, 2.5]Longitudinal mixed analysis of variance
Secondary
Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3
Time frame: Baseline (Day 15), Day 42, Day 56
Population: FAS population with available data were analyzed for participants who continued with the same treatment when switched from Double-blind Randomized Treatment to Randomized Withdrawal Period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3 | Percent change at Day 42 | -0.7 percent change |
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3 | Percent change at Day 56 | 0.2 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3 | Percent change at Day 56 | -0.4 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3 | Percent change at Day 42 | -0.5 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3 | Percent change at Day 42 | 0.7 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3 | Percent change at Day 56 | 0.9 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3 | Percent change at Day 42 | -0.7 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3 | Percent change at Day 56 | -1.0 percent change |
Comparison: Statistical analysis is provided for percent change from baseline at Day 56.p-value: 0.67995% CI: [-4.5, 7]Longitudinal mixed analysis of variance
Comparison: Statistical analysis is provided for percent change from baseline at Day 56.p-value: 0.64195% CI: [-3.3, 4.7]Longitudinal mixed analysis of variance
Comparison: Statistical analysis is provided for percent change from baseline at Day 56.p-value: 0.80995% CI: [-2.6, 6.4]Longitudinal mixed analysis of variance
Secondary
Percent Change From Baseline in Body Weight - Period 3
Time frame: Baseline (Day 42) and Day 56
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 3 | 1.3 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 3 | 0.0 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 3 | 0.0 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 3 | 0.2 percent change |
p-value: 0.88395% CI: [-0.7, 2.8]Longitudinal mixed analysis of variance
p-value: 0.33895% CI: [-1.3, 0.9]Longitudinal mixed analysis of variance
p-value: 0.38195% CI: [-1.6, 1.2]Longitudinal mixed analysis of variance
Secondary
Percent Change From Baseline in Body Weight - Period 4
Time frame: Baseline (Day 56) and Day 70
Population: Participants in the FAS with available data were analyzed. In Period 4, one participant was randomized to setmelanotide 2.5 mg treatment group but treated with placebo. As participants in the FAS are classified based on randomized treatment group regardless of the actual treatment received, the placebo group is not included in the FAS analysis for Period 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 4 | -0.0 percent change | Standard Deviation 0.9 |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Body Weight - Period 4 | 0.0 percent change | Standard Deviation 2.7 |
Secondary
Percent Change From Baseline in Hyperphagic Behaviors Score of PWS Hyperphagia Questionnaire - Period 2
The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Hyperphagic behavior factor score assesses food seeking behaviors based on 4 items. All 4 items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic behaviors range from a minimum score of 4 (no hyperphagic behavior) to a maximum score of 20 (greater hyperphagic behavior). Percent change from baseline in hyperphagic behaviors score of PWS hyperphagia questionnaire is presented.
Time frame: Baseline (Day 15) and Day 42
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Behaviors Score of PWS Hyperphagia Questionnaire - Period 2 | 19.1 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Behaviors Score of PWS Hyperphagia Questionnaire - Period 2 | -1.7 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Behaviors Score of PWS Hyperphagia Questionnaire - Period 2 | -3.0 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Behaviors Score of PWS Hyperphagia Questionnaire - Period 2 | -0.4 percent change |
p-value: 0.81295% CI: [-24.8, 63.8]Longitudinal mixed analysis of variance
p-value: 0.46495% CI: [-29.9, 27.4]Longitudinal mixed analysis of variance
p-value: 0.43295% CI: [-33.6, 28.4]Longitudinal mixed analysis of variance
Secondary
Percent Change From Baseline in Hyperphagic Drive Score of PWS Hyperphagia Questionnaire - Period 2
The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Hyperphagic drive score assesses the persistence in asking for food based on 4 items. All 4 items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic drive range from a minimum score of 4 (no hyperphagic drive) to a maximum score of 20 (greater hyperphagic drive). Percent change from baseline in hyperphagic drive score of PWS hyperphagia questionnaire is presented.
Time frame: Baseline (Day 15) and Day 42
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Drive Score of PWS Hyperphagia Questionnaire - Period 2 | 27.2 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Drive Score of PWS Hyperphagia Questionnaire - Period 2 | -3.6 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Drive Score of PWS Hyperphagia Questionnaire - Period 2 | -6.8 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Drive Score of PWS Hyperphagia Questionnaire - Period 2 | 6.6 percent change |
p-value: 0.8495% CI: [-20.9, 62.2]Longitudinal mixed analysis of variance
p-value: 0.23695% CI: [-38.7, 18.4]Longitudinal mixed analysis of variance
p-value: 0.19195% CI: [-44.2, 17.4]Longitudinal mixed analysis of variance
Secondary
Percent Change From Baseline in Hyperphagic Severity Score of PWS Hyperphagia Questionnaire - Period 2
The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Hyperphagic severity factor score assesses the severity of hyperphagia based on 2 items. Both items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic severity range from a minimum score of 2 (no hyperphagic severity) to a maximum score of 10 (greater hyperphagic severity). Percent change from baseline in hyperphagic severity score of PWS hyperphagia questionnaire is presented.
Time frame: Baseline (Day 15) and Day 42
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Severity Score of PWS Hyperphagia Questionnaire - Period 2 | 33.2 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Severity Score of PWS Hyperphagia Questionnaire - Period 2 | -0.7 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Severity Score of PWS Hyperphagia Questionnaire - Period 2 | 5.5 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Hyperphagic Severity Score of PWS Hyperphagia Questionnaire - Period 2 | -16.7 percent change |
p-value: 0.98895% CI: [6.7, 93.2]Longitudinal mixed analysis of variance
p-value: 0.85995% CI: [-13.7, 45.6]Longitudinal mixed analysis of variance
p-value: 0.91695% CI: [-9.8, 54.3]Longitudinal mixed analysis of variance
Secondary
Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 3
The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia). Percent change from baseline in overall score of PWS hyperphagia questionnaire is presented.
Time frame: Baseline (Day 42) and Day 56
Population: Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 3 | 35.0 percent change |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 3 | -1.8 percent change |
| Setmelanotide 2.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 3 | 3.4 percent change |
| Placebo (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 3 | 2.3 percent change |
p-value: 0.94395% CI: [-8.4, 73.8]Longitudinal mixed analysis of variance
p-value: 0.33995% CI: [-24.4, 16.1]Longitudinal mixed analysis of variance
p-value: 0.53395% CI: [-25, 27.2]Longitudinal mixed analysis of variance
Secondary
Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 4
The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (no hyperphagia) to a maximum score of 50 (greater hyperphagia). Percent change from baseline in overall score of PWS hyperphagia questionnaire is presented.
Time frame: Baseline (Day 56) and Day 70
Population: Participants in the FAS with available data were analyzed. In Period 4, one participant was randomized to setmelanotide 2.5 mg treatment group but treated with placebo. As participants in the FAS are classified based on randomized treatment group regardless of the actual treatment received, the placebo group is not included in the FAS analysis for Period 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 4 | -0.9 percent change | Standard Deviation 23.21 |
| Setmelanotide 1.5 mg (Double-blind Randomized Treatment) | Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 4 | -0.4 percent change | Standard Deviation 29.94 |
Secondary
Time to the Maximum Drug Concentration (Tmax) of Setmelanotide During a 24-Hour Steady-State Interval
Maximum drug concentration determined directly from individual concentration-time data.
Time frame: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing
Population: Participants in the PK Evaluable Population with available data were analyzed. Because only 1 participant was analyzed in the setmelanotide 1.5 mg group, no data are reported for this group in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Time to the Maximum Drug Concentration (Tmax) of Setmelanotide During a 24-Hour Steady-State Interval | 6.00 hours (hr) |
Secondary
Total Clearance (CL) of Setmelanotide During a 24-Hour Steady-State Interval
Clearance after extravascular administration; calculated as Dose/AUC24h.
Time frame: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing
Population: Participants in the PK Evaluable Population with available data were analyzed. Because only 1 participant was analyzed in the setmelanotide 1.5 mg group, no data are reported for this group in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Total Clearance (CL) of Setmelanotide During a 24-Hour Steady-State Interval | 4.77 L/hr | Standard Deviation 1.49 |
Secondary
Volume of Distribution (Vd) of Setmelanotide During a 24-Hour Steady-State Interval
Volume of distribution calculated as Dose/The observed terminal rate constant\*AUC24h.
Time frame: Starting on any day from Day 63 through 69, a 24-hour PK profile obtained; blood samples were collected at 0 (within 5 minutes predose), 1, 2, 4, 6, 7, 8, 9, 10, 12, and 24 hours after dosing
Population: Participants in the PK Evaluable Population with available data were analyzed. Because only 1 participant was analyzed in the setmelanotide 1.5 mg group, no data are reported for this group in order to protect and maintain participant privacy/confidentiality.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Setmelanotide 0.5 mg (Double-blind Randomized Treatment) | Volume of Distribution (Vd) of Setmelanotide During a 24-Hour Steady-State Interval | 52.8 Liters (L) | Standard Deviation 10 |