Phase 2 Trial to Evaluate Safety and Efficacy of Setmelanotide (RM-493) in Obese Participants With Prader-Willi Syndrome
Official Title
A Phase 2, Randomized, Double-Blind, Placebo-controlled Pilot Study to Assess the Effects of RM-493, a Melanocortin 4 Receptor (MC4R) Agonist, in Obese Subjects With Prader-Willi Syndrome (PWS) on Safety, Weight Reduction, and Food-Related Behaviors
Acronym
Not provided
Organization
Rhythm Pharmaceuticals, Inc.INDUSTRY
Status Module
Record Verification Date
Jul 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 19, 2015Actual
Primary Completion Date
Oct 26, 2016Actual
Completion Date
Oct 26, 2016Actual
First Submitted Date
Nov 25, 2014
First Submission Date that Met QC Criteria
Dec 4, 2014
First Posted Date
Dec 8, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
May 18, 2023
Results First Submitted that Met QC Criteria
Jul 6, 2023
Results First Posted Date
Jul 27, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 29, 2018
Certification/Extension First Submitted that Passed QC Review
Jan 30, 2018
Certification/Extension First Posted Date
Jan 31, 2018Actual
Last Update Submitted Date
Jul 6, 2023
Last Update Posted Date
Jul 27, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Rhythm Pharmaceuticals, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
Not provided
Conditions Module
Conditions
Prader-Willi Syndrome
Keywords
Prader-Willi Syndrome
obesity
hyperphagia
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
40Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Setmelanotide 0.5 mg
Experimental
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).
Drug: Setmelanotide
Setmelanotide 1.5 mg
Experimental
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).
Drug: Setmelanotide
Setmelanotide 2.5 mg
Experimental
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).
Drug: Setmelanotide
Placebo
Placebo Comparator
Participants received placebo matched to setmelanotide once daily as a subcutaneous injection from Day 1 to Day 14 (2-week, single-blind 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).
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Setmelanotide
Drug
subcutaneous injection
Setmelanotide 0.5 mg
Setmelanotide 1.5 mg
Setmelanotide 2.5 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
Days 15 to 41
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
Days 42 to 55
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
Secondary Outcomes
Measure
Description
Time Frame
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
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)
Age 16-65 years
If a participant has diagnosis of type 2 diabetes, following criteria must be met:
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.
Fasting plasma glucose < 140 milligrams per deciliter (mg/dL)
No history of ketoacidosis or hyperosmolar coma
Vital signs must be within the following ranges and stable.
Systolic blood pressure, 90-150 millimeter of mercury (mm Hg)
Diastolic blood pressure, 50-90 mm Hg
Pulse rate, 40-100 beats per minute (bpm)
Stable body weight at home for approximately 2 months (self or guardian-reported loss/gain within ± 5%).
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
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.
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.
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.
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.
Participants must be on a stable dose of any allowed chronic concomitant medications while participating in the study.
Exclusion Criteria:
Recent use (within 3 month) of weight loss agents including herbal medication.
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.
A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15.
Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS).
Clinically significant illness in the 8 weeks before screening.
History of clinically significant bleeding disorders.
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).
Cardiovascular disease event including history of congestive heart failure, coronary artery disease, myocardial infarction, second degree or greater heart block or prolonged QT syndrome.
Blood pressure > 150/90 mm Hg.
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.
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).
History or close family history (parents or siblings) of melanoma.
Oculocutaneous albinism (occurs at approximately 1% in PWS).
Significant dermatologic findings as part of the Screening comprehensive skin evaluation performed by the dermatologist.
Significant history of abuse of drugs or solvents in the year before screening or a positive Drugs of Abuse (DOA) test at screening.
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).
Caffeine consumption exceeding 6 cups of caffeinated tea/coffee (or equivalent) per day.
Participant is, in the opinion of the Investigator, not suitable to participate in the study.
Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
Positive history for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C tests or tuberculosis.
Serious adverse reaction or significant hypersensitivity to any drug.
Clinically significant blood loss or blood donation > 500 milliliters (mL) within 3 months.
Inadequate venous access.
History of low blood counts or recurring infections.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
16 Years
Maximum Age
65 Years
Standard Ages
ChildAdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
David Meeker
Rhythm Pharmaceuticals, Inc.
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
University of California Irvine
Irvine
California
92617
United States
University of Florida
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Of the 44 participants screened, 40 participants were enrolled in the study.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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).
Percent Change From Baseline in Body Weight - Period 2
Baseline (Day 15) and Day 42
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).
Baseline (Day 15)
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.
Baseline (Day 15) and Day 42
Baseline (Day 15) and Day 42
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.
Baseline (Day 15) and Day 42
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.
Baseline (Day 15) and Day 42
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.
Baseline (Day 42) and Day 56
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.
Baseline (Day 56) and Day 70
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.
5 minutes predose on Day 42 and Day 70
Maximum Drug Concentration (Cmax) of Setmelanotide During a 24-Hour Steady-State Interval
Maximum drug concentration determined directly from individual concentration-time data.
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
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.
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
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
Volume of distribution calculated as Dose/The observed terminal rate constant*AUC24h.
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
Total Clearance (CL) of Setmelanotide During a 24-Hour Steady-State Interval
Clearance after extravascular administration; calculated as Dose/AUC24h.
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
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
Total body fat was assessed by DEXA scan.
Baseline (Day 15) and Day 42
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.
Baseline (Day 56) and Day 70
Percent Change From Baseline in Body Mass Measured Using DEXA - Period 2
Total body mass was assessed by DEXA scan.
Baseline (Day 15) and Day 42
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.
Baseline (Day 56) and Day 70
Gainesville
Florida
32610
United States
Kansas University Medical Center
Kansas City
Kansas
66160
United States
Winthrop University Hospital
Mineola
New York
11501
United States
Vanderbilt University
Nashville
Tennessee
37203
United States
FG001
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).
FG002
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).
FG003
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).
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00340 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00340 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Double-blind Randomized Period 2 (4 Wks)
Type
Comment
Milestone Data
STARTED
Forty participants who completed placebo single-blind run-in period entered the double-blind randomized treatment period. Fifteen participants continued placebo and 25 participants were randomized to other treatment groups in the double-blind randomized treatment period.
FG0004 subjects
FG00113 subjectsOne participant was randomized to setmelanotide 2.5 mg treatment group and treated with setmelanotide 1.5 mg group.
FG0028 subjects
FG00315 subjectsOne participant was randomized to setmelanotide 2.5 mg treatment group and treated with placebo.
COMPLETED
FG0004 subjects
FG00113 subjects
FG0027 subjects
FG00315 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
Type
Comment
Reasons
Withdrawal by participant and Investigator decision
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG003
Randomized Withdrawal Period 3 (2 Weeks)
Type
Comment
Milestone Data
STARTED
After completion of Period 2, a randomized withdrawal (Period 3) was initiated; participants within each of the setmelanotide groups were randomized 1:1; participants who had received setmelanotide were either continued at the current active dose, or switched to placebo treatment. Participants administered placebo during Period 2 were randomized 1:1 in Period 3 and either continued to receive placebo or began to receive setmelanotide.
FG0003 subjects
FG00110 subjects
FG0025 subjects
FG00320 subjects
COMPLETED
FG0003 subjects
FG00110 subjects
FG0025 subjects
FG00320 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Open-label Extension Period 4 (2 Weeks)
Type
Comment
Milestone Data
STARTED
Period 4 was a follow-up, open-label extension available to participants who completed the first 3 periods and wanted to continue treatment. In Period 4, all participants were to receive either setmelanotide 1.5 mg or setmelanotide 2.5 mg.
FG0000 subjects
FG00122 subjectsThree participants were randomized to setmelanotide 2.5 mg treatment group and treated with setmelanotide 1.5 mg.
FG00216 subjects
FG0031 subjectsOne participant advanced from the Double-blind Randomized Treatment Period (Period 2) to the Open-Label Extension Period (Period 4) due to an error in the interactive voice response system (IVRS); therefore, results are presented for 38 participants in Randomized Withdrawal Period (Period 3) but 39 participants in the Open-Label Extension Period (Period 4).
The participant was randomized to setmelanotide 2.5 mg treatment group and treated with placebo.
COMPLETED
FG0000 subjects
FG00122 subjects
FG00216 subjects
FG0031 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Safety Set included all randomized participants who received at least 1 dose of study medication, and had at least one post-dose safety assessment (within Period 2). Participants were classified into groups based on actual treatment received.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
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).
BG001
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).
BG002
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).
BG003
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).
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0004
BG00113
BG0028
BG00315
BG00440
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00021.3± 4.19
BG00124.1± 5.42
BG00225.0± 9.62
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG0016
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0002
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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
Safety Set. Participants were classified into groups based on actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00113
OG0028
OG003
Title
Denominators
Categories
Participants with at least 1 TEAE
Title
Measurements
OG0004
OG00111
OG0026
OG003
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
Participants in the Safety Set with available data were analyzed. Participants were classified into groups based on actual treatment received.
Participants received setmelanotide 1.5 mg once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
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
Participants in the Safety Set with available data were analyzed. Participants were classified into groups based on actual treatment received.
Posted
Count of Participants
Participants
Days 56 to 69
ID
Title
Description
OG000
Setmelanotide 1.5 mg (Open-Label Extension)
Participants received setmelanotide 1.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
OG001
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Primary
Mean Body Weight - Period 2
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.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
Primary
Percent Change From Baseline in Body Weight - Period 2
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
Placebo (Double-blind Randomized Treatment)
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).
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
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.
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
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.
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
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.
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
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.
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
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.
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 1.5 mg once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
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.
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.
Posted
Mean
Standard Deviation
percent change
Baseline (Day 56) and Day 70
ID
Title
Description
OG000
Setmelanotide 1.5 mg (Open-Label Extension)
Participants received setmelanotide 1.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
OG001
Setmelanotide 2.5 mg (Open-Label Extension)
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.
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.
Posted
Mean
Standard Deviation
nanograms per milliliter (ng/mL)
5 minutes predose on Day 42 and Day 70
ID
Title
Description
OG000
Setmelanotide 0.5 mg
Participants received setmelanotide 0.5 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).
OG001
Setmelanotide 1.5 mg
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).
OG002
Setmelanotide 2.5 mg
Secondary
Maximum Drug Concentration (Cmax) of Setmelanotide During a 24-Hour Steady-State Interval
Maximum drug concentration determined directly from individual concentration-time data.
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.
Posted
Mean
Standard Deviation
ng/mL
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
ID
Title
Description
OG000
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Participants
OG000
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.
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.
Posted
Median
Full Range
hours (hr)
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
ID
Title
Description
OG000
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Participants
OG000
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
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.
Posted
Mean
Standard Deviation
hr*ng/mL
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
ID
Title
Description
OG000
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Participants
OG000
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.
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.
Posted
Mean
Standard Deviation
Liters (L)
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
ID
Title
Description
OG000
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Participants
OG000
Secondary
Total Clearance (CL) of Setmelanotide During a 24-Hour Steady-State Interval
Clearance after extravascular administration; calculated as Dose/AUC24h.
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.
Posted
Mean
Standard Deviation
L/hr
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
ID
Title
Description
OG000
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Participants
OG000
Secondary
Change From Baseline in Body Weight - Period 2
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
Placebo (Double-blind Randomized Treatment)
Secondary
Percent Change From Baseline in Body Weight - Period 3
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 2.5 mg once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
OG003
Placebo (Randomized Withdrawal Period)
Secondary
Percent Change From Baseline in Body Weight - Period 4
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.
Posted
Mean
Standard Deviation
percent change
Baseline (Day 56) and Day 70
ID
Title
Description
OG000
Setmelanotide 1.5 mg (Open-Label Extension)
Participants received setmelanotide 1.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
OG001
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Participants
OG000
Secondary
Percent Change From Baseline in Body Weight for Continuous Active and Continuous Placebo Treatments - Period 2 and 3
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.
Posted
Least Squares Mean
95% Confidence Interval
percent change
Baseline (Day 15), Day 42, Day 56
ID
Title
Description
OG000
Setmelanotide 0.5 mg (Double-blind Randomized Treatment, Then Randomized Withdrawal Period)
Participants received setmelanotide 0.5 mg as a subcutaneous injection once daily from Day 15 to Day 41 in a 4-week, double-blind randomized treatment period and then from Day 42 to Day 55 in a 2-week, randomized withdrawal period.
OG001
Setmelanotide 1.5 mg (Double-blind Randomized Treatment, Then Randomized Withdrawal Period)
Participants received setmelanotide 1.5 mg as a subcutaneous injection once daily from Day 15 to Day 41 in a 4-week, double-blind randomized treatment period and then from Day 42 to Day 55 in a 2-week, randomized withdrawal period.
OG002
Setmelanotide 2.5 mg (Double-blind Randomized Treatment, Then Randomized Withdrawal Period)
Participants received setmelanotide 2.5 mg as a subcutaneous injection once daily from Day 15 to Day 41 in a 4-week, double-blind randomized treatment period and then from Day 42 to Day 55 in a 2-week, randomized withdrawal period.
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.
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
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.
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.
Posted
Count of Participants
Participants
Baseline (Day 56) and Day 70
ID
Title
Description
OG000
Setmelanotide 1.5 mg (Open-Label Extension)
Participants received setmelanotide 1.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
OG001
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Secondary
Percent Change From Baseline in Body Mass Measured Using DEXA - Period 2
Total body mass was assessed by DEXA scan.
Participants in the FAS with available data were analyzed. Participants were classified based on randomized treatment group, regardless of the actual treatment received.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
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.
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.
Posted
Count of Participants
Participants
Baseline (Day 56) and Day 70
ID
Title
Description
OG000
Setmelanotide 1.5 mg (Open-Label Extension)
Participants received setmelanotide 1.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
OG001
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Time Frame
Day 15 to Day 69
Description
Safety Set; participants were classified into groups based on actual treatment received. The single-blind placebo run-in period (Day 1 to Day 14) is not part of statistical analysis of this study; therefore, no AE data were collected for this period.
Participants received setmelanotide 0.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 1.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
0
8
0
8
6
8
EG003
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 2.5 mg once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
0
5
0
5
4
5
EG007
Placebo (Randomized Withdrawal Period)
Participants received placebo matched to setmelanotide once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
0
20
0
20
11
20
EG008
Setmelanotide 1.5 mg (Open-Label Extension)
Participants received setmelanotide 1.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
0
22
0
22
17
22
EG009
Setmelanotide 2.5 mg (Open-Label Extension)
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
0
16
0
16
12
16
EG010
Placebo (Open-Label Extension)
The participant, due to an error in the IVRS, received placebo matched to setmelanotide once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
0
1
0
1
0
1
Serious Adverse Events
Not provided
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Injection site erythema
General disorders
MedDRA 18.0
Systematic Assessment
EG0003 affected4 at risk
EG0015 affected13 at risk
EG0024 affected8 at risk
EG0036 affected15 at risk
EG0042 affected3 at risk
EG0054 affected10 at risk
EG0064 affected5 at risk
EG0074 affected20 at risk
EG0088 affected22 at risk
EG0096 affected16 at risk
EG0100 affected1 at risk
Injection site induration
General disorders
MedDRA 18.0
Systematic Assessment
EG0002 affected4 at risk
EG0014 affected13 at risk
EG0022 affected8 at risk
EG003
Injection site oedema
General disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0012 affected13 at risk
EG0021 affected8 at risk
EG003
Injection site bruising
General disorders
MedDRA 18.0
Systematic Assessment
EG0003 affected4 at risk
EG0011 affected13 at risk
EG0021 affected8 at risk
EG003
Injection site pain
General disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0021 affected8 at risk
EG003
Injection site pruritus
General disorders
MedDRA 18.0
Systematic Assessment
EG0001 affected4 at risk
EG0013 affected13 at risk
EG0020 affected8 at risk
EG003
Influenza like illness
General disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Injection site discolouration
General disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Injection site nodule
General disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Injection site reaction
General disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Injection site swelling
General disorders
MedDRA 18.0
Systematic Assessment
EG0001 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Chest discomfort
General disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Injection site erosion
General disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Skin hyperpigmentation
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0021 affected8 at risk
EG003
Skin discolouration
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0001 affected4 at risk
EG0012 affected13 at risk
EG0020 affected8 at risk
EG003
Ephelides
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Ingrowing nail
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Hyperkeratosis
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Skin erosion
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Miliaria
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Seborrhoeic dermatitis
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Skin lesion
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Solar lentigo
Skin and subcutaneous tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Erection increased
Reproductive system and breast disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0021 affected8 at risk
EG003
Spontaneous penile erection
Reproductive system and breast disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Menorrhagia
Reproductive system and breast disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Genital disorder female
Reproductive system and breast disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0021 affected8 at risk
EG003
Soft tissue mass
Musculoskeletal and connective tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0021 affected8 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Aggression
Psychiatric disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Tearfulness
Psychiatric disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Abnormal behaviour
Psychiatric disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Irritability
Psychiatric disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Mood altered
Psychiatric disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Libido increased
Psychiatric disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Pigmentation lip
Gastrointestinal disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Headache
Nervous system disorders
MedDRA 18.0
Systematic Assessment
EG0002 affected4 at risk
EG0011 affected13 at risk
EG0020 affected8 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Fungal infection
Infections and infestations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Skin infection
Infections and infestations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Ear infection
Infections and infestations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Localised infection
Infections and infestations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Onychomycosis
Infections and infestations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Tinea pedis
Infections and infestations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Vaginal infection
Infections and infestations
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Scar
Injury, poisoning and procedural complications
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Heat exhaustion
Injury, poisoning and procedural complications
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Haemangioma of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Melanocytic naevus
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Hypertension
Vascular disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 18.0
Systematic Assessment
EG0000 affected4 at risk
EG0010 affected13 at risk
EG0020 affected8 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
All information regarding setmelanotide supplied by Rhythm to the investigator is privileged and confidential information. The investigator agrees to use this information to accomplish the study and will not use it for other purposes without consent from Rhythm. The information obtained from the clinical study will be used towards the development of setmelanotide and may be disclosed to regulatory authority(ies), other investigators, corporate partners, or consultants as required.
Participants received setmelanotide 2.5 mg once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
OG003
Placebo (Randomized Withdrawal Period)
Participants received placebo matched to setmelanotide once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
Units
Counts
Participants
OG0003
OG00110
OG0025
OG00320
Title
Denominators
Categories
Participants with at least 1 TEAE
Title
Measurements
OG0003
OG0017
OG0024
OG00311
Participants with at least 1 SAE
Title
Measurements
OG0000
OG0010
OG0020
OG003
OG002
Placebo (Open-Label Extension)
Participants received placebo matched to setmelanotide once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Participants
OG00022
OG00116
OG0021
Title
Denominators
Categories
Participants with at least 1 TEAE
Title
Measurements
OG00017
OG00112
OG0020
Participants with at least 1 SAE
Title
Measurements
OG0000
OG0010
OG0020
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00112
OG0029
OG00313
Title
Denominators
Categories
Title
Measurements
OG00094.3± 16.84
OG00192.7± 5.50
OG002101.6± 5.35
OG003102.2± 9.16
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00112
OG0029
OG00313
Title
Denominators
Categories
Title
Measurements
OG000-0.7(-3.1 to 1.8)
OG001-0.8(-2.2 to 0.6)
OG0020.4(-1.2 to 2.0)
OG003-0.4(-1.8 to 0.9)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.420
One sided p-value.
Least Squares (LS) Mean Difference
-0.3
2-Sided
95
-3.1
2.5
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Longitudinal mixed analysis of variance
One sided p-value.
0.348
LS Mean Difference
-0.4
2-Sided
95
-2.3
1.6
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Longitudinal mixed analysis of variance
0.779
One sided p-value.
LS Mean Difference
0.8
2-Sided
95
-1.3
2.9
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00112
OG0029
OG00313
Title
Denominators
Categories
Title
Measurements
OG00020.2(-8.7 to 49.1)
OG001-5.2(-21.3 to 10.9)
OG002-5.0(-23.7 to 13.6)
OG003-1.3(-16.9 to 14.3)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.901
One sided p-value.
LS Mean Difference
21.5
2-Sided
95
-11.8
54.8
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Longitudinal mixed analysis of variance
0.362
One sided p-value.
LS Mean Difference
-3.9
2-Sided
95
-26.3
18.5
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Longitudinal mixed analysis of variance
0.378
One sided p-value.
LS Mean Difference
-3.7
2-Sided
95
-28.0
20.5
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00112
OG0029
OG00313
Title
Denominators
Categories
Title
Measurements
OG00027.2(-8.9 to 63.3)
OG001-3.6(-24.1 to 16.9)
OG002-6.8(-30.5 to 16.8)
OG0036.6(-13.2 to 26.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.840
One sided p-value.
LS Mean Difference
20.6
2-Sided
95
-20.9
62.2
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Longitudinal mixed analysis of variance
0.236
One sided p-value.
LS Mean Difference
-10.2
2-Sided
95
-38.7
18.4
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00112
OG0029
OG00313
Title
Denominators
Categories
Title
Measurements
OG00019.1(-19.3 to 57.5)
OG001-1.7(-22.3 to 18.9)
OG002-3.0(-26.8 to 20.8)
OG003-0.4(-20.4 to 19.6)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.812
One sided p-value.
LS Mean Difference
19.5
2-Sided
95
-24.8
63.8
Other
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
OG001
OG003
Longitudinal mixed analysis of variance
0.464
One sided p-value.
LS Mean Difference
-1.3
2-Sided
95
-29.9
27.4
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Longitudinal mixed analysis of variance
0.432
One sided p-value.
LS Mean Difference
-2.6
2-Sided
95
-33.6
28.4
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Participants received setmelanotide 2.5 mg once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
OG003
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00112
OG0029
OG00313
Title
Denominators
Categories
Title
Measurements
OG00033.2(-4.4 to 70.9)
OG001-0.7(-22.1 to 20.6)
OG0025.5(-19.1 to 30.2)
OG003-16.7(-37.3 to 3.9)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.988
One sided p-value.
LS Mean Difference
49.9
2-Sided
95
6.7
93.2
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Longitudinal mixed analysis of variance
0.859
One sided p-value.
LS Mean Difference
16.0
2-Sided
95
-13.7
45.6
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Longitudinal mixed analysis of variance
0.916
One sided p-value.
LS Mean Difference
22.2
2-Sided
95
-9.8
54.3
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Participants received setmelanotide 2.5 mg once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
OG003
Placebo (Randomized Withdrawal Period)
Participants received placebo matched to setmelanotide once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
Units
Counts
Participants
OG0003
OG00110
OG0025
OG00320
Title
Denominators
Categories
Title
Measurements
OG00035.0(-2.9 to 72.9)
OG001-1.8(-18.4 to 14.7)
OG0023.4(-20.1 to 26.9)
OG0032.3(-9.6 to 14.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.943
One sided p-value.
LS Mean Difference
32.7
2-Sided
95
-8.4
73.8
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Longitudinal mixed analysis of variance
0.339
One sided p-value.
LS Mean Difference
-4.2
2-Sided
95
-24.4
16.1
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Longitudinal mixed analysis of variance
0.533
One sided p-value.
LS Mean Difference
1.1
2-Sided
95
-25.0
27.2
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
Participants received setmelanotide 2.5 mg once daily from Day 56 to Day 69 as a subcutaneous injection in an optional 2-week, open-label extension period.
Units
Counts
Participants
OG00015
OG00120
Title
Denominators
Categories
Title
Measurements
OG000-0.9± 23.21
OG001-0.4± 29.94
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).
Units
Counts
Participants
OG0004
OG00127
OG00229
Title
Denominators
Categories
Title
Measurements
OG0000.790± 0.336
OG0012.59± 1.51
OG0025.63± 4.19
7
Title
Denominators
Categories
Title
Measurements
OG00039.1± 12.2
7
Title
Denominators
Categories
Title
Measurements
OG0006.00(5.95 to 10.15)
5
Title
Denominators
Categories
Title
Measurements
OG000569.4± 190.6
5
Title
Denominators
Categories
Title
Measurements
OG00052.8± 10.0
5
Title
Denominators
Categories
Title
Measurements
OG0004.77± 1.49
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00112
OG0029
OG00313
Title
Denominators
Categories
Title
Measurements
OG000-0.6(-3.1 to 1.8)
OG001-0.8(-2.2 to 0.7)
OG0020.3(-1.4 to 1.9)
OG003-0.4(-1.8 to 1.0)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.439
One sided p-value.
LS Mean Difference
-0.2
2-Sided
95
-3.0
2.6
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Longitudinal mixed analysis of variance
0.366
One sided p-value.
LS Mean Difference
-0.3
2-Sided
95
-2.3
1.6
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Longitudinal mixed analysis of variance
0.744
One sided p-value.
LS Mean Difference
0.7
2-Sided
95
-1.4
2.8
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
Participants received placebo matched to setmelanotide once daily from Day 42 to Day 55 as a subcutaneous injection in a 2-week, randomized withdrawal period.
Units
Counts
Participants
OG0003
OG00110
OG0025
OG00320
Title
Denominators
Categories
Title
Measurements
OG0001.3(-0.3 to 2.9)
OG0010.0(-0.9 to 0.9)
OG0020.0(-1.3 to 1.3)
OG0030.2(-0.4 to 0.9)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.883
One sided p-value.
LS Mean Difference
1.0
2-Sided
95
-0.7
2.8
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Longitudinal mixed analysis of variance
0.338
One sided p-value.
LS Mean Difference
-0.2
2-Sided
95
-1.3
0.9
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Longitudinal mixed analysis of variance
0.381
One sided p-value.
LS Mean Difference
-0.2
2-Sided
95
-1.6
1.2
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
19
OG00120
Title
Denominators
Categories
Title
Measurements
OG000-0.0± 0.90
OG0010.0± 2.70
OG003
Placebo (Double-blind Randomized Treatment), Then Placebo (Randomized Withdrawal Period)
Participants received placebo matched to setmelanotide as a subcutaneous injection once daily from Day 15 to Day 41 in a 4-week, double-blind randomized treatment period and then from Day 42 to Day 55 in a 2-week, randomized withdrawal period.
Units
Counts
Participants
OG0002
OG0016
OG0024
OG0037
Title
Denominators
Categories
Percent change at Day 42
Title
Measurements
OG000-0.7(-5.3 to 3.9)
OG001-0.5(-3.1 to 2.2)
OG0020.7(-2.6 to 4.0)
OG003-0.7(-3.2 to 1.7)
Percent change at Day 56
Title
Measurements
OG0000.2(-4.8 to 5.3)
OG001-0.4(-3.3 to 2.6)
OG0020.9(-2.7 to 4.4)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Statistical analysis is provided for percent change from baseline at Day 56.
Longitudinal mixed analysis of variance
0.679
One sided p-value.
LS Mean Difference
1.3
2-Sided
95
-4.5
7.0
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Statistical analysis is provided for percent change from baseline at Day 56.
Longitudinal mixed analysis of variance
0.641
One sided p-value.
LS Mean Difference
0.7
2-Sided
95
-3.3
4.7
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Statistical analysis is provided for percent change from baseline at Day 56.
Longitudinal mixed analysis of variance
0.809
One sided p-value.
LS Mean Difference
1.9
2-Sided
95
-2.6
6.4
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG003
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00112
OG0028
OG00313
Title
Denominators
Categories
Title
Measurements
OG000-0.6(-3.4 to 2.1)
OG001-1.1(-2.7 to 0.5)
OG002-0.7(-2.6 to 1.3)
OG003-1.1(-2.7 to 0.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.633
One sided p-value.
LS Mean Difference
0.5
2-Sided
95
-2.6
3.6
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Longitudinal mixed analysis of variance
0.528
One sided p-value.
LS Mean Difference
0.1
2-Sided
95
-2.1
2.3
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Longitudinal mixed analysis of variance
0.648
One sided p-value.
LS Mean Difference
0.5
2-Sided
95
-2.0
2.9
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
Participants
OG00019
OG00120
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
Placebo (Double-blind Randomized Treatment)
Participants received placebo matched to setmelanotide once daily from Day 15 to Day 41 as a subcutaneous injection in a 4-week, double-blind randomized treatment period.
Units
Counts
Participants
OG0004
OG00112
OG0028
OG00313
Title
Denominators
Categories
Title
Measurements
OG000-0.2(-2.3 to 1.9)
OG001-1.1(-2.3 to 0.2)
OG002-0.3(-1.8 to 1.2)
OG003-0.9(-2.1 to 0.3)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Longitudinal mixed analysis of variance
0.712
One sided p-value.
LS Mean Difference
0.7
2-Sided
95
-1.8
3.1
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG001
OG003
Longitudinal mixed analysis of variance
0.414
One sided p-value.
LS Mean Difference
-0.2
2-Sided
95
-1.9
1.5
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.
Other
OG002
OG003
Longitudinal mixed analysis of variance
0.732
One sided p-value
LS Mean Difference
0.6
2-Sided
95
-1.3
2.5
A longitudinal mixed analysis of variance model with fixed effects for treatment, time, treatment-by-time interaction, treatment-by-baseline weight interaction, baseline weight as covariate and participant as random effect was used.