Study of Setmelanotide Effects on QTc (Corrected QT) Interval in Healthy Subjects

Study Overview
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Brief Summary
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This is a double-blind, randomized, placebo- and positive-controlled, parallel group, 3-arm study to assess the potential for therapeutic and supratherapeutic concentrations of setmelanotide to affect the QTcF interval compared with placebo.

Official Title
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A Randomized, Double-Blind, 3-arm, Parallel Group, Placebo- and Positive-controlled Study to Investigate the Effects of Setmelanotide on QTc Interval in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Setmelanotide
* Drug: Moxifloxacin
* Drug: Oral Placebo
* Drug: SC Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between 18 and 50 years of age, inclusive. Subject has body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive. Subject is in good health, as confirmed by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, clinical laboratory evaluations, and liver function tests at Screening and Check-in. Female participants of childbearing potential must be confirmed non-pregnant and agree to use contraception. Male participants with female partners of childbearing potential must agree to use contraception. Male subjects must also not donate sperm during and for 90 days following their participation in the study. Subject is a nonsmoker (for at least 3 months) with negative urinary cotinine test at Screening and agrees to abstain from alcohol, recreational drugs (including marijuana), and tobacco or nicotine-containing products for the duration of the study. Subject is able to comprehend and is willing to sign an informed consent form and abide by the study restrictions. Exclusion Criteria: Subject has sustained systolic blood pressure (SBP) >150 mmHg or <90 mmHg or a diastolic blood pressure (DBP) >100 mmHg or <60 mmHg in the supine position at Screening or Day 1 of each study period, respectively. Subject has supine pulse rate of <45 beats per minute (bpm) or >100 bpm. Subject has abnormal screening ECG indicating a second- or third-degree atrioventricular block, or one or more of the following: QRS>110 msec, QTcF >450 msec for males and >470 msec for females, PR interval >200 msec. Subject has a history of risk factors for Torsades de Pointes (TdP), including unexplained syncope, diagnosis or family history of Brugada syndrome or long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesaemia. Glomerular filtration rate (GFR) <60 mL/min at Screening. Subject has significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion). Subject has history or close family history (parents or siblings) of melanoma or subject history of ocular-cutaneous albinism. Subject has significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator). Subject has suicidal ideation of type 4 or 5 on the C-SSRS at Screening, a history of a suicide attempt in the last 20 years, or any suicidal behavior in the last month. Subject has participated in any clinical study with an investigational drug/device within 30 days (or 5 half-lives) prior to the first day of dosing. Subject was previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide. Subject has inability to comply with QD injection regimen. Female subjects who are breastfeeding or nursing. Subject has cognitive impairment that, in the Investigator's opinion, precludes participation to the study. Subject is, in Investigator's opinion, otherwise not suitable to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Setmelanotide 7 mg<br>SC setmelanotide 7 mg; oral placebo on Days 10 and 16 | Drug: Setmelanotide<br>* Subcutaneous (SC) setmelanotide: SC injection: 2 mg × 7 days followed by 3, 5, and 7 mg × 3 days per dose level<br>Drug: Oral Placebo<br>* Placebo capsules for oral administration (identical in appearance to oral moxifloxacin treatment)<br>|
| Active Comparator: Group 2: Active placebo (Day 10)<br>SC placebo; oral moxifloxacin (positive control) on Day 10 and oral placebo on Day 16 | Drug: Moxifloxacin<br>* Moxifloxacin 400 mg capsules for oral administration (active comparator)<br>Drug: Oral Placebo<br>* Placebo capsules for oral administration (identical in appearance to oral moxifloxacin treatment)<br>Drug: SC Placebo<br>* Placebo for SC injection (vehicle only; identical in appearance to SC setmelanotide treatment)<br>|
| Active Comparator: Group 3: Active placebo (Day 16)<br>SC placebo; oral placebo on Day 10 and oral moxifloxacin on Day 16 | Drug: Moxifloxacin<br>* Moxifloxacin 400 mg capsules for oral administration (active comparator)<br>Drug: Oral Placebo<br>* Placebo capsules for oral administration (identical in appearance to oral moxifloxacin treatment)<br>Drug: SC Placebo<br>* Placebo for SC injection (vehicle only; identical in appearance to SC setmelanotide treatment)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Setmelanotide concentration-related change from baseline in QTc | Setmelanotide concentration-related change from baseline (Δ) in QTc and placebo-adjusted change from baseline (ΔΔ) in QTc corrected for HR (heart rate) using QTcF (ΔQTcF and ΔΔQTcF). | 16 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HR | Change from baseline (Δ) and placebo-corrected change from baseline (ΔΔ) in HR after administration of SC setmelanotide or oral moxifloxacin. | 16 Days | 
| Change from baseline in QTcF, PR, and QRS intervals | Change from baseline (Δ) and placebo-corrected change from baseline (ΔΔ) in QTcF, PR, and QRS intervals after administration of SC setmelanotide or oral moxifloxacin. | 16 Days | 
| Categorical outliers for HR | Categorical outliers for HR after administration of SC setmelanotide. | 16 Days | 
| Categorical outliers for QTcF, HR, PR, and QRS intervals | Categorical outliers for QTcF, HR, PR, and QRS intervals after administration of SC setmelanotide. | 16 Days | 
| Frequency of treatment-emergent changes of T-wave morphology and U-wave presence | Frequency of treatment-emergent changes of T-wave morphology and U-wave presence after administration of SC setmelanotide. | 16 Days | 
| Relationship between moxifloxacin concentrations and ΔΔQTcF | Impact on ΔΔQTcF (cmax) following single dose of moxifloxacin | 16 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers