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

NCT ID: NCT05046132

Last Updated: 2024-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-05
• Study Completion Date: 2022-04-07

Brief Summary

This was a double-blind, randomized, placebo- and positive-controlled, parallel group, 3-arm study that assessed the potential for therapeutic and supratherapeutic concentrations of setmelanotide to affect the QTc corrected by the Fredericia method (QTcF) interval.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group 1: Setmelanotide 2-7 mg + Placebo for Moxifloxacin

Participants received titrated doses of 2-7 milligrams (mg) setmelanotide once daily by subcutaneous (SC) injection, starting with a dose of 2 mg from Days 1 to 7, 3 mg from Days 8 to 10, 5 mg from Days 11 to 13 and 7 mg from Days 14 to 16. Participants also received single oral dose of placebo matching moxifloxacin on Days 10 and 16.

Group Type: EXPERIMENTAL

Setmelanotide

Intervention Type: DRUG

Administered once daily via SC injection.

Oral Placebo

Intervention Type: DRUG

Placebo capsules via oral administration.

Group 2: Placebo for Setmelanotide + Moxifloxacin 400 mg + Placebo for Moxifloxacin

Participants received placebo matching setmelanotide once daily by SC injection from Days 1 to 16. Participants also received a single oral dose of 400 mg moxifloxacin on Day 10 and a single oral dose of placebo matching moxifloxacin on Day 16.

Group Type: ACTIVE_COMPARATOR

Moxifloxacin

Intervention Type: DRUG

Moxifloxacin capsules via oral administration.

Oral Placebo

Intervention Type: DRUG

Placebo capsules via oral administration.

SC Placebo

Intervention Type: DRUG

Placebo via SC injection.

Group 3: Placebo for Setmelanotide + Placebo for Moxifloxacin + Moxifloxacin 400 mg

Participants received placebo matching setmelanotide once daily by SC injection from Days 1 to 16. Participants also received a single oral dose of placebo matching moxifloxacin on Day 10 and a single oral dose of 400 mg moxifloxacin on Day 16.

Group Type: ACTIVE_COMPARATOR

Moxifloxacin

Intervention Type: DRUG

Moxifloxacin capsules via oral administration.

Oral Placebo

Intervention Type: DRUG

Placebo capsules via oral administration.

SC Placebo

Intervention Type: DRUG

Placebo via SC injection.

Interventions

Setmelanotide

Administered once daily via SC injection.

Intervention Type: DRUG

Moxifloxacin

Moxifloxacin capsules via oral administration.

Intervention Type: DRUG

Oral Placebo

Placebo capsules via oral administration.

Intervention Type: DRUG

SC Placebo

Placebo via SC injection.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant has body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m^2), inclusive.
• Participant is in good health, as confirmed by no clinically significant findings from medical history, physical examination, 12-lead Electrocardiogram (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 participants must also not donate sperm during and for 90 days following their participation in the study.
• Participant 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.
• Participant is able to comprehend and is willing to sign an informed consent form and abide by the study restrictions.

Exclusion Criteria

• Participant has sustained systolic blood pressure (SBP) >150 millimeters of mercury (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.
• Participant has supine pulse rate of <45 beats per minute (bpm) or >100 bpm.
• Participant has abnormal screening ECG indicating a second- or third-degree atrioventricular block, or one or more of the following: QRS>110 millisecond (msec) , QTcF >450 msec for males and >470 msec for females, PR interval >200 msec.
• Participant 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 milliliter per minute (mL/min) at Screening.
• Participant has significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion).
• Participant has history or close family history (parents or siblings) of melanoma or participant history of ocular-cutaneous albinism.
• Participant 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).
• Participant has suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening, a history of a suicide attempt in the last 20 years, or any suicidal behavior in the last month.
• Participant 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.
• Participant was previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
• Participant has inability to comply with once daily dosing (QD) injection regimen.
• Female participants who are breastfeeding or nursing.
• Participant has cognitive impairment that, in the investigator's opinion, precludes participation to the study.
• Participant is, in investigator's opinion, otherwise not suitable to participate in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rhythm Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Meeker, MD

Role: STUDY_CHAIR

Rhythm Pharmaceuticals, Inc.

Locations

Parexel Early Phase Clinical Unit (Los Angeles)

Glendale, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

263791

Identifier Type: OTHER

Identifier Source: secondary_id

RM-493-032

Identifier Type: -

Identifier Source: org_study_id