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Trial · Interventional

CompletedPhase 4Results postedRegistry data

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

NCTNCT05046132 (opens ClinicalTrials.gov in a new tab)Other idRM-493-032Other id263791
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 4
Enrollment
77 participants (actual)
Sponsor
Rhythm Pharmaceuticals, Inc. · Industry
Design
Randomized · Triple masking
Countries
1 country

United States

Start
5 Aug 2021
Primary completion
7 Apr 2022
Completion
7 Apr 2022
First posted
16 Sept 2021
Last update posted
3 May 2024
Conditions
Healthy

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
202120222023
  1. Ph 4

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

    NCT05046132

    5 Aug 2021 to 7 Apr 2022

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • SetmelanotideDrug
  • MoxifloxacinDrug
  • Oral PlaceboDrug
  • SC PlaceboDrug

Arms3

  • Experimental

    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.

  • Active comparator

    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.

  • Active comparator

    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.

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10

    Time frame · Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hours (hrs) postdose

    Registry description

    Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Baseline and Day 10. ECG analysts were blinded to the treatment, timepoint and participant. QT interval was corrected for heart rate using QTcF. CHFB in QTcF was calculated at each timepoint.

  2. Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16

    Time frame · Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    Continuous 12-lead digital ECG recording was performed on Baseline and Day 16. ECG analysts were blinded to the treatment, timepoint and participant. QT interval was corrected for heart rate using QTcF. CHFB in QTcF was calculated at each timepoint.

Secondary outcomes(15)

  1. Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10

    Time frame · Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hours (hrs) postdose

    Registry description

    The CHFB in HR was analyzed using an analysis of variance model (ANOVA) including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. Placebo corrected values were reported in the inferential statistics.

  2. Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16

    Time frame · Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    The CHFB in HR was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.

  3. Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10

    Time frame · Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    The CHFB in QTcF was analyzed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.

  4. Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16

    Time frame · Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    The CHFB in QTcF was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.

  5. Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10

    Time frame · Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    The CHFB in PR was analyzed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.

  6. Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16

    Time frame · Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    The CHFB in PR was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.

  7. Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10

    Time frame · Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    The CHFB in QRS was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.

  8. Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16

    Time frame · Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    The CHFB in QRS was analyzed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.

  9. Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide

    Time frame · Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)

    Registry description

    A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: HR (\<40 beats/min, HR\>120 beats/min and Relative CHFB \>25%) Relative CHFB = 100\*(Value-Baseline)/Baseline

  10. Number of Participants With at Least One Treatment-Emergent Abnormal Value in PR Intervals After Administration of SC Setmelanotide

    Time frame · Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)

    Registry description

    A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: PR (\>220 msec, Relative CHFB \>25%); Relative CHFB = 100\*(Value-Baseline)/Baseline

  11. Number of Participants With at Least One Treatment-Emergent Abnormal Value in QRS Intervals After Administration of SC Setmelanotide

    Time frame · Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)

    Registry description

    A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: QRS ( \>120 msec, Relative CHFB \>25%); Relative CHFB = 100\*(Value-Baseline)/Baseline

  12. Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide

    Time frame · Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)

    Registry description

    A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: QTcF (450\<QTc\<=480 msec, 480\<QTc\<=500 msec, QTc\>500 msec, 30\<CHFB in QTc\<=60 msec, CHFB in \>60 msec)

  13. Number of Participants With at Least One Treatment-Emergent Abnormal Finding in T-wave Morphology and U-wave Presence After Administration of SC Setmelanotide

    Time frame · Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)

    Registry description

    A treatment-emergent abnormality/finding will be defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included : QTcF Increase From Baseline, \> 30 msec And \< 60 msec

  14. Moxifloxacin Concentration-related CHFB in QTcF at Day 10

    Time frame · Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    Continuous 12-lead digital ECG recording was performed on Baseline and Day 10. ECG analysts were blinded to the treatment, timepoint and participant. CHFB in QTcF was calculated at each timepoint.

  15. Moxifloxacin Concentration-related CHFB in QTcF at Day 16

    Time frame · Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

    Registry description

    Continuous 12-lead digital ECG recording was performed on Baseline and Day 16. ECG analysts were blinded to the treatment, timepoint and participant. CHFB in QTcF was calculated at each timepoint.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hours (hrs) postdose

Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10

GroupValue (milliseconds (msec))Spread
Group 1: Setmelanotide 3 mg1.97.82
Group 3: Placebo-1.55.25
Primary outcomeMean· Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16

GroupValue (msec)Spread
Group 1: Setmelanotide 7 mg4.56.49
Group 2: Placebo-2.38.24
Secondary and other outcome results(6)
Secondary outcomeMean· Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hours (hrs) postdose

Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10

GroupValue (beats per minute (bpm))Spread
Group 1: Setmelanotide 3 mg2.39.65
Group 2: Moxifloxacin 400 mg-0.37.31
Secondary outcomeMean· Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16

GroupValue (bpm)Spread
Group 1: Setmelanotide 7 mg3.47.41
Group 3: Moxifloxacin 400 mg-0.34.95
Secondary outcomeMean· Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10

GroupValue (msec)Spread
Group 1: Setmelanotide 3 mg1.97.82
Group 2: Moxifloxacin 400 mg1.57.76
Secondary outcomeMean· Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16

GroupValue (msec)Spread
Group 1: Setmelanotide 7 mg4.56.49
Group 3: Moxifloxacin 400 mg-0.88.30
Secondary outcomeMean· Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10

GroupValue (msec)Spread
Group 1: Setmelanotide 3 mg-2.46.12
Group 2: Moxifloxacin 400 mg3.15.18
Secondary outcomeMean· Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose

Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16

GroupValue (msec)Spread
Group 1: Setmelanotide 7 mg-3.57.11
Group 3: Moxifloxacin 400 mg3.411.46

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Group 1: Setmelanotide 2 mgParticipants received once daily setmelanotide 2 mg from Days 1 to 7, via SC injection.0 / 281 / 2825 / 28
Group 1: Setmelanotide 3 mgParticipants received once daily setmelanotide 3 mg from Days 8 to 10, via SC injection.0 / 240 / 2416 / 24
Group 1: Setmelanotide 5 mgParticipants received once daily setmelanotide 5 mg from Days 11 to 13, via SC injection.0 / 230 / 2317 / 23
Group 1: Setmelanotide 7 mgParticipants received once daily setmelanotide 7 mg from Days 14 to 16, via SC injection.0 / 210 / 219 / 21
Group 2: PlaceboParticipants received once daily Placebo from Days 1 to 16, via SC injection and orally on Day 16.0 / 240 / 2418 / 24
Group 2: Moxifloxacin 400mgParticipants received a single oral dose of 400 mg moxifloxacin on Day 10.0 / 230 / 2317 / 23
Group 3: PlaceboParticipants received once daily Placebo from Days 1 to 16, via SC injection and orally on Day 10.0 / 250 / 2515 / 25
Group 3: Moxifloxacin 400mgParticipants received a single oral dose of 400 mg moxifloxacin on Day 16.0 / 250 / 254 / 25

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 50 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
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.

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