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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05046132
• Other study ID #: RM-493-032
• Secondary ID: 263791
• Status: Completed
• Phase: Phase 4
• Start date: August 5, 2021
• Est. completion date: April 7, 2022

Study information

• Verified date: April 2024
• Source: Rhythm Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: April 7, 2022
• Est. primary completion date: April 7, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Setmelanotide
Administered once daily via SC injection.
• Moxifloxacin
Moxifloxacin capsules via oral administration.
• Oral Placebo
Placebo capsules via oral administration.
• SC Placebo
Placebo via SC injection.

Locations

Country	Name	City	State
United States	Parexel Early Phase Clinical Unit (Los Angeles)	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Rhythm Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10	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.	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
Primary	Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16	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.	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
Secondary	Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10	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.	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
Secondary	Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16	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.	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
Secondary	Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10	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.	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
Secondary	Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16	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.	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
Secondary	Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10	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.	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
Secondary	Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16	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.	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
Secondary	Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10	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.	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
Secondary	Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16	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.	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
Secondary	Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide	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	Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Secondary	Number of Participants With at Least One Treatment-Emergent Abnormal Value in PR Intervals After Administration of SC Setmelanotide	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	Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Secondary	Number of Participants With at Least One Treatment-Emergent Abnormal Value in QRS Intervals After Administration of SC Setmelanotide	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	Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Secondary	Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide	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	Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Secondary	Number of Participants With at Least One Treatment-Emergent Abnormal Finding in T-wave Morphology and U-wave Presence After Administration of SC Setmelanotide	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	Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Secondary	Moxifloxacin Concentration-related CHFB in QTcF at Day 10	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.	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
Secondary	Moxifloxacin Concentration-related CHFB in QTcF at Day 16	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.	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