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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Oral Placebo (Drug)
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.
干预措施: Setmelanotide (Drug)
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.
干预措施: Oral Placebo (Drug)
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.
干预措施: Moxifloxacin (Drug)
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.
干预措施: Oral Placebo (Drug)
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.
干预措施: SC Placebo (Drug)
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.
干预措施: Moxifloxacin (Drug)
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.
干预措施: SC Placebo (Drug)
结局指标
主要结局
Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10
时间窗: 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
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.
Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16
时间窗: 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
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.
次要结局
- Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16(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 10(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(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 16(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 QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10(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 QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16(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 Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10(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 QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16(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)
- Number of Participants With at Least One Treatment-Emergent Abnormal Value in PR Intervals After Administration of SC Setmelanotide(Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg))
- Number of Participants With at Least One Treatment-Emergent Abnormal Value in QRS Intervals After Administration of SC Setmelanotide(Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg))
- Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide(Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg))
- Number of Participants With at Least One Treatment-Emergent Abnormal Finding in T-wave Morphology and U-wave Presence After Administration of SC Setmelanotide(Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg))
- Moxifloxacin Concentration-related CHFB in QTcF at Day 10(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)
- Moxifloxacin Concentration-related CHFB in QTcF at Day 16(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)
- Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide(Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg))