A Double-blind, Randomized, Placebo-controlled, 4-Period Cross-over Study to Evaluate the Effect of JNJ-53718678 on the Cardiac Repolarization Interval in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Part 2: Placebo-Corrected Change from Baseline in QT Interval Corrected for Heart Rate (QTc) for JNJ-53718678
研究概览
简要总结
The purpose of this study is to assess the effect of JNJ-53718678 on QT interval corrected for heart rate (QTc) changes using exposure response analysis in healthy adult participants (Part 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must have a Body mass index (BMI) between 18 and 30 kilogram per square meter (kg/m^2) (inclusive), and body weight not less than (<) 50 kg at screening
- •Participants must have a blood pressure between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic at screening
- •Participants must have a 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function at screening, including: a) Normal sinus rhythm (heart rate (HR) between 45 and 100 beats per minute (bpm), inclusive); b) QT interval corrected for HR according to Fridericia's formula (QTcF) between 350 milliseconds (ms) and 430 ms for male participants, and between 350 ms and 450 ms for female participants (inclusive); c) QRS interval of ECG <110 ms; d) PR interval of the ECG less-than or equal to (<=) 200 ms; e) Morphology consistent with healthy cardiac conduction and function
- •A female participant must be of non-childbearing potential, defined as: a) Postmenopausal or b) Permanently sterile
- •A female participant must have a negative serum beta-human chorionic gonadotropin (b-hCG) pregnancy test at screening and a negative urine pregnancy test (except if postmenopausal) on Day -1 (or Day -2 in the first treatment period in Part 2)
排除标准
- •Participants has a history of current clinically significant medical illness or certain laboratory abnormalities at screening
- •Participant has a history of hepatitis A virus immunoglobulin M (IgM) antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody positive, or other clinically active liver disease, or tests positive for hepatitis A virus IgM antibody, HBsAg or HCV antibody at screening
- •Participants with unusual T wave morphology (such as bifid T wave) likely to interfere with QTc measurements
- •Participants with a past history of heart arrhythmias or with a history of risk factors for Torsade de Pointes syndrome (for example, hypokalemia or family history of short/long QT syndrome, or sudden unexplained death at a young age [<=40 years], drowning or sudden infant death in a first degree relative [that is, sibling, offspring, or biological parent])
- •Participants with any skin condition likely to interfere with ECG electrode placement or adhesion
研究组 & 干预措施
Part 1 (Dose Escalation): Panel 1
Participants will receive single oral dose of JNJ-53718678, 2000 milligram (mg) suspension or matching placebo on Day 1, under fasted conditions.
干预措施: JNJ-53718678, 2000 mg (Drug)
Part 1 (Dose Escalation): Panel 1
Participants will receive single oral dose of JNJ-53718678, 2000 milligram (mg) suspension or matching placebo on Day 1, under fasted conditions.
干预措施: JNJ-53718678 Placebo (Drug)
Part 1 (Dose Escalation): Panel 2
Participants will receive single oral dose of JNJ-53718678, of maximum 3000 mg suspension or matching placebo on Day 1, under fasted conditions.
干预措施: JNJ-53718678, 3000 mg (Drug)
Part 1 (Dose Escalation): Panel 2
Participants will receive single oral dose of JNJ-53718678, of maximum 3000 mg suspension or matching placebo on Day 1, under fasted conditions.
干预措施: JNJ-53718678 Placebo (Drug)
Part 1 (Dose escalation): Panel 3
Participants will receive single oral dose of JNJ-53718678 4500 mg suspension (this dose may be used in Part 2, Treatment F) or matching placebo on Day 1, under fasted condition.
干预措施: JNJ-53718678, 4500 mg or Dose to be decided (Drug)
Part 1 (Dose escalation): Panel 3
Participants will receive single oral dose of JNJ-53718678 4500 mg suspension (this dose may be used in Part 2, Treatment F) or matching placebo on Day 1, under fasted condition.
干预措施: JNJ-53718678 Placebo (Drug)
Part 1 (Dose Escalation): Panel 4 (Optional)
Participants will receive single oral dose of JNJ-53718678 (dose to be decided [this dose may be used in Part 2, Treatment F]) suspension or matching placebo on Day 1, under fasted condition, if 4500 mg dose in Panel 3 is considered safe and tolerable and if pharmacokinetic data require further dose escalation to reach the target exposure.
干预措施: JNJ-53718678, 4500 mg or Dose to be decided (Drug)
Part 1 (Dose Escalation): Panel 4 (Optional)
Participants will receive single oral dose of JNJ-53718678 (dose to be decided [this dose may be used in Part 2, Treatment F]) suspension or matching placebo on Day 1, under fasted condition, if 4500 mg dose in Panel 3 is considered safe and tolerable and if pharmacokinetic data require further dose escalation to reach the target exposure.
干预措施: JNJ-53718678 Placebo (Drug)
Part 2 Group 1: Treatment Sequence EHFG
Participants will receive single oral dose of JNJ-53718678, 500 mg suspension with single oral dose of moxifloxacin placebo and JNJ 53718678 placebo (Treatment E) in Period 1, then participants will receive single oral dose of moxifloxacin 400 mg with single oral dose of JNJ-53718678 placebo (Treatment H) in Period 2 then will receive single oral dose of JNJ-53718678, 4500 mg (dose will be based on review of safety, tolerability, and PK data obtained in Part 1 [either from Panel 3 or 4], this dose may be lower/higher) suspension with single oral dose of moxifloxacin placebo (Treatment F) in Period 3 followed by single oral dose of JNJ-53718678 placebo with single oral dose of moxifloxacin placebo (Treatment G) in Period 4, on Day 1 of each treatment period. There will be a washout period of at least 7 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-53718678, 4500 mg or Dose to be decided (Drug)
Part 2 Group 1: Treatment Sequence EHFG
Participants will receive single oral dose of JNJ-53718678, 500 mg suspension with single oral dose of moxifloxacin placebo and JNJ 53718678 placebo (Treatment E) in Period 1, then participants will receive single oral dose of moxifloxacin 400 mg with single oral dose of JNJ-53718678 placebo (Treatment H) in Period 2 then will receive single oral dose of JNJ-53718678, 4500 mg (dose will be based on review of safety, tolerability, and PK data obtained in Part 1 [either from Panel 3 or 4], this dose may be lower/higher) suspension with single oral dose of moxifloxacin placebo (Treatment F) in Period 3 followed by single oral dose of JNJ-53718678 placebo with single oral dose of moxifloxacin placebo (Treatment G) in Period 4, on Day 1 of each treatment period. There will be a washout period of at least 7 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-53718678 500 mg (Drug)
Part 2 Group 1: Treatment Sequence EHFG
Participants will receive single oral dose of JNJ-53718678, 500 mg suspension with single oral dose of moxifloxacin placebo and JNJ 53718678 placebo (Treatment E) in Period 1, then participants will receive single oral dose of moxifloxacin 400 mg with single oral dose of JNJ-53718678 placebo (Treatment H) in Period 2 then will receive single oral dose of JNJ-53718678, 4500 mg (dose will be based on review of safety, tolerability, and PK data obtained in Part 1 [either from Panel 3 or 4], this dose may be lower/higher) suspension with single oral dose of moxifloxacin placebo (Treatment F) in Period 3 followed by single oral dose of JNJ-53718678 placebo with single oral dose of moxifloxacin placebo (Treatment G) in Period 4, on Day 1 of each treatment period. There will be a washout period of at least 7 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-53718678 Placebo (Drug)
Part 2 Group 1: Treatment Sequence EHFG
Participants will receive single oral dose of JNJ-53718678, 500 mg suspension with single oral dose of moxifloxacin placebo and JNJ 53718678 placebo (Treatment E) in Period 1, then participants will receive single oral dose of moxifloxacin 400 mg with single oral dose of JNJ-53718678 placebo (Treatment H) in Period 2 then will receive single oral dose of JNJ-53718678, 4500 mg (dose will be based on review of safety, tolerability, and PK data obtained in Part 1 [either from Panel 3 or 4], this dose may be lower/higher) suspension with single oral dose of moxifloxacin placebo (Treatment F) in Period 3 followed by single oral dose of JNJ-53718678 placebo with single oral dose of moxifloxacin placebo (Treatment G) in Period 4, on Day 1 of each treatment period. There will be a washout period of at least 7 days between study drug intake in subsequent treatment periods.
干预措施: Moxifloxacin 400 mg (Drug)
Part 2 Group 1: Treatment Sequence EHFG
Participants will receive single oral dose of JNJ-53718678, 500 mg suspension with single oral dose of moxifloxacin placebo and JNJ 53718678 placebo (Treatment E) in Period 1, then participants will receive single oral dose of moxifloxacin 400 mg with single oral dose of JNJ-53718678 placebo (Treatment H) in Period 2 then will receive single oral dose of JNJ-53718678, 4500 mg (dose will be based on review of safety, tolerability, and PK data obtained in Part 1 [either from Panel 3 or 4], this dose may be lower/higher) suspension with single oral dose of moxifloxacin placebo (Treatment F) in Period 3 followed by single oral dose of JNJ-53718678 placebo with single oral dose of moxifloxacin placebo (Treatment G) in Period 4, on Day 1 of each treatment period. There will be a washout period of at least 7 days between study drug intake in subsequent treatment periods.
干预措施: Moxifloxacin Placebo (Drug)
Part 2 Group 2: Treatment Sequence FEGH
Participants will receive Treatment F in Period 1, then Treatment E in Period 2, then Treatment G in Period 3 followed by Treatment H in Period 4 on Day 1 of each treatment period.
干预措施: JNJ-53718678, 4500 mg or Dose to be decided (Drug)
Part 2 Group 2: Treatment Sequence FEGH
Participants will receive Treatment F in Period 1, then Treatment E in Period 2, then Treatment G in Period 3 followed by Treatment H in Period 4 on Day 1 of each treatment period.
干预措施: JNJ-53718678 500 mg (Drug)
Part 2 Group 2: Treatment Sequence FEGH
Participants will receive Treatment F in Period 1, then Treatment E in Period 2, then Treatment G in Period 3 followed by Treatment H in Period 4 on Day 1 of each treatment period.
干预措施: JNJ-53718678 Placebo (Drug)
Part 2 Group 2: Treatment Sequence FEGH
Participants will receive Treatment F in Period 1, then Treatment E in Period 2, then Treatment G in Period 3 followed by Treatment H in Period 4 on Day 1 of each treatment period.
干预措施: Moxifloxacin 400 mg (Drug)
Part 2 Group 2: Treatment Sequence FEGH
Participants will receive Treatment F in Period 1, then Treatment E in Period 2, then Treatment G in Period 3 followed by Treatment H in Period 4 on Day 1 of each treatment period.
干预措施: Moxifloxacin Placebo (Drug)
Part 2 Group 3: Treatment Sequence GFHE
Participants will receive Treatment G in Period 1, then Treatment F in Period 2, then Treatment H in Period 3 followed by Treatment E in Period 4 on Day 1 of each treatment period.
干预措施: JNJ-53718678, 4500 mg or Dose to be decided (Drug)
Part 2 Group 3: Treatment Sequence GFHE
Participants will receive Treatment G in Period 1, then Treatment F in Period 2, then Treatment H in Period 3 followed by Treatment E in Period 4 on Day 1 of each treatment period.
干预措施: JNJ-53718678 500 mg (Drug)
Part 2 Group 3: Treatment Sequence GFHE
Participants will receive Treatment G in Period 1, then Treatment F in Period 2, then Treatment H in Period 3 followed by Treatment E in Period 4 on Day 1 of each treatment period.
干预措施: JNJ-53718678 Placebo (Drug)
Part 2 Group 3: Treatment Sequence GFHE
Participants will receive Treatment G in Period 1, then Treatment F in Period 2, then Treatment H in Period 3 followed by Treatment E in Period 4 on Day 1 of each treatment period.
干预措施: Moxifloxacin 400 mg (Drug)
Part 2 Group 3: Treatment Sequence GFHE
Participants will receive Treatment G in Period 1, then Treatment F in Period 2, then Treatment H in Period 3 followed by Treatment E in Period 4 on Day 1 of each treatment period.
干预措施: Moxifloxacin Placebo (Drug)
Part 2 Group 4: Treatment Sequence HGEF
Participants will receive Treatment H in Period 1, then Treatment G in Period 2, then Treatment E in Period 3 followed by Treatment F in Period 4 on Day 1 of each treatment period.
干预措施: JNJ-53718678, 4500 mg or Dose to be decided (Drug)
Part 2 Group 4: Treatment Sequence HGEF
Participants will receive Treatment H in Period 1, then Treatment G in Period 2, then Treatment E in Period 3 followed by Treatment F in Period 4 on Day 1 of each treatment period.
干预措施: JNJ-53718678 500 mg (Drug)
Part 2 Group 4: Treatment Sequence HGEF
Participants will receive Treatment H in Period 1, then Treatment G in Period 2, then Treatment E in Period 3 followed by Treatment F in Period 4 on Day 1 of each treatment period.
干预措施: JNJ-53718678 Placebo (Drug)
Part 2 Group 4: Treatment Sequence HGEF
Participants will receive Treatment H in Period 1, then Treatment G in Period 2, then Treatment E in Period 3 followed by Treatment F in Period 4 on Day 1 of each treatment period.
干预措施: Moxifloxacin 400 mg (Drug)
Part 2 Group 4: Treatment Sequence HGEF
Participants will receive Treatment H in Period 1, then Treatment G in Period 2, then Treatment E in Period 3 followed by Treatment F in Period 4 on Day 1 of each treatment period.
干预措施: Moxifloxacin Placebo (Drug)
结局指标
主要结局
Part 2: Placebo-Corrected Change from Baseline in QT Interval Corrected for Heart Rate (QTc) for JNJ-53718678
时间窗: Baseline and Day 1
Placebo-corrected change from baseline in QT interval corrected for heart rate (QTc) will be determined. The mean change from baseline in QTc in placebo treatment will be subtracted from the mean change from baseline in JNJ-53718678 treatment at the same time point to generate placebo-corrected change from baseline in QTc, which will be presented.
次要结局
- Part 1: Change from Baseline in Heart Rate (HR)(Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose))
- Part 1: Change from Baseline in PR Interval(Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose))
- Part 1: Change from Baseline in QRS Interval(Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose))
- Part 1: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- Part 1: Plasma concentration at 24 hours post dosing (C24h) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24hours postdose)
- Part 1: Area Under the Plasma Concentration-time Curve from Time 0 to 24 hours (AUC [0-24]) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 1: Area Under the Plasma Concentration-time Curve from Time Zero to the Time of Last Measurable Concentration (AUC [0-last]) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- Part 1: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- Part 1: Percentage of Participants with T-Wave Morphology Changes from Baseline(Baseline up to 72 hours postdose)
- Part 1: Number of Participants with Adverse Events as a Measure of Safety and Tolerability(Approximately up to 9 weeks)
- Part 2: Placebo Corrected Change from Baseline PR Interval(Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Number of Participants with Categorical Outliers for QTc Interval(Baseline up to 24 hours postdose)
- Part 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability(Approximately up to 12 weeks)
- Part 1: Change from Baseline in QTc Interval(Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose))
- Part 2: Placebo Corrected Change from Baseline in HR(Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 1: Percentage of Participants with U-Wave Presence(Baseline up to 72 hours postdose)
- Part 2: Change from Baseline in QTc Interval(Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Change from Baseline PR Interval(Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Change from Baseline QRS Interval(Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Change from Baseline in HR(Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Placebo Corrected Change from Baseline QRS Interval(Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Number of Participants with Categorical Outliers for HR(Baseline up to 24 hours postdose)
- Part 2: Number of Participants with Categorical Outliers for PR Interval(Baseline up to 24 hours postdose)
- Part 2: Number of Participants with Categorical Outliers for QRS Interval(Baseline up to 24 hours postdose)
- Part 2: Percentage of Participants with T-Wave Morphology Changes from Baseline(Baseline up to 24 hours postdose)
- Part 2: Percentage of Participants with U-Wave Presence(Baseline up to 24 hours postdose)
- Part 1: Apparent Elimination Half-Life (T1/2) of JNJ- 53718678 and its Metabolites (M5, M12, M19, and M37)(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)
- Part 2: Area Under the Plasma Concentration-time Curve from Time 0 to 24 hours (AUC [0-24]) of JNJ-53718678(Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose)