A Study to Evaluate the Effect of JNJ-53718678 on the Cardiac Repolarization Interval in Healthy Adult Participants

Sponsor:

Collaborators:

Information provided by (Responsible Party):

，

Tracking Information

First Submitted Date ^ICMJE

October 3, 2018

First Posted Date ^ICMJE

October 4, 2018

Last Update Posted Date

October 4, 2018

Actual Study Start Date ^ICMJE

October 3, 2018

Estimated Primary Completion Date

September 20, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Part 2: Placebo-Corrected Change from Baseline in QT Interval Corrected for Heart Rate (QTc) for JNJ‑53718678[ Time Frame: 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.

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Part 1: Number of Participants with Adverse Events as a Measure of Safety and Tolerability[ Time Frame: Approximately up to 9 weeks ]
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Part 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability[ Time Frame: Approximately up to 11 weeks ]
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Part 1: Change from Baseline in QTc Interval[ Time Frame: Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose) ]
The QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by electrocardiograms (ECG).
Part 1: Change from Baseline in Heart Rate (HR)[ Time Frame: Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose) ]
The HR will be measured by ECG.
Part 1: Change from Baseline in PR Interval[ Time Frame: Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose) ]
The PR Intervals will be measured by ECG.
Part 1: Change from Baseline in QRS Interval[ Time Frame: Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose) ]
The QRS Intervals will be measured by ECG.
Part 1: Percentage of Participants with T-Wave Morphology Changes from Baseline[ Time Frame: Baseline up to 72 hours postdose ]
Percentage of participants with T-wave morphology (Normal T-wave, Flat T-waves, Notched T-wave (positive), Biphasic, Normal T-wave (negative), Notched T-wave (negative) changes will be noted.
Part 1: Percentage of Participants with U-Wave Presence[ Time Frame: Baseline up to 72 hours postdose ]
Percentage of participants with U-wave presence will be noted.
Part 2: Change from Baseline in QTc Interval[ Time Frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
The QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by ECG.
Part 2: Change from Baseline in HR[ Time Frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
The HR will be measured by ECG.
Part 2: Change from Baseline PR Interval[ Time Frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
The PR Intervals will be measured by ECG.
Part 2: Change from Baseline QRS Interval[ Time Frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
The QRS Intervals will be measured by ECG.
Part 2: Placebo Corrected Change from Baseline in HR[ Time Frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
Placebo-corrected change from baseline in HR will be determined. The mean change from baseline in HR 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 HR, which will be presented.
Part 2: Placebo Corrected Change from Baseline PR Interval[ Time Frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
Placebo-corrected change from baseline in PR interval will be determined. The mean change from baseline in PR interval 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 PR interval, which will be presented.
Part 2: Placebo Corrected Change from Baseline QRS Interval[ Time Frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
Placebo-corrected change from baseline in QRS interval will be determined. The mean change from baseline in QRS interval 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 QRS interval, which will be presented.
Part 2: Number of Participants with Categorical Outliers for QTc Interval[ Time Frame: Baseline up to 24 hours postdose ]
Number of Participants with categorical outliers defined as QTc interval values greater than (>)450 and lesser than or equal to (<=) 480 milliseconds (ms), >480 and <=500 ms, and >500 ms at any time point and change from baseline QTc >30 ms and <=60 ms, and >60 ms will be determined.
Part 2: Number of Participants with Categorical Outliers for HR[ Time Frame: Baseline up to 24 hours postdose ]
Number of Participants with categorical outliers for HR will be determined for abnormality, where HR is abnormally low (<= 45 beats per minute [bpm]) and abnormally high (>= 120 bpm).
Part 2: Number of Participants with Categorical Outliers for PR Interval[ Time Frame: Baseline up to 24 hours postdose ]
Number of Participants with categorical outliers for PR interval will be determined for abnormality, where PR is abnormally high (>= 210 milliseconds [ms]).
Part 2: Number of Participants with Categorical Outliers for QRS Interval[ Time Frame: Baseline up to 24 hours postdose ]
Number of Participants with categorical outliers for QRS interval will be determined for abnormality, where QRS is abnormally low (<= 50 ms) and abnormally high (>=120 ms).
Part 2: Percentage of Participants with T-Wave Morphology Changes from Baseline[ Time Frame: Baseline up to 24 hours postdose ]
Percentage of participants with T-wave morphology (Normal T-wave, Flat T-waves, Notched T-wave (positive), Biphasic, Normal T-wave (negative), Notched T-wave (negative) changes will be noted.
Part 2: Percentage of Participants with U-Wave Presence[ Time Frame: Baseline up to 24 hours postdose ]
Percentage of participants with U-wave presence will be noted.
Part 1: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)[ Time Frame: 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 ]
Cmax is defined as the maximum observed plasma concentration. Cmax will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)[ Time Frame: 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 ]
Tmax is defined as actual sampling time to reach maximum observed plasma concentration. Tmax will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).
Part 1: Plasma concentration at 24 hours post dosing (C24h) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)[ Time Frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24hours postdose ]
C24h is defined as the plasma concentration at 24 hours post dosing. C24h will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).
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)[ Time Frame: 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 ]
AUC(0-last) is defined as the area under the plasma concentration-time curve from time 0 to the time of the last measurable (non-below quantification level [non-BQL]) plasma concentration calculated by linear-linear trapezoidal summation. AUC [0-last] will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).
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)[ Time Frame: 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 ]
AUC (0-infinity) is defined as the area under the plasma concentration vs. time curve from time 0 to infinite time, calculated as AUC (0-last) + Clast/ lambda (z), where Clast is the last observed measurable (non- BQL) plasma concentration. AUC (0-infinity) will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).
Part 1: Apparent Elimination Half-Life (T1/2) of JNJ- 53718678 and its Metabolites (M5, M12, M19, and M37)[ Time Frame: 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 ]
T1/2 is defined as apparent terminal elimination half-life and is calculated as 0.693/lambda(z) and will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).
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)[ Time Frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
AUC (0-24) is defined as the area under the plasma concentration-time curve from time 0 to 24 hours. AUC (0-24) will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).
Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)[ Time Frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
Cmax is defined as the maximum observed plasma concentration. Cmax will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).
Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)[ Time Frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
Tmax is defined as actual sampling time to reach maximum observed plasma concentration. Tmax will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).
Part 2: Area Under the Plasma Concentration-time Curve from Time 0 to 24 hours (AUC [0-24]) of JNJ-53718678[ Time Frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose ]
AUC (0-24) is defined as the area under the plasma concentration-time curve from time 0 to 24 hours. AUC (0-24) will be assessed for JNJ-53718678 and its metabolites (M5, M12, M19, and M37).

Descriptive Information

Brief Title ^ICMJE

A Study to Evaluate the Effect of JNJ-53718678 on the Cardiac Repolarization Interval in Healthy Adult Participants

Official Title ^ICMJE

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

Brief Summary

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).

Detailed Description

Study Type ^ICMJE

Interventional

Study Phase

Phase 1

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: JNJ-53718678, 2000 mg
Participants will be administered JNJ-53718678, 2000 mg as oral suspension in Part 1 (Panel 1).
Drug: JNJ-53718678, 3000 mg
Participants will be administered JNJ 53718678, 3000 mg (or a lower dose if deemed appropriate from safety and PK perspective) as oral suspension in Part 1 (Panel 2) and Part 2 of study.
Drug: JNJ-53718678, 500 mg
Participants will be administered JNJ-53718678, 500 mg as oral suspension in Part 2.
Drug: JNJ-53718678 Placebo
Participants will be administered JNJ-53718678 matching placebo in Part 1 and 2.
Drug: Moxifloxacin 400 mg
Participants will be administered moxifloxacin 400 mg as capsule in Part 2.
Drug: Moxifloxacin Placebo
Participants will be administered moxifloxacin matching placebo in Part 2.

Study Arms

Experimental: 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.
Experimental: 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. However, based on review of safety, tolerability, and PK data obtained in Panel 1 this dose may be lowered.
Experimental: 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, 3000 mg (based on review of safety, tolerability, and PK data obtained in Part 1 this dose may be lowered) 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.
Experimental: 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.
Experimental: 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.
Experimental: 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.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

March 20, 2020

Estimated Primary Completion Date

September 20, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria: - Participants must have a Body mass index (BMI) between 18 and 30 kilogram per square meter (kg/m^2) (inclusive), and body weight 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) Exclusion Criteria: - 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

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Belgium

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

Janssen Research & Development, LLC

Collaborators ^ICMJE

Investigators ^ICMJE

Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

PRS Account

Verification Date

September 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

请使用微信扫码报名