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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03696459
• Other study ID #: CR108519
• Secondary ID: 2018-000878-3053
• Status: Completed
• Phase: Phase 1
• Start date: October 2, 2018
• Est. completion date: December 13, 2019

Study information

• Verified date: February 2020
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 13, 2019
• Est. primary completion date: December 13, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 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)

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-53718678, 2000 mg
Participants will be administered JNJ-53718678, 2000 mg as oral suspension in Part 1 (Panel 1).
• JNJ-53718678, 3000 mg
Participants will be administered JNJ- 53718678, 3000 mg as oral suspension in Part 1 (Panel 2).
• JNJ-53718678, 4500 mg or Dose to be decided
Participants will be administered JNJ-53718678, 4500 mg as oral suspension in Part 1 (Panel 3). If this dose is considered safe and tolerable and if pharmacokinetic data require further dose escalation, then participants will receive JNJ-53718678 (Dose to be decided) in Part 1 (Panel 4). This dose (either from Panel 3 or Panel 4 ) will be used in Part 2 (Dose may be lower/higher based on review of safety, tolerability, and PK data obtained in Part 1).
• JNJ-53718678 500 mg
Participants will be administered JNJ-53718678, 500 mg as oral suspension in Part 2.
• JNJ-53718678 Placebo
Participants will be administered JNJ-53718678 matching placebo in Part 1 and 2.
• Moxifloxacin 400 mg
Participants will be administered moxifloxacin 400 mg as capsule in Part 2.
• Moxifloxacin Placebo
Participants will be administered moxifloxacin matching placebo in Part 2.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 2: Placebo-Corrected Change from Baseline in QT Interval Corrected for Heart Rate (QTc) for JNJ-53718678	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.	Baseline and Day 1
Secondary	Part 1: Number of Participants with Adverse Events as a Measure of Safety and Tolerability	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.	Approximately up to 9 weeks
Secondary	Part 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability	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.	Approximately up to 12 weeks
Secondary	Part 1: Change from Baseline in QTc Interval	The QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by electrocardiograms (ECG).	Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)
Secondary	Part 1: Change from Baseline in Heart Rate (HR)	The HR will be measured by ECG.	Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)
Secondary	Part 1: Change from Baseline in PR Interval	The PR Intervals will be measured by ECG.	Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)
Secondary	Part 1: Change from Baseline in QRS Interval	The QRS Intervals will be measured by ECG.	Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)
Secondary	Part 1: Percentage of Participants with T-Wave Morphology Changes from Baseline	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.	Baseline up to 72 hours postdose
Secondary	Part 1: Percentage of Participants with U-Wave Presence	Percentage of participants with U-wave presence will be noted.	Baseline up to 72 hours postdose
Secondary	Part 2: Change from Baseline in QTc Interval	The QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by ECG.	Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Secondary	Part 2: Change from Baseline in HR	The HR will be measured by ECG.	Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Secondary	Part 2: Change from Baseline PR Interval	The PR Intervals will be measured by ECG.	Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Secondary	Part 2: Change from Baseline QRS Interval	The QRS Intervals will be measured by ECG.	Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Secondary	Part 2: Placebo Corrected Change from Baseline in HR	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.	Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Secondary	Part 2: Placebo Corrected Change from Baseline PR Interval	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.	Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Secondary	Part 2: Placebo Corrected Change from Baseline QRS Interval	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.	Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Secondary	Part 2: Number of Participants with Categorical Outliers for QTc Interval	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.	Baseline up to 24 hours postdose
Secondary	Part 2: Number of Participants with Categorical Outliers for HR	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).	Baseline up to 24 hours postdose
Secondary	Part 2: Number of Participants with Categorical Outliers for PR Interval	Number of Participants with categorical outliers for PR interval will be determined for abnormality, where PR is abnormally high (>= 210 milliseconds [ms]).	Baseline up to 24 hours postdose
Secondary	Part 2: Number of Participants with Categorical Outliers for QRS Interval	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).	Baseline up to 24 hours postdose
Secondary	Part 2: Percentage of Participants with T-Wave Morphology Changes from Baseline	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.	Baseline up to 24 hours postdose
Secondary	Part 2: Percentage of Participants with U-Wave Presence	Percentage of participants with U-wave presence will be noted.	Baseline up to 24 hours postdose
Secondary	Part 1: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)	Cmax is defined as the maximum observed plasma concentration. Cmax will be assessed for 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
Secondary	Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)	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).	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
Secondary	Part 1: Plasma concentration at 24 hours post dosing (C24h) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)	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).	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24hours postdose
Secondary	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)	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).	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Secondary	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)	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).	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
Secondary	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)	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).	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
Secondary	Part 1: Apparent Elimination Half-Life (T1/2) of JNJ- 53718678 and its Metabolites (M5, M12, M19, and M37)	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).	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
Secondary	Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)	Cmax is defined as the maximum observed plasma concentration. Cmax will be assessed for 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
Secondary	Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)	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).	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Secondary	Part 2: Area Under the Plasma Concentration-time Curve from Time 0 to 24 hours (AUC [0-24]) of JNJ-53718678	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).	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose

External Links

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