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Completed

NCT Number: NCT03696459

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

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).

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Key information

Conditions

Healthy

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

JNJ-53718678, 2000 mg

Drug

Participants will be administered JNJ-53718678, 2000 mg as oral suspension in Part 1 (Panel 1).

JNJ-53718678, 3000 mg

Drug

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

Drug

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

Drug

Participants will be administered JNJ-53718678, 500 mg as oral suspension in Part 2.

JNJ-53718678 Placebo

Drug

Participants will be administered JNJ-53718678 matching placebo in Part 1 and 2.

Moxifloxacin 400 mg

Drug

Participants will be administered moxifloxacin 400 mg as capsule in Part 2.

Moxifloxacin Placebo

Drug

Participants will be administered moxifloxacin matching placebo in Part 2.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. Part 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    Time frame: Approximately up to 12 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.

  3. 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).

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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).

  18. 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]).

  19. 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).

  20. 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.

  21. 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.

  22. 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).

  23. 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).

  24. 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).

  25. 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).

  26. 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).

  27. 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).

  28. 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).

  29. 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).

  30. 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).

  31. 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).

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Oct 4, 2018
Registry last updated
Feb 18, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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