Clinical trial NCT03696459: A Study to Evaluate the Effect of JNJ-53718678 on the Cardiac Repolarization Interval in Healthy Adult Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-10-04
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Part 2: Placebo-Corrected Change from Baseline in QT Interval Corrected for Heart Rate (QTc) for JNJ-53718678
timeFrame: Baseline and Day 1
Secondary outcomes:
measure: Part 1: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Approximately up to 9 weeks
measure: Part 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Approximately up to 12 weeks
measure: Part 1: Change from Baseline in QTc Interval
timeFrame: Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)
measure: Part 1: Change from Baseline in Heart Rate (HR)
timeFrame: Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)
measure: Part 1: Change from Baseline in PR Interval
timeFrame: Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)
measure: Part 1: Change from Baseline in QRS Interval
timeFrame: Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)
measure: Part 1: Percentage of Participants with T-Wave Morphology Changes from Baseline
timeFrame: Baseline up to 72 hours postdose
measure: Part 1: Percentage of Participants with U-Wave Presence
timeFrame: Baseline up to 72 hours postdose
measure: Part 2: Change from Baseline in QTc Interval
timeFrame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: Part 2: Change from Baseline in HR
timeFrame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: Part 2: Change from Baseline PR Interval
timeFrame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: Part 2: Change from Baseline QRS Interval
timeFrame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: Part 2: Placebo Corrected Change from Baseline in HR
timeFrame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: Part 2: Placebo Corrected Change from Baseline PR Interval
timeFrame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: Part 2: Placebo Corrected Change from Baseline QRS Interval
timeFrame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: Part 2: Number of Participants with Categorical Outliers for QTc Interval
timeFrame: Baseline up to 24 hours postdose
measure: Part 2: Number of Participants with Categorical Outliers for HR
timeFrame: Baseline up to 24 hours postdose
measure: Part 2: Number of Participants with Categorical Outliers for PR Interval
timeFrame: Baseline up to 24 hours postdose
measure: Part 2: Number of Participants with Categorical Outliers for QRS Interval
timeFrame: Baseline up to 24 hours postdose
measure: Part 2: Percentage of Participants with T-Wave Morphology Changes from Baseline
timeFrame: Baseline up to 24 hours postdose
measure: Part 2: Percentage of Participants with U-Wave Presence
timeFrame: Baseline up to 24 hours postdose
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)
timeFrame: 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
measure: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)
timeFrame: 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
measure: Part 1: Plasma concentration at 24 hours post dosing (C24h) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24hours postdose
measure: 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)
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Part 1: Apparent Elimination Half-Life (T1/2) of JNJ- 53718678 and its Metabolites (M5, M12, M19, and M37)
timeFrame: 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
measure: Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-53718678 and its Metabolites (M5, M12, M19, and M37)
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
measure: Part 2: Area Under the Plasma Concentration-time Curve from Time 0 to 24 hours (AUC [0-24]) of JNJ-53718678
timeFrame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: