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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: JNJ-53718678, 2000 mg; Drug: JNJ-53718678 Placebo; Drug: Moxifloxacin 400 mg; Drug: JNJ-53718678 500 mg; Drug: JNJ-53718678, 4500 mg or Dose to be decided; Drug: JNJ-53718678, 3000 mg; Drug: Moxifloxacin Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03696459

2018-000878-30 (EudraCT Number)

53718678RSV1009 (Other Identifier)

CR108519

Details and patient eligibility

About

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).

Enrollment: 52 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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52 participants in 8 patient groups

Part 1 (Dose Escalation): Panel 1

Experimental group

Description:

Participants will receive single oral dose of JNJ-53718678, 2000 milligram (mg) suspension or matching placebo on Day 1, under fasted conditions.

Treatment:

Drug: JNJ-53718678, 2000 mg

Drug: JNJ-53718678 Placebo

Part 1 (Dose Escalation): Panel 2

Experimental group

Description:

Participants will receive single oral dose of JNJ-53718678, of maximum 3000 mg suspension or matching placebo on Day 1, under fasted conditions.

Treatment:

Drug: JNJ-53718678, 3000 mg

Drug: JNJ-53718678 Placebo

Part 1 (Dose escalation): Panel 3

Experimental group

Description:

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.

Treatment:

Drug: JNJ-53718678, 4500 mg or Dose to be decided

Drug: JNJ-53718678 Placebo

Part 1 (Dose Escalation): Panel 4 (Optional)

Experimental group

Description:

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.

Treatment:

Drug: JNJ-53718678, 4500 mg or Dose to be decided

Drug: JNJ-53718678 Placebo

Part 2 Group 1: Treatment Sequence EHFG

Experimental group

Description:

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.

Treatment:

Drug: Moxifloxacin 400 mg

Drug: JNJ-53718678 500 mg

Drug: Moxifloxacin Placebo

Drug: JNJ-53718678, 4500 mg or Dose to be decided

Drug: JNJ-53718678 Placebo

Part 2 Group 2: Treatment Sequence FEGH

Experimental group

Description:

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.

Treatment:

Drug: Moxifloxacin 400 mg

Drug: JNJ-53718678 500 mg

Drug: Moxifloxacin Placebo

Drug: JNJ-53718678, 4500 mg or Dose to be decided

Drug: JNJ-53718678 Placebo

Part 2 Group 3: Treatment Sequence GFHE

Experimental group

Description:

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.

Treatment:

Drug: Moxifloxacin 400 mg

Drug: JNJ-53718678 500 mg

Drug: Moxifloxacin Placebo

Drug: JNJ-53718678, 4500 mg or Dose to be decided

Drug: JNJ-53718678 Placebo

Part 2 Group 4: Treatment Sequence HGEF

Experimental group

Description:

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.

Treatment:

Drug: Moxifloxacin 400 mg

Drug: JNJ-53718678 500 mg

Drug: Moxifloxacin Placebo

Drug: JNJ-53718678, 4500 mg or Dose to be decided

Drug: JNJ-53718678 Placebo