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

NCT ID: NCT03696459

Last Updated: 2020-02-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-02
• Study Completion Date: 2019-12-13

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).

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

JNJ-53718678, 2000 mg

Intervention Type: DRUG

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

JNJ-53718678 Placebo

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

JNJ-53718678, 3000 mg

Intervention Type: DRUG

Participants will be administered JNJ- 53718678, 3000 mg as oral suspension in Part 1 (Panel 2).

JNJ-53718678 Placebo

Intervention Type: DRUG

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

Part 1 (Dose escalation): Panel 3

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.

Group Type: EXPERIMENTAL

JNJ-53718678, 4500 mg or Dose to be decided

Intervention Type: 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 Placebo

Intervention Type: DRUG

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

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

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.

Group Type: EXPERIMENTAL

JNJ-53718678, 4500 mg or Dose to be decided

Intervention Type: 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 Placebo

Intervention Type: DRUG

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

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, 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.

Group Type: EXPERIMENTAL

JNJ-53718678, 4500 mg or Dose to be decided

Intervention Type: 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

Intervention Type: DRUG

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

JNJ-53718678 Placebo

Intervention Type: DRUG

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

Moxifloxacin 400 mg

Intervention Type: DRUG

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

Moxifloxacin Placebo

Intervention Type: DRUG

Participants will be administered moxifloxacin matching placebo in Part 2.

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.

Group Type: EXPERIMENTAL

JNJ-53718678, 4500 mg or Dose to be decided

Intervention Type: 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

Intervention Type: DRUG

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

JNJ-53718678 Placebo

Intervention Type: DRUG

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

Moxifloxacin 400 mg

Intervention Type: DRUG

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

Moxifloxacin Placebo

Intervention Type: DRUG

Participants will be administered moxifloxacin matching placebo in Part 2.

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.

Group Type: EXPERIMENTAL

JNJ-53718678, 4500 mg or Dose to be decided

Intervention Type: 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

Intervention Type: DRUG

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

JNJ-53718678 Placebo

Intervention Type: DRUG

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

Moxifloxacin 400 mg

Intervention Type: DRUG

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

Moxifloxacin Placebo

Intervention Type: DRUG

Participants will be administered moxifloxacin matching placebo in Part 2.

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.

Group Type: EXPERIMENTAL

JNJ-53718678, 4500 mg or Dose to be decided

Intervention Type: 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

Intervention Type: DRUG

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

JNJ-53718678 Placebo

Intervention Type: DRUG

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

Moxifloxacin 400 mg

Intervention Type: DRUG

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

Moxifloxacin Placebo

Intervention Type: DRUG

Participants will be administered moxifloxacin matching placebo in Part 2.

Interventions

JNJ-53718678, 2000 mg

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

Intervention Type: DRUG

JNJ-53718678, 3000 mg

Participants will be administered JNJ- 53718678, 3000 mg as oral suspension in Part 1 (Panel 2).

Intervention Type: DRUG

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).

Intervention Type: DRUG

JNJ-53718678 500 mg

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

Intervention Type: DRUG

JNJ-53718678 Placebo

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

Intervention Type: DRUG

Moxifloxacin 400 mg

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

Intervention Type: DRUG

Moxifloxacin Placebo

Participants will be administered moxifloxacin matching placebo in Part 2.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Clinical Pharmacology Unit

Merksem, , Belgium

Countries

Belgium

Other Identifiers

2018-000878-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

53718678RSV1009

Identifier Type: OTHER

Identifier Source: secondary_id

CR108519

Identifier Type: -

Identifier Source: org_study_id