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

NCT03696459 | Completed Phase 1 FDA Drug

• 3 other identifiers: CR1085192018-000878-3053718678RSV1009
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (31)

• Part 1: Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Approximately up to 9 weeks

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

  Approximately up to 12 weeks

• Part 1: Change from Baseline in QTc Interval

  Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)

• Part 1: Change from Baseline in Heart Rate (HR)

  Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)

• Part 1: Change from Baseline in PR Interval

  Baseline, 3, 24, 72 hours and at follow-up (10-14 days postdose)

Study Arms (8)

Part 1 (Dose Escalation): Panel 1

EXPERIMENTAL

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

Drug: JNJ-53718678, 2000 mg; Drug: JNJ-53718678 Placebo

Part 1 (Dose Escalation): Panel 2

EXPERIMENTAL

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

Drug: JNJ-53718678, 3000 mg; Drug: JNJ-53718678 Placebo

Part 1 (Dose escalation): Panel 3

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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.

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

Part 2 Group 1: Treatment Sequence EHFG

EXPERIMENTAL

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.

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

Part 2 Group 2: Treatment Sequence FEGH

EXPERIMENTAL

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.

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

Part 2 Group 3: Treatment Sequence GFHE

EXPERIMENTAL

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.

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

Part 2 Group 4: Treatment Sequence HGEF

EXPERIMENTAL

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.

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

Interventions

JNJ-53718678, 2000 mg DRUG

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

Part 1 (Dose Escalation): Panel 1

JNJ-53718678, 3000 mg DRUG

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

Part 1 (Dose Escalation): 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).

Part 1 (Dose Escalation): Panel 4 (Optional); Part 1 (Dose escalation): Panel 3; Part 2 Group 1: Treatment Sequence EHFG; Part 2 Group 2: Treatment Sequence FEGH; Part 2 Group 3: Treatment Sequence GFHE; Part 2 Group 4: Treatment Sequence HGEF

JNJ-53718678 500 mg DRUG

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

Part 2 Group 1: Treatment Sequence EHFG; Part 2 Group 2: Treatment Sequence FEGH; Part 2 Group 3: Treatment Sequence GFHE; Part 2 Group 4: Treatment Sequence HGEF

JNJ-53718678 Placebo DRUG

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

Part 1 (Dose Escalation): Panel 1; Part 1 (Dose Escalation): Panel 2; Part 1 (Dose Escalation): Panel 4 (Optional); Part 1 (Dose escalation): Panel 3; Part 2 Group 1: Treatment Sequence EHFG; Part 2 Group 2: Treatment Sequence FEGH; Part 2 Group 3: Treatment Sequence GFHE; Part 2 Group 4: Treatment Sequence HGEF

Moxifloxacin 400 mg DRUG

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

Part 2 Group 1: Treatment Sequence EHFG; Part 2 Group 2: Treatment Sequence FEGH; Part 2 Group 3: Treatment Sequence GFHE; Part 2 Group 4: Treatment Sequence HGEF

Moxifloxacin Placebo DRUG

Participants will be administered moxifloxacin matching placebo in Part 2.

Part 2 Group 1: Treatment Sequence EHFG; Part 2 Group 2: Treatment Sequence FEGH; Part 2 Group 3: Treatment Sequence GFHE; Part 2 Group 4: Treatment Sequence HGEF

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

JNJ-53718678; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2018
• First Posted: October 4, 2018
• Study Start: October 2, 2018
• Primary Completion: December 13, 2019
• Study Completion: December 13, 2019
• Last Updated: February 18, 2020

Record last verified: 2020-02

Locations

BE (1)