A Study to Investigate the Effect of JNJ-64565111 on Cardiac Repolarization (Corrected QT Interval) Compared With Placebo in Healthy Adults: a Thorough ECG Study Employing Placebo, JNJ-64565111, and a Positive Control (Moxifloxacin)

NCT03606057 | Completed Phase 1 FDA Drug

• 2 other identifiers: CR10847764565111OBE1002
• Study Type: interventional
• Target: 188
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effects on placebo-corrected change from baseline QT interval corrected for individual heart rate (QTcI) of JNJ-64565111 close to steady state on Day 26 and on electrocardiogram morphology at supratherapeutic exposures in otherwise healthy overweight/obese adults after 4 weeks of treatment with JNJ 64565111 administered subcutaneously once weekly.

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• Placebo-Corrected Change from Baseline in QT Interval Corrected for Individual Heart Rate (QTcI) on Day 26 Time-Matched Time Points

  Placebo-corrected change from baseline in QT interval corrected for individual heart rate (QTcI) on day 26 time-matched time points will be determined. The mean change from baseline in QTcI for participants who receive placebo will be subtracted from the mean change from baseline in QTcI for participants on JNJ-64565111 at the same time point to generate placebo-corrected change from baseline in QTcI, which will be presented.

  Baseline and Day 26

• Change from Time-Matched Baseline in QTc Interval

  The QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by electrocardiograms (ECG).

  Up to Day 27

• Change from Time-Matched Baseline in Heart Rate (HR)

  The HR will be measured by ECG.

  Up to Day 27

• Change from Time-Matched Baseline in QRS Interval

  The QRS Intervals will be measured by ECG.

  Up to Day 27

• Change from Time-Matched Baseline in PR Interval

  The PR intervals will be measured by ECG.

  Up to Day 27

Secondary Outcomes (7)

• Cardiac Repolarization as Determined by Mean Change from Time-Matched Baseline in QT Interval Corrected for Individual HR (QTcI) on Day 5

  Baseline and Day 5

• Cardiac Repolarization as Determined by Mean Change from Time-Matched Baseline in QT Interval Corrected For HR Using Fridericia's Formula (QTcF) on Day 5 and Day 26

  Baseline, Day 5 and Day 26

• Maximum Observed Serum Concentration (Cmax)

  Days 1, 5, 26 and 27

• Time to Reach Maximum Observed Serum Concentration (Tmax)

  Days 1, 5, 26 and 27

• Average Serum Analyte Concentration (Cavg)

  Days 1, 5, 26 and 27

Study Arms (2)

Treatment Group 1: JNJ-64565111+Moxifloxacin Placebo

EXPERIMENTAL

Participant will receive JNJ-64565111 on days 2, 9, 16, and 23 and moxifloxacin-matching placebo on days 1 and 27.

Drug: JNJ-64565111; Drug: Moxifloxacin-matching Placebo

Treatment Group 2: JNJ-64565111 Matching Placebo+Moxifloxacin

ACTIVE COMPARATOR

Participant will receive JNJ-64565111-matching placebo on days 2, 9, 16, and 23. Participants will also receive moxifloxacin on day 1 and moxifloxacin-matching placebo on day 27 (sequence 2a) or moxifloxacin-matching placebo on day 1 and moxifloxacin on day 27 (sequence 2b) in a nested crossover manner.

Drug: Moxifloxacin; Drug: JNJ-64565111-matching Placebo; Drug: Moxifloxacin-matching Placebo

Interventions

JNJ-64565111 DRUG

Participants will receive JNJ-64565111, subcutaneously on days 2, 9, 16, and 23.

Treatment Group 1: JNJ-64565111+Moxifloxacin Placebo

Moxifloxacin DRUG

Participants will receive moxifloxacin capsule on days 1 or 27 in a nested crossover manner.

Treatment Group 2: JNJ-64565111 Matching Placebo+Moxifloxacin

JNJ-64565111-matching Placebo DRUG

Participants will receive JNJ-64565111-matching Placebo vehicle solution subcutaneously on days 2, 9, 16, and 23.

Treatment Group 2: JNJ-64565111 Matching Placebo+Moxifloxacin

Moxifloxacin-matching Placebo DRUG

Participants will receive moxifloxacin-matching placebo capsule on days 1 and 27 in treatment group 1 and on day 1 or 27 in treatment group 2.

Treatment Group 1: JNJ-64565111+Moxifloxacin Placebo; Treatment Group 2: JNJ-64565111 Matching Placebo+Moxifloxacin

Eligibility Criteria

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

You may qualify if:

• Body mass index (BMI) between 25.0 and 40.0 kilogram per square meter ( kg/m\^2), inclusive, and a body weight of not less than 80 kg
• Blood pressure (BP) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic
• If a woman, must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening
• If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (from screening through Day 56) or until 30 days after the last dose of study drug for participants that withdraw early from the study
• QRS interval of less than or equal to (\<=) 110 milliseconds (ms)
• An average of triplicate 12-lead safety electrocardiogram (ECG) recording, completed within 4 minutes total, consistent with normal cardiac conduction and function at screening, including
• Normal sinus rhythm (heart rate between 45 and 100 beats per minute \[inclusive\])
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval between 350 to 450 ms (inclusive)
• PR interval \<= 200 ms
• ECG morphology consistent with healthy cardiac conduction and function

You may not qualify if:

• Taken any disallowed therapies as defined in a protocol before the planned first dose of study drug
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study
• Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram at screening or at admission to the study site
• Known allergies, hypersensitivity, or intolerance to JNJ-64565111, moxifloxacin, or its excipients
• Hepatitis B or C infection
• History of additional risk factors for torsade de pointes or the presence of a family history of Short QT Syndrome, Long QT Syndrome, sudden unexplained death at a young age (\<= 40 years), or sudden infant death syndrome in a first-degree relative (that is biological parent, sibling, or child)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2018
• First Posted: July 30, 2018
• Study Start: July 13, 2018
• Primary Completion: February 8, 2019
• Study Completion: February 28, 2019
• Last Updated: March 3, 2020

Record last verified: 2020-03

Locations

US (1)