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)

A Randomized, Double-Blind, Parallel, Nested Crossover 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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-64565111; Drug: Moxifloxacin-matching Placebo; Drug: Moxifloxacin; Drug: JNJ-64565111-matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

  1. Normal sinus rhythm (heart rate between 45 and 100 beats per minute [inclusive])
  2. QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval between 350 to 450 ms (inclusive)
  3. PR interval <= 200 ms
  4. ECG morphology consistent with healthy cardiac conduction and function

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment Group 1: JNJ-64565111+Moxifloxacin Placebo; Participant will receive JNJ-64565111 on days 2, 9, 16, and 23 and moxifloxacin-matching placebo on days 1 and 27.	Drug: JNJ-64565111; Participants will receive JNJ-64565111, subcutaneously on days 2, 9, 16, and 23.; Drug: Moxifloxacin-matching Placebo; 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.
ACTIVE_COMPARATOR: Treatment Group 2: JNJ-64565111 Matching Placebo+Moxifloxacin; 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-matching Placebo; 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.; Drug: Moxifloxacin; Participants will receive moxifloxacin capsule on days 1 or 27 in a nested crossover manner.; Drug: JNJ-64565111-matching Placebo; Participants will receive JNJ-64565111-matching Placebo vehicle solution subcutaneously on days 2, 9, 16, and 23.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Repolarization as Determined by Mean Change from Time-Matched Baseline in QT Interval Corrected for Individual HR (QTcI) on Day 5	Mean change from time-matched baseline in QT interval corrected for individual HR (QTcI) on day 5 to determine the effect of JNJ-64565111 on cardiac repolarization.	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	Mean change from time-matched baseline in QT interval corrected for HR using Fridericia's formula (QTcF) will be assessed on day 5 and day 26 to determine the effect of JNJ-64565111 on cardiac repolarization.	Baseline, Day 5 and Day 26
Maximum Observed Serum Concentration (Cmax)	Cmax is defined as the maximum observed serum analyte concentration.	Days 1, 5, 26 and 27
Time to Reach Maximum Observed Serum Concentration (Tmax)	Tmax is defined as actual sampling time to reach maximum observed serum analyte concentration.	Days 1, 5, 26 and 27
Average Serum Analyte Concentration (Cavg)	Cavg is defined as average serum analyte concentration.	Days 1, 5, 26 and 27
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	From signing of the informed consent form (ICF) to end of study (approximately 12 weeks)
QTcI Changes Evaluated Using ECG Assessments versus Serum Concentrations of JNJ-64565111	QTcI changes evaluated using ECG assessments versus serum concentrations of JNJ-64565111 will be quantified. QTcI is a QT interval corrected for heart rate using individual-specific correction formula and QTcI changes will be quantified using a linear or nonlinear mixed effects modeling approach.	Up to Day 27

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 13, 2018
• Primary Completion (ACTUAL): February 8, 2019
• Study Completion (ACTUAL): February 28, 2019

Study Registration Dates

• First Submitted: July 10, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (ACTUAL): July 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 3, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination
• Other Study ID Numbers: CR108477; 64565111OBE1002 (OTHER: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No