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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)

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ClinicalTrials.gov Identifier: NCT03606057
Recruitment Status : Completed
First Posted : July 30, 2018
Last Update Posted : February 27, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: JNJ-64565111 Drug: Moxifloxacin Drug: JNJ-64565111-matching Placebo Drug: Moxifloxacin-matching Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 188 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : July 13, 2018
Actual Primary Completion Date : February 8, 2019
Actual Study Completion Date : February 20, 2019

Resource links provided by the National Library of Medicine


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
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.

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.




Primary Outcome Measures :
  1. Placebo-Corrected Change from Baseline in QT Interval Corrected for Individual Heart Rate (QTcI) on Day 26 Time-Matched Time Points [ Time Frame: Baseline and Day 26 ]
    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.

  2. Change from Time-Matched Baseline in QTc Interval [ Time Frame: Up to Day 27 ]
    The QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by electrocardiograms (ECG).

  3. Change from Time-Matched Baseline in Heart Rate (HR) [ Time Frame: Up to Day 27 ]
    The HR will be measured by ECG.

  4. Change from Time-Matched Baseline in QRS Interval [ Time Frame: Up to Day 27 ]
    The QRS Intervals will be measured by ECG.

  5. Change from Time-Matched Baseline in PR Interval [ Time Frame: Up to Day 27 ]
    The PR intervals will be measured by ECG.


Secondary Outcome Measures :
  1. Cardiac Repolarization as Determined by Mean Change from Time-Matched Baseline in QT Interval Corrected for Individual HR (QTcI) on Day 5 [ Time Frame: Baseline and 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.

  2. 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 [ Time Frame: Baseline, 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.

  3. Maximum Observed Serum Concentration (Cmax) [ Time Frame: Days 1, 5, 26 and 27 ]
    Cmax is defined as the maximum observed serum analyte concentration.

  4. Time to Reach Maximum Observed Serum Concentration (Tmax) [ Time Frame: Days 1, 5, 26 and 27 ]
    Tmax is defined as actual sampling time to reach maximum observed serum analyte concentration.

  5. Average Serum Analyte Concentration (Cavg) [ Time Frame: Days 1, 5, 26 and 27 ]
    Cavg is defined as average serum analyte concentration.

  6. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From signing of the informed consent form (ICF) to end of study (approximately 12 weeks) ]
    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.

  7. QTcI Changes Evaluated Using ECG Assessments versus Serum Concentrations of JNJ-64565111 [ Time Frame: Up to Day 27 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03606057


Locations
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United States, Arizona
Celerion
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03606057     History of Changes
Other Study ID Numbers: CR108477
64565111OBE1002 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: February 27, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs