Clinical trial NCT03606057: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-07-30
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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)

Primary outcomes:
measure: Placebo-Corrected Change from Baseline in QT Interval Corrected for Individual Heart Rate (QTcI) on Day 26 Time-Matched Time Points
timeFrame: Baseline and Day 26
measure: Change from Time-Matched Baseline in QTc Interval
timeFrame: Up to Day 27
measure: Change from Time-Matched Baseline in Heart Rate (HR)
timeFrame: Up to Day 27
measure: Change from Time-Matched Baseline in QRS Interval
timeFrame: Up to Day 27
measure: Change from Time-Matched Baseline in PR Interval
timeFrame: Up to Day 27
Secondary outcomes:
measure: Cardiac Repolarization as Determined by Mean Change from Time-Matched Baseline in QT Interval Corrected for Individual HR (QTcI) on Day 5
timeFrame: Baseline and Day 5
measure: 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
timeFrame: Baseline, Day 5 and Day 26
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: Days 1, 5, 26 and 27
measure: Time to Reach Maximum Observed Serum Concentration (Tmax)
timeFrame: Days 1, 5, 26 and 27
measure: Average Serum Analyte Concentration (Cavg)
timeFrame: Days 1, 5, 26 and 27
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: From signing of the informed consent form (ICF) to end of study (approximately 12 weeks)
measure: QTcI Changes Evaluated Using ECG Assessments versus Serum Concentrations of JNJ-64565111
timeFrame: Up to Day 27
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: