Clinical trial NCT02658825: A Study to Evaluate the Effect of JNJ-63623872 on Cardiac Repolarization Interval in Healthy Participants
Official title: A Double-blind, Double-dummy, Randomized, 3-Period Cross-over, Placebo- and Positive-controlled Study to Evaluate the Effect of JNJ-63623872 on Cardiac Repolarization Interval in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
JNJ-63623872
Moxifloxacin
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-01-20
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effect of JNJ-63623872 on the QT/QTc interval at supratherapeutic exposure in healthy participants (Panel 2).

Detailed description: This is a two-part Phase 1 study consisting of a dose escalation part (Panel 1) and a thorough QT (TQT) part (Panel 2). Panel 1 will be a double-blind (neither the researchers nor the participants know what treatment the participant is receiving), randomized (study medication assigned to participants by chance), placebo-controlled dose escalation study in healthy participants to determine the safety, tolerability and pharmacokinetics of JNJ-63623872 after administration of single doses of 2400 milligrams (mg) and 3000 mg under fasted conditions. The final dose to be used in the Panel 2 will be determined based on the results of this dose escalation part. An interim analysis will be conducted on Panel 1 to select the dose for Panel 2. Panel 2 will be a double-blind, double-dummy, randomized, 3-period crossover (the same medications provided to all participants but in different sequence), placebo- and positive controlled study to evaluate the effect of JNJ-63623872 on the QT/QTc interval in healthy participants. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Each participant must sign an Informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study
* Participant must be willing and able to adhere to the prohibitions and restrictions specified in the protocol
* A female participant must agree not to donate eggs (ova, oocytes) during the study and for at least 90 days after receiving the (last dose of) study drug
* A male participant who is sexually active with a woman of childbearing potential must agree to use two effective methods of contraception during the study and for at least 90 days after receiving the (last dose of) study drug, and a male participant must also not donate sperm during the study and for at least 90 days after receiving the (last dose of) study drug
* Participants must be non-smokers for at least 3 months prior to Screening
* Participants must have a Body Mass Index (BMI) between 18.0 and 30.0 kilogram per meter\^2 (kg/m\^2) (inclusive) at Screening

Exclusion Criteria:

* Participant has a history of current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results
* Participants with a history of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardias, and heart blocks
* Participants with unusual T wave morphology (such as bifid T wave) likely to interfere with QTc measurements
* Participants with electrolyte abnormalities (hypokalemia, hypocalcemia, hypomagnesemia) of grade 2 or above within 21 days prior to the (first) intake of the study drug
* Participants with a breast implant or a history of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues
* Participant has taken any disallowed therapies (Concomitant Therapy) before the planned (first) intake of study drug
* Participant has known allergies, hypersensitivity, or intolerance to JNJ-63623872, moxifloxacin or its excipients

Primary outcomes:
measure: Change From Baseline in Corrected QT Interval (QTc) at Different Time Points
timeFrame: 45, 30 and 15 minutes predose and 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose on Day 1
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax)
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, Treatment C of Dose Level 2 (Panel 1) and Treatment E (Panel 2)
measure: Time To Reach The Maximum Observed Concentration (Tmax)
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, Treatment C of Dose Level 2 (Panel 1) and Treatment E (Panel 2)
measure: Observed Concentration at 24 Hours Post Dosing (C24h)
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinite Time (AUC[0-infinity])
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
measure: Area Under the Concentration Versus Time Curve (AUC) From Time of Administration up to 24 Hours Post Dosing (AUC24h)
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 1 of Treatment E (Panel 2)
measure: Elimination Rate Constant (Lambda[z])
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
measure: Apparent Terminal Elimination Half-life (t1/2term)
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 120 hours post-dose on Day 1 of Treatment A of Dose Level 1, and Treatment C of Dose Level 2 (Panel 1)
measure: Number of Participants with Adverse Events (AEs) and Serious AEs
timeFrame: Screening up to Follow-up (10 to 14 days after last study drug administration)
Other outcomes:
Locations:
city: Antwerp
country: Belgium
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: