A Study to Evaluate the Effect of JNJ-63623872 on Cardiac Repolarization Interval in Healthy Participants

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02658825
• Other study ID #: CR108108
• Secondary ID: 63623872FLZ10052
• Status: Completed
• Phase: Phase 1
• First received: January 15, 2016
• Last updated: June 15, 2016
• Start date: January 2016
• Est. completion date: April 2016

Study information

• Verified date: June 2016
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-63623872 2400 milligram (mg)
Participants will receive JNJ-63623872 2400 mg tablet orally once on Day 1 of Panel 1.
• JNJ-63623872 3000 mg
Participants will receive JNJ-63623872 3000 mg tablet orally once on Day 1 of Panel 1.
• JNJ-63623872
Participants will receive JNJ-63623872 dose selected in Panel 1 tablet orally once on Day 1 of Panel 2.
• Moxifloxacin
Participants will receive moxifloxacin 400 mg capsule orally once on Day 1 of Panel 2.
• Placebo (Matching with JNJ-63623872 2400 mg)
Participants will receive placebo (matching with JNJ-63623872 2400 mg) tablet orally once on Day 1 of Panel 1.
• Placebo (Matching with JNJ-63623872 3000 mg)
Participants will receive placebo (matching with JNJ-63623872 3000 mg) tablet orally once on Day 1 of Panel 1 and 2.
• Placebo (Matching with JNJ-63623872 Dose)
Participants will receive placebo (matching with JNJ-63623872 dose) tablet orally once on Day 1 of Panel 2.
• Placebo (Matching with Moxifloxacin)
Participants will receive placebo (matching with Moxifloxacin) tablet orally once on Day 1 of Panel 2.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Corrected QT Interval (QTc) at Different Time Points	Electrocardiogram will be collected by Holter monitoring. The measured QT data will be corrected for heart rate using Fridericia (QTcF), Bazett (QTcB), and study-specific power (QTcP) correction methods. The QTcF as primary correction method.	45, 30 and 15 minutes predose and 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours postdose on Day 1	No
Secondary	Maximum Observed Concentration (Cmax)	The Cmax is the maximum observed concentration.	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)	No
Secondary	Time To Reach The Maximum Observed Concentration (Tmax)	The Tmax is the actual sampling time to reach the maximum observed concentration.	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)	No
Secondary	Observed Concentration at 24 Hours Post Dosing (C24h)	The C24h is the observed concentration at 24 hours post dosing.	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)	No
Secondary	Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	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)	No
Secondary	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinite Time (AUC[0-infinity])	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	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)	No
Secondary	Area Under the Concentration Versus Time Curve (AUC) From Time of Administration up to 24 Hours Post Dosing (AUC24h)	The AUC24h is the area under the concentration versus time curve (AUC) from time of administration up to 24 hours post dosing.	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)	No
Secondary	Elimination Rate Constant (Lambda[z])	Lambda (z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.	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)	No
Secondary	Apparent Terminal Elimination Half-life (t1/2term)	The T1/2term is the apparent terminal elimination half-life, calculated as 0.693/Lambda(z).	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)	No
Secondary	Number of Participants with Adverse Events (AEs) and Serious AEs	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Screening up to Follow-up (10 to 14 days after last study drug administration)	Yes