Safety, Tolerability, Pharmacokinetic and Absolute Bioavailability Study of JNJ-63623872 Administered as an Intravenous Infusion and a 600-Milligram (mg) Oral Dose in Healthy Adults

Healthy Clinical Trial

Official title:

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Absolute Bioavailability of JNJ-63623872 Administered as an Intravenous Infusion and a 600-mg Oral Dose in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02860806
• Other study ID #: CR108196
• Secondary ID: 63623872FLZ10022
• Status: Completed
• Phase: Phase 1
• First received: August 5, 2016
• Last updated: January 26, 2018
• Start date: August 8, 2016
• Est. completion date: June 10, 2017

Study information

• Verified date: January 2018
• Source: Janssen-Cilag International NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to characterize the single-dose pharmacokinetic (PK) of single escalating intravenous (IV) doses of JNJ-63623872 administered as a continuous infusion; to evaluate the safety and tolerability of single escalating IV doses of JNJ-63623872 administered as a continuous infusion; to characterize the single-dose PK of JNJ-63623872 of one selected dose administered as a continuous IV infusion at various durations and to characterize the single- and repeat-dose PK of JNJ-63623872 administered as a continuous infusion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: June 10, 2017
• Est. primary completion date: June 6, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• A female participant (except if postmenopausal) must have a negative serum beta- human chorionic gonadotropin (beta-hCG) pregnancy test at screening and on Day -1 of each treatment period

• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 90 days after discontinuation of study drug

• During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study drug, in addition to the highly effective method of contraception in the female partner, a man regardless of having been vasectomized: 1) who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (example, condom with spermicidal foam/gel/film/cream/suppository), 2) must agree not to donate sperm and 3) who is sexually active with a pregnant women must use a condom

• Must have a Body Mass Index (BMI); weight kilogram [kg]/height^2 [m]^2) between 18.0 and 30.0 kilogram per meter square (kg/m^2) (extremes included) at Screening

• Must have a blood pressure (supine after at least 5 minutes rest and standing after at least 1 minute standing) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic at Screening

Exclusion Criteria:

• 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

• With a past history of heart arrhythmias (extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (example, hypokalemia, family history of long QT Syndrome)

• Has known allergies, hypersensitivity, or intolerance to JNJ-63623872 or its excipients

• With any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria

• With a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs

• Has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening

• Has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-63623872
3 mg/mL solution as intravenous (IV) infusion or a single oral 600 mg dose (2 tablets of 300 mg) under fasted conditions will be administered.
• Placebo
Intravenous infusion of matching placebo.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen-Cilag International NV

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Analyte Concentration (Cmax)	The Cmax is the maximum observed analyte concentration.	Up to 10 days
Primary	Fluctuation Index (FI)	FI is defined as the percentage fluctuation between the Ctrough, morning analyte concentration and the maximum analyte concentration.	Up to 10 days
Primary	Average Analyte Concentration (Cavg)	The Cavg is an average analyte concentration at steady-state over the dosing interval.	Up to 10 days
Primary	Time to Reach the Maximum Observed Analyte Concentration (Tmax)	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Up to 10 days
Primary	Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to 12 Hour (AUC [0-12])	The (AUC [0-12]) is the area under the plasma concentration-time curve from time 0 to 12 hour post dose, calculated by linear-linear trapezoidal summation.	Up to 10 days
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC [0-last])	The (AUC [0-last]) is the area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.	Up to 10 days
Primary	Area Under the Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])	The AUC (0-infinity) is the area under the plasma concentration-time curve from time 0 to infinity, calculated as the sum of AUC(last) and C(last)/lambda(z), where Clast is the last observed measurable (non-BQL) concentration; extrapolations of more than 20.00 percent (%) of the total AUC are reported as approximations.	Up to 10 days
Primary	Elimination Rate Constant (Lambda[z])	Lambda(z) is apparent terminal elimination rate constant, determined by linear regression using the terminal log-linear phase of the log transformed concentration-time curve.	Up to 10 days
Primary	Apparent Terminal Elimination Half-life (t1/2term)	Apparent terminal elimination half-life is defined as 0.693/Lambda[z].	Up to 10 days
Primary	Systemic Clearance (CL)	CL is the total systemic clearance, following intravenous administration.	Up to 10 days
Primary	Apparent Clearance (CL/F)	CL/F is the total apparent clearance, following extravascular administration.	Up to 10 days
Primary	Volume of Distribution (Vd)	The Vd is defined as volume of distribution, following single dose intravenous administration.	Up to 10 days
Primary	Apparent Volume of Distribution (Vd/F)	Vd/F is defined as apparent volume of distribution, following single dose extravascular administration.	Up to 10 days
Primary	Volume of Distribution at Steady-State (Vss)	Vss is defined as apparent volume of distribution at steady-state following intravenous administration.	Up to 10 days
Primary	Observed Accumulation Index (RA abs)	Observed Accumulation Index is calculated by AUC12h, steady state/(AUC12h, single dose).	Up to 10 days
Primary	Morning Trough Analyte Concentration (Ctrough, morning)	Ctrough, morning is defined as observed analyte concentration just prior to the beginning of a dosing interval.	Up to 10 days
Primary	Evening Trough Analyte Concentration (Ctrough, evening)	Ctrough, evening is defined as observed analyte concentration at the end of a dosing interval.	Up to 10 days
Primary	Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability		Up to End of Study (Day 14)
Secondary	Absolute Bioavailability (F[abs])	The F(abs) is calculated as AUC (0-infinity), oral/ AUC (0-infinity), intravenous (iv)*Dose, iv/Dose, oral*100 %, where AUC (0-infinity) is area under the concentration-time curve from time zero to extrapolated infinite time, and D is the dose of administered drug.	Up to 10 days