A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of JNJ-64264681 in Healthy Male and Female Participants

Healthy Clinical Trial

Official title:

A Double-blind, Placebo-controlled, Randomized, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of JNJ-64264681 in Healthy Male and Female Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03607513
• Other study ID #: CR108457
• Secondary ID: 2018-000428-3264
• Status: Completed
• Phase: Phase 1
• Start date: July 31, 2018
• Est. completion date: August 9, 2019

Study information

• Verified date: August 2019
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of JNJ-64264681 in healthy participants after single and multiple oral doses.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: August 9, 2019
• Est. primary completion date: August 9, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 58 Years

Eligibility

Inclusion Criteria:

• Participant must have a body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m^2) (BMI = weight[kg]/height[m]^2), and a body weight of not less than 50 kilogram (kg)

• Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead Electrocardiogram (ECG) performed at screening and Day -1

• Participant must be healthy on the basis of clinical laboratory tests performed at screening and Day -1. If the results of the serum chemistry panel, coagulation, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator

• 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

• Female participants must not be of childbearing potential by fulfilling 1 of the criteria below: a) Be over 45 years of age with no menses for 12 months without an alternative medical cause, with screening follicle stimulating hormone (FSH) levels of greater than (>)40 International Units Per Liter (IU/L) or milli-international units per milliliter (mIU/mL). b) Be permanently surgically sterile. Permanent surgical sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy. Documentation of FSH levels is not required in the case of surgical sterility

Exclusion Criteria:

• Participant has current, or history of clinically significant medical illness including, but not limited to, liver or renal insufficiency, significant cardiac (including heart valve disease), vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances

• Participant has a history of abnormal bleeding or bruising

• Participant has a history of atrial fibrillation or history of arrhythmias

• Participant has history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence)

• Participant has known allergies, hypersensitivity, or intolerance to polyethylene glycol 400 (PEG400) (vehicle for JNJ-64264681 for oral solution dosing) for participant in a cohort where study drug is to be dosed as an oral solution, or to microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, silica dioxide, sodium lauryl sulfate, magnesium stearate, or gelatin (excipients in the solid dose formulation (capsule) of JNJ-64264681) for participant in a solid dose formulation cohort

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-64264681
For all cohorts except the solid dose formulation cohort, JNJ-64264681 wlll be administered as oral solution. For the solid dose formulation cohort, JNJ-64264681 will be provided as capsules for oral administration.
• Placebo
Matching placebo to JNJ-64264681 will be administered as oral solution.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

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	Single Ascending Dose (SAD): Number of Participants with Adverse Events	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.	Up to Day 14
Primary	Multiple Ascending Dose (MAD): Number of Participants with Adverse Events	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.	Up to Day 24
Primary	SAD: Maximum Observed Plasma Concentration (Cmax)	Cmax is the maximum observed plasma JNJ-64264681 concentration.	Up to Day 4
Primary	MAD: Maximum Observed Plasma Concentration (Cmax)	Cmax is the maximum observed plasma JNJ-64264681 concentration.	Up to Day 13
Primary	SAD: Time to Reach Maximum Observed Plasma Concentration (Tmax)	Tmax is defined as actual sampling time to reach maximum observed concentration.	Up to Day 4
Primary	MAD: Time to Reach Maximum Observed Plasma Concentration (Tmax)	Tmax is defined as actual sampling time to reach maximum observed concentration.	Up to Day 13
Primary	SAD: Time to Last Quantifiable Plasma Concentration (Tlast)	The Tlast is the time to last observed quantifiable plasma concentration.	Up to Day 4
Primary	MAD: Time to Last Quantifiable Plasma Concentration (Tlast)	The Tlast is the time to last observed quantifiable plasma concentration.	Up to Day 13
Primary	SAD: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24])	AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.	Day 1: Up to 24 hours post-dose
Primary	MAD: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24])	AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.	Day 1: Up to 24 hours post-dose
Primary	SAD: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration (AUClast)	AUClast is defined as area under the plasma JNJ-64264681 concentration-time curve from time 0 to time of the last observed quantifiable concentration.	Up to Day 4
Primary	MAD: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)	AUCtau is area under the plasma JNJ-64264681 concentration-time curve during a dosing interval (tau) at steady-state.	Day 10
Primary	SAD: Area Under the Plasma 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 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.	Up to Day 3
Primary	SAD: Apparent Elimination Half-life (t1/2)	t1/2 is apparent elimination half-life of JNJ-64264681 associated with the terminal slope (z) of the semi-logarithmic drug concentration-time curve.	Up to Day 3
Primary	MAD: Apparent Elimination Half-life (t1/2)	t1/2 is apparent elimination half-life of JNJ-64264681 associated with the terminal slope (z) of the semi-logarithmic drug concentration-time curve.	Up to Day 13
Primary	MAD: Accumulation Ratio	MAD: Accumulation Ratio obtained by dividing AUC of JNJ-64264681 at two different time points.	Up to Day 13