Clinical trial NCT04223349: A Study of JNJ-70033093 (BMS-986177) in Healthy Adult Participants
Official title: A Phase 1, Open-label Single-dose Crossover, and Double-blind Multiple-dose Parallel Group Study to Characterize the Pharmacokinetics, Safety and Tolerability, and Pharmacodynamics of JNJ-70033093 in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-01-10
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to characterize the pharmacokinetic (PK) of multiple twice-daily doses of JNJ-70033093 in healthy participants and to assess the effects of dosing time and food on the PK of single-dose of JNJ-70033093 in healthy participants.


Eligibility criteria: Inclusion Criteria:

* Healthy on the basis of medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory test results, including serum chemistry, blood coagulation, hematology, and urinalysis performed at screening. If there are abnormalities, the investigator may decide that the abnormalities or deviations from normal are not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
* If a woman, except for postmenopausal women, must have a negative highly sensitive serum (beta human chorionic gonadotropin \[beta-hCG\]) at screening and urine (beta-hCG) pregnancy test on Day -1 of treatment period
* Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
* Body mass index (BMI; weight kilogram per meter square \[kg/m\^2\]) between 18 and 30 kg/m\^2 (inclusive), and body weight not less than 50 kilogram (kg)
* After being supine for 10 minutes, systolic blood pressure between 90 and 140 millimeter of Mercury (mmHg), inclusive; and no higher than 90 mmHg diastolic blood pressure

Exclusion Criteria:

* If a woman, pregnant, breast-feeding or planning to become pregnant during the study
* History of any known illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant or that could prevent, limit or confound the protocol specified assessments. This may include but is not limited to any known bleeding or clotting disorder, a history of arterial or venous thrombosis, liver or renal dysfunction, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic abnormalities, metabolic disturbances, or poor venous access
* Participants with current hepatitis B infection (confirmed by hepatitis B surface antigen \[HBsAg\]), or hepatitis C infection (confirmed by hepatitis C virus \[HCV\] antibody), or human immunodeficiency virus type-1 (HIV-1) or HIV-2 infection at study screening
* History of, or a reason to believe a participant has a history of, drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM V) criteria within the past 1 year, which in the investigator's opinion would compromise participant safety and/or compliance with the study procedures
* History of any clinically significant drug or food allergies (such as anaphylaxis or hepatotoxicity) and known allergy to the study drugs or any of the excipients of the formulation. History of allergy to or unwillingness to consume any component of the high-fat breakfast menu to be provided in this study
* Clinically significant abnormal values for hematology, coagulation, clinical chemistry or urinalysis at Screening or on Day -1 prior to the first dosing as determined by the investigator or appropriate designee. Any of the following laboratory results outside of the ranges specified below at screening or Day -1 prior to first dosing, confirmed by repeat: Hemoglobin or hematocrit \< lower limit of normal; Platelet count \< lower limit of normal; activated partial thromboplastin time (aPTT), or prothrombin time (PT) greater than (\>) 1.2 × upper limit of normal (ULN)
* Any of the following on 12-lead ECG and assessment of QT interval prior to study treatment administration, confirmed by repeat at screening and Day -1 of treatment period: Heart rate \>100 beats per minute (bpm); PR \>= 210 milli second (ms); QRS \>=120 ms; QTcF \>= 450 ms for male and \>= 470 ms for female

Primary outcomes:
measure: Part 1: Maximum Observed Analyte Concentration (Cmax) of JNJ-70033093
timeFrame: Up to Day 9
measure: Part 1: Time to Reach the Maximum Observed Analyte Concentration (Tmax) of JNJ-70033093
timeFrame: Up to Day 9
measure: Part 1: Area Under the Analyte Concentration-time Curve from Time Zero to 12 Hours (AUC[0-12h]) of JNJ-70033093
timeFrame: 12 hours postdose (Day 1)
measure: Part 1: Apparent Terminal Elimination Half-life (t[1/2]) of JNJ-70033093
timeFrame: Up to Day 9
measure: Part 2: Maximum Observed Analyte Concentration (Cmax) of JNJ-70033093
timeFrame: Up to Day 9
measure: Part 2: Area Under the Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUC [0-last]) of JNJ-70033093
timeFrame: Up to Day 9
measure: Part 2: Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of JNJ-70033093
timeFrame: Up to Day 9
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 51 days
measure: Number of Participants with Vital Sign Abnormalities
timeFrame: Up to 51 days
measure: Number of Participants with Abnormal Electrocardiogram (ECG) Findings
timeFrame: Up to 51 days
measure: Number of Participants with Abnormal Laboratory Findings
timeFrame: Up to 51 days
measure: Relationship Between JNJ-70033093 Plasma Concentrations and QTc After Multiple Doses of JNJ-70033093
timeFrame: Up to Day 9
measure: Percentage Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
timeFrame: Baseline up to Day 9 (Part 1); Baseline up to Day 11 (Part 2)
measure: Percentage Change from Baseline in Factor XI Clotting Activity
timeFrame: Baseline up to Day 9 (Part 1); Baseline up to Day 11 (Part 2)
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: