Healthy
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of JNJ-64179375 in Part 1 (Intravenous dose) and Part 3 (Subcutaneous dose) and potential for reversibility of JNJ-64179375 induced Pharmacodynamic effects on coagulation parameters and platelet function (Part 2) in healthy male participants.
Interventions
DRUGJNJ-64179375
During part 1, participants will receive a single ascending Intravenous dose of JNJ-64179375 ranging from (0.03 mg/kg to 5.0 mg/kg). In Part 2, participants will receive a 2.5 mg/kg or highest tolerable dose if lower than 2.5 mg/kg of JNJ-64179375. In Part 3, participants will receive a Single Subcutaneous (SC) dose of 1.0 mg/kg or highest tolerable dose if less than 1.0 mg/kg of JNJ-64179375.
DRUGPlacebo
Participants will randomly receive matching placebo in all 3 Parts on day 1 administered via IV Route (for Part 1 and 2) and SC route (for Part 3).
DRUG4 Factor Prothrombin Complex Concentrate (PCC)
Following a single dose of JNJ-64179375, participants will receive a single IV dose of 4 factor-PCC.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index \[weight kilogram per meter square (kg/m\^2)\] between 18 and 30 kg/m\^2 (inclusive), and body weight greater than 50 kilogram (kg) but less than 100 kg * Generally in good health on the basis of physical examination, medical history, vital signs, laboratory tests, and electrocardiogram (ECG) performed at screening and/or prior to administration of the initial dose of study drug * Must sign an informed consent form (ICF) indicating that he understands the purpose of, and procedures required for, the study and is willing to participate in the study * contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies * willing and able to adhere to the study visit schedule and other requirements, prohibitions, and restrictions specified in this protocol through the Day 113 visit
Exclusion criteria
* Acute illness, including an upper respiratory infection (with or without fever), within 7 days prior to study drug administration or have had a major illness or hospitalization within 1 month prior to study drug administration * Clinically significant abnormal values for coagulation, hematology, clinical chemistry or urinalysis at screening or on Day -1 (at admission to the clinical research unit) as determined by the investigator or appropriate designee * Have smoked tobacco or nicotine-related products within 6 months prior to dosing or does not agree to refrain through Day 113 * Donated blood or blood products or had substantial loss of blood \[more than 500 milliliter (mL)\] within 3 months before the first administration of study drug or intends to donate or donates blood or blood products during the study until 30 days after completion * History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, bleeding or thrombotic disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability | Up to Day 113 | — |
| Part 3: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability | Up to Day 113 | — |
| Part 2: Change From Baseline in Potential for Reversibility of the JNJ-64179375 Induced Pharmacodynamic Effects on Coagulation Parameters | Baseline and Day 1 | Change in Potential for Reversibility of the JNJ-64179375 will be assessed by assessing the change in thrombin time as coagulation parameter. |
| Part 2: Change From Baseline in Potential for Reversibility of the JNJ-64179375 Induced Pharmacodynamic Effects on Platelet Function | Baseline and Day 1 | Platelet function will be assessed by measuring platelet activation and aggregation in response to thrombin and other agonists and with the platelet function analyzer (PFA)100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Total Systemic Clearance (CL) of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | CL is defined as total systemic clearance after intravenous administration of JNJ-64179375. |
| Part 1: Apparent Volume of Distribution at Terminal Phase After Intravenous Administration (Vz) of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | Vz is defined as the Apparent volume of distribution at terminal phase after intravenous administration. |
| Part 3: Time to Reach Maximum Observed Concentration (Tmax) of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | Tmax is defined as time to the maximum observed plasma concentration of JNJ-64179375. |
| Part 3: Total Systemic Clearance Over Bioavailability After Subcutaneous (SC) Administration (CL/F) of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | CL/F is defined as total systemic clearance over bioavailability after SC administration. |
| Part 3: Apparent Volume of Distribution at Terminal Phase Over Bioavailability After Subcutaneous Administration (Vz/F) of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | (Vz/F) is defined as Apparent Volume of distribution at terminal phase over bioavailability after SC administration of JNJ-64179375. |
| Part 3: Absolute Bioavailability (F) After Subcutaneous Administration of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | F is defined as absolute bioavailability after SC administration of JNJ-64179375. |
| Part 1 and 3: Immunogenicity of JNJ-64179375 | Predose, Day 7, 14, 29, 57, 85 and 113 | Plasma samples will be collected and screened for antibodies binding to JNJ-64179375 and the titer of confirmed positive samples will be reported. |
| Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-64179375 in presence of 4-factor prothrombin complex concentrate (PCC) | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | Cmax is defined as maximum observed plasma concentration of JNJ-64179375. |
| Part 1 and 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | Cmax is defined as maximum observed plasma concentration of JNJ-64179375. |
| Part 2: Area Under the Plasma ConcentrationTime Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64179375 in the presence of 4-factor PCC | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | The (AUC \[0-infinity\]) is defined as Area under the plasma concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase. |
| Part 2: Terminal Half Life [t(1/2)] of JNJ-64179375 in the presence of 4-factor PCC | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | Half life \[t(1/2)\] is associated with the terminal slope (lambda \[z\]) of the semilogarithmic drug concentration time curve, calculated as 0.693/lambda(z). |
| Part 2: Total Systemic Clearance (CL) of JNJ-64179375 in the presence of 4-factor PCC | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | CL is defined as total systemic clearance after intravenous administration of JNJ-64179375. |
| Part 2: Apparent Volume of Distribution at Terminal Phase After Intravenous Administration (Vz) of JNJ-64179375 in the presence of 4-factor PCC | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | Vz is defined as the Apparent volume of distribution at terminal phase after intravenous administration. |
| Part 2: Immunogenicity of JNJ-64179375 in the presence of 4-factor PCC | Predose, Day 7, 14, 29, 57, 85 and 113 | Plasma samples will be collected and screened for antibodies binding to JNJ-64179375 and the titer of confirmed positive samples will be reported. |
| Part 2: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability | Baseline to End of treatment (Day 113) | — |
| Part 1 and 3: Pharmacodynamic Effect of JNJ-64179375 on Platelet Function | Predose, Day 1, 2, 4, 7, 14, 29, 57 and 113 | Platelet function will be assessed by measuring platelet activation and aggregation in response to thrombin and other agonists and with the platelet function analyzer (PFA)-100. |
| Part 1 and 3: Pharmacodynamic Effect of JNJ-64179375 on Coagulation Parameters | Predose, Day 1, 2, 4, 7, 14, 29, 57 and 113 | The pharmacodynamic effect of JNJ-64179375 on coagulation parameters will be assessed by measuring the change in thrombin time. |
| Part 2: Area Under the Plasma ConcentrationTime Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC [0-last]) of JNJ-64179375 in the presence of 4-factor PCC | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | The (AUC \[0-last\]) is defined as Area under the plasma concentration versus time curve from time 0 to the time corresponding to the last quantifiable serum concentration of JNJ-64179375 |
| Part 1 and 3: Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | The (AUC \[0-last\]) is defined as Area under the plasma concentration versus time curve from time 0 to the time corresponding to the last quantifiable serum concentration of JNJ-64179375. |
| Part 1 and 3: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | The (AUC \[0-infinity\]) is defined as Area under the plasma concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase. |
| Part 1 and 3: Terminal Half-Life (t1/2) of JNJ-64179375 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 | Half-life (t\[1/2\]) is associated with the terminal slope (lambda \[z\]) of the semi-logarithmic drug concentration-time curve, calculated as 0.693/lambda(z). |
Countries
Belgium
Outcome results
None listed