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| ID | Type | Description | Link |
|---|---|---|---|
| 64179375EDI1001 | Other Identifier | Janssen Research & Development, LLC | |
| 2016-003006-13 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Cohort 1 (0.03 mg/kg of JNJ-64179375 or Placebo) | Experimental | Participants in a ratio of 3:1 will receive a single 0.03 milligram per kilogram (mg/kg) intravenous (IV) dose of JNJ-64179375 or matching placebo on Day 1. |
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| Part 1: Cohort 2 (0.1 mg/kg of JNJ-64179375 or Placebo) | Experimental | Participants in a ratio of 3:1 will receive a single 0.1 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1. |
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| Part 1: Cohort 3 (0.3 mg/kg of JNJ-64179375 or Placebo) | Experimental | Participants in a ratio of 3:1 will receive a single 0.3 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1. |
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| Part 1: Cohort 4 (1.0 mg/kg of JNJ-64179375 or Placebo) | Experimental | Participants in a ratio of 3:1 will receive a single 1.0 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1. |
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| Part 1: Cohort 5 (2.5 mg/kg of JNJ-64179375 or Placebo) | Experimental | Participants in a ratio of 3:1 will receive a single 2.5 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JNJ-64179375 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Change in Potential for Reversibility of the JNJ-64179375 will be assessed by assessing the change in thrombin time as coagulation parameter. | Baseline and Day 1 |
| Part 2: Change From Baseline in Potential for Reversibility of the JNJ-64179375 Induced Pharmacodynamic Effects on Platelet Function | 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. | Baseline and Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1 and 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-64179375 | Cmax is defined as maximum observed plasma concentration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Merksem | Belgium |
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| Part 1: Cohort 6 (5.0 mg/kg of JNJ-64179375 or Placebo) | Experimental | Participants in a ratio of 3:1 will receive a single 5.0 mg/kg IV dose of JNJ-64179375 or matching placebo on Day 1. |
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| Part 1: Cohort 7 (Escalation Dose of JNJ-64179375 or Placebo) | Experimental | Dose escalation will proceed until the toxicology study exposure limits or a highest tolerable dose will be reached. |
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| Part 1: Cohort 8 (Escalation Dose of JNJ-64179375 or Placebo) | Experimental | Dose escalation will proceed until the toxicology study exposure limits or a highest tolerable dose will be reached. |
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| Part 2: Reversal Cohort :(50 IU/kg of 4-factor PCC) | Experimental | Participants will receive a 2.5 mg/kg of JNJ-64179375 or highest tolerable dose if lower than 2.5 mg/kg followed by administration of a single IV 50 International Unit per kilogram (IU/Kg) dose of a 4 factor prothrombin complex concentrate (PCC) or matching placebo on Day 1. |
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| Part 3: Subcutaneous Cohort (1.0 mg/kg of JNJ-64179375) | Experimental | 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 or matching placebo on Day 1. |
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| Placebo | Drug | 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). |
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| 4 Factor Prothrombin Complex Concentrate (PCC) | Drug | Following a single dose of JNJ-64179375, participants will receive a single IV dose of 4 factor-PCC. |
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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. |
| Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 1 and 3: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64179375 | 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. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 1 and 3: Terminal Half-Life (t1/2) of JNJ-64179375 | 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). | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 1: Total Systemic Clearance (CL) of JNJ-64179375 | CL is defined as total systemic clearance after intravenous administration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 1: Apparent Volume of Distribution at Terminal Phase After Intravenous Administration (Vz) of JNJ-64179375 | Vz is defined as the Apparent volume of distribution at terminal phase after intravenous administration. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 3: Time to Reach Maximum Observed Concentration (Tmax) of JNJ-64179375 | Tmax is defined as time to the maximum observed plasma concentration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 3: Total Systemic Clearance Over Bioavailability After Subcutaneous (SC) Administration (CL/F) of JNJ-64179375 | CL/F is defined as total systemic clearance over bioavailability after SC administration. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 3: Apparent Volume of Distribution at Terminal Phase Over Bioavailability After Subcutaneous Administration (Vz/F) of JNJ-64179375 | (Vz/F) is defined as Apparent Volume of distribution at terminal phase over bioavailability after SC administration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 3: Absolute Bioavailability (F) After Subcutaneous Administration of JNJ-64179375 | F is defined as absolute bioavailability after SC administration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 1 and 3: Immunogenicity of JNJ-64179375 | Plasma samples will be collected and screened for antibodies binding to JNJ-64179375 and the titer of confirmed positive samples will be reported. | Predose, Day 7, 14, 29, 57, 85 and 113 |
| Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-64179375 in presence of 4-factor prothrombin complex concentrate (PCC) | Cmax is defined as maximum observed plasma concentration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| 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 | 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 | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| 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 | 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. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 2: Terminal Half Life [t(1/2)] of JNJ-64179375 in the presence of 4-factor PCC | 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). | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 2: Total Systemic Clearance (CL) of JNJ-64179375 in the presence of 4-factor PCC | CL is defined as total systemic clearance after intravenous administration of JNJ-64179375. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 2: Apparent Volume of Distribution at Terminal Phase After Intravenous Administration (Vz) of JNJ-64179375 in the presence of 4-factor PCC | Vz is defined as the Apparent volume of distribution at terminal phase after intravenous administration. | Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113 |
| Part 2: Immunogenicity of JNJ-64179375 in the presence of 4-factor PCC | Plasma samples will be collected and screened for antibodies binding to JNJ-64179375 and the titer of confirmed positive samples will be reported. | Predose, Day 7, 14, 29, 57, 85 and 113 |
| 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 | 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. | Predose, Day 1, 2, 4, 7, 14, 29, 57 and 113 |
| Part 1 and 3: Pharmacodynamic Effect of JNJ-64179375 on Coagulation Parameters | The pharmacodynamic effect of JNJ-64179375 on coagulation parameters will be assessed by measuring the change in thrombin time. | Predose, Day 1, 2, 4, 7, 14, 29, 57 and 113 |