A Study to Evaluate Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of JNJ-64179375 in Healthy Male Subjects
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Cohort 1 (0.03 mg/kg of JNJ-64179375 or Placebo) 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. |
Drug: JNJ-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.
Drug: Placebo
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).
|
| Experimental: Part 1: Cohort 2 (0.1 mg/kg of JNJ-64179375 or Placebo) 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. |
Drug: JNJ-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.
Drug: Placebo
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).
|
| Experimental: Part 1: Cohort 3 (0.3 mg/kg of JNJ-64179375 or Placebo) 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. |
Drug: JNJ-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.
Drug: Placebo
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).
|
| Experimental: Part 1: Cohort 4 (1.0 mg/kg of JNJ-64179375 or Placebo) 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. |
Drug: JNJ-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.
Drug: Placebo
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).
|
| Experimental: Part 1: Cohort 5 (2.5 mg/kg of JNJ-64179375 or Placebo) 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. |
Drug: JNJ-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.
Drug: Placebo
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).
|
| Experimental: Part 1: Cohort 6 (5.0 mg/kg of JNJ-64179375 or Placebo) 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. |
Drug: JNJ-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.
Drug: Placebo
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).
|
| Experimental: Part 1: Cohort 7 (Escalation Dose of JNJ-64179375 or Placebo) Dose escalation will proceed until the toxicology study exposure limits or a highest tolerable dose will be reached. |
Drug: JNJ-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.
Drug: Placebo
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).
|
| Experimental: Part 1: Cohort 8 (Escalation Dose of JNJ-64179375 or Placebo) Dose escalation will proceed until the toxicology study exposure limits or a highest tolerable dose will be reached. |
Drug: JNJ-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.
Drug: Placebo
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).
|
| Experimental: Part 2: Reversal Cohort :(50 IU/kg of 4-factor PCC) 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. |
Drug: JNJ-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.
Drug: Placebo
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).
Drug: 4 Factor Prothrombin Complex Concentrate (PCC)
Following a single dose of JNJ-64179375, participants will receive a single IV dose of 4 factor-PCC.
|
| Experimental: Part 3: Subcutaneous Cohort (1.0 mg/kg of JNJ-64179375) 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. |
Drug: JNJ-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.
Drug: Placebo
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).
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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).
- 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 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 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Body mass index [weight kilogram per meter square (kg/m2)] between 18 and 30 kg/m2 (inclusive), and body weight greater than 50 kilogram (kg) but less than 100 kg
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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
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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
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contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies
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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
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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
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Have smoked tobacco or nicotine-related products within 6 months prior to dosing or does not agree to refrain through Day 113
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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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Merksem | Belgium |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR108238
- 64179375EDI1001
- 2016-003006-13