A 3-Part First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of JNJ-64179375 in Healthy Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Healthy
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 80
- Primary Endpoint
- Part 1: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
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.
Intervention: Placebo
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.
Intervention: JNJ-64179375
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.
Intervention: JNJ-64179375
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.
Intervention: Placebo
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.
Intervention: JNJ-64179375
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.
Intervention: Placebo
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.
Intervention: JNJ-64179375
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.
Intervention: Placebo
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.
Intervention: JNJ-64179375
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.
Intervention: Placebo
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.
Intervention: Placebo
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.
Intervention: JNJ-64179375
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.
Intervention: Placebo
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.
Intervention: JNJ-64179375
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.
Intervention: Placebo
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.
Intervention: JNJ-64179375
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.
Intervention: Placebo
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.
Intervention: JNJ-64179375
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.
Intervention: 4 Factor Prothrombin Complex Concentrate (PCC)
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.
Intervention: JNJ-64179375
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Part 1: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability
Time Frame: Up to Day 113
Part 3: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability
Time Frame: Up to Day 113
Part 2: Change From Baseline in Potential for Reversibility of the JNJ-64179375 Induced Pharmacodynamic Effects on Coagulation Parameters
Time Frame: 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
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Part 1: Total Systemic Clearance (CL) 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(Predose, Day 1, 2, 4, 7, 10, 14, 22, 29, 43, 57, 85 and 113)
- Part 1 and 3: Immunogenicity of JNJ-64179375(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)(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(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(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(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(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(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(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(Predose, Day 1, 2, 4, 7, 14, 29, 57 and 113)
- Part 1 and 3: Pharmacodynamic Effect of JNJ-64179375 on Coagulation Parameters(Predose, Day 1, 2, 4, 7, 14, 29, 57 and 113)