Skip to main content
OpenTrials
Completed

NCT Number: NCT02949206

A Study to Evaluate Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of JNJ-64179375 in Healthy Male Subjects

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Merksem, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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).

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.

Primary outcomes

  1. Part 1: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability

    Time frame: Up to Day 113

  2. Part 3: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability

    Time frame: Up to Day 113

  3. 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.

  4. 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

  1. Part 1 and 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-64179375

    Time frame: 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.

  2. 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

    Time frame: 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.

  3. Part 1 and 3: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64179375

    Time frame: 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.

  4. Part 1 and 3: Terminal Half-Life (t1/2) of JNJ-64179375

    Time frame: 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).

  5. Part 1: Total Systemic Clearance (CL) of JNJ-64179375

    Time frame: 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.

  6. Part 1: Apparent Volume of Distribution at Terminal Phase After Intravenous Administration (Vz) of JNJ-64179375

    Time frame: 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.

  7. Part 3: Time to Reach Maximum Observed Concentration (Tmax) of JNJ-64179375

    Time frame: 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.

  8. Part 3: Total Systemic Clearance Over Bioavailability After Subcutaneous (SC) Administration (CL/F) of JNJ-64179375

    Time frame: 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.

  9. Part 3: Apparent Volume of Distribution at Terminal Phase Over Bioavailability After Subcutaneous Administration (Vz/F) of JNJ-64179375

    Time frame: 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.

  10. Part 3: Absolute Bioavailability (F) After Subcutaneous Administration of JNJ-64179375

    Time frame: 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.

  11. Part 1 and 3: Immunogenicity of JNJ-64179375

    Time frame: 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.

  12. Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-64179375 in presence of 4-factor prothrombin complex concentrate (PCC)

    Time frame: 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.

  13. 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

    Time frame: 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

  14. 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

    Time frame: 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.

  15. Part 2: Terminal Half Life [t(1/2)] of JNJ-64179375 in the presence of 4-factor PCC

    Time frame: 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).

  16. Part 2: Total Systemic Clearance (CL) of JNJ-64179375 in the presence of 4-factor PCC

    Time frame: 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.

  17. Part 2: Apparent Volume of Distribution at Terminal Phase After Intravenous Administration (Vz) of JNJ-64179375 in the presence of 4-factor PCC

    Time frame: 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.

  18. Part 2: Immunogenicity of JNJ-64179375 in the presence of 4-factor PCC

    Time frame: 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.

  19. Part 2: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability

    Time frame: Baseline to End of treatment (Day 113)

  20. Part 1 and 3: Pharmacodynamic Effect of JNJ-64179375 on Platelet Function

    Time frame: 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.

  21. Part 1 and 3: Pharmacodynamic Effect of JNJ-64179375 on Coagulation Parameters

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study title

A 3-Part First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of JNJ-64179375 in Healthy Male Subjects

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Oct 31, 2016
Registry last updated
Sep 25, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.