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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02949206
• Other study ID #: CR108238
• Secondary ID: 64179375EDI10012
• Status: Completed
• Phase: Phase 1
• First received: October 27, 2016
• Last updated: September 22, 2017
• Start date: November 14, 2016
• Est. completion date: August 9, 2017

Study information

• Verified date: September 2017
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 9, 2017
• Est. primary completion date: August 9, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

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.
• 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).
• 4 Factor Prothrombin Complex Concentrate (PCC)
Following a single dose of JNJ-64179375, participants will receive a single IV dose of 4 factor-PCC.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability		Up to Day 113
Primary	Part 3: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability		Up to Day 113
Primary	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
Primary	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
Secondary	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
Secondary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 2: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability		Baseline to End of treatment (Day 113)
Secondary	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
Secondary	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