Study to Assess Drug-Drug Interaction Between Itraconazole or Gemfibrozil and JNJ-56021927

NCT02230033 | Completed Phase 1

• 2 other identifiers: CR10539856021927PCR1012
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effect of multiple doses of itraconazole or gemfibrozil on the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) of JNJ-56021927 and its metabolites (JNJ 56142060 and JNJ-56142021) in healthy male participants.

Conditions

Healthy

Keywords

JNJ-56021927; Itraconazole; Gemfibrozil

Outcome Measures

Primary Outcomes (13)

• Maximum Plasma Concentration (Cmax)

  The Cmax is the maximum observed plasma concentration. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Time to Reach Maximum Concentration (tmax)

  The tmax is time to reach the maximum observed plasma concentration. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Area Under the Plasma Concentration-Time Curve From Time Zero to 672 Hours (AUC [0-672])

  The AUC (0-672) is the area under the plasma concentration-time curve from time zero to 672 hours. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])

  The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])

  The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Percentage of Extrapolated AUC (0-infinity)

  The percentage of AUC (0-infinity) that is due to extrapolation from Tlast to infinity (AUC%Extrapolation) is calculated by using the formula AUC\_%extrapolation = 100\*(AUC \[0-infinity\] minus (AUC \[0-last\])/(AUC (0-infinity). Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Elimination Half-Life (t [1/2] Lambda)

  Elimination half-life (t \[1/2\] Lambda) is associated with the terminal slope (lambda \[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z). Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Rate Constant (Lambda[z])

  Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Time to last quantifiable plasma concentration (tlast)

  The tlast is the time to last observed quantifiable plasma concentration. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Total Plasma Clearance (CL/F) of JNJ-56021927

  Total plasma clearance of drug after extravascular administration, uncorrected for absolute bioavailability, calculated as Dose/AUC (0-infinity) (JNJ-56021927 only). Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Metabolite to Parent Drug Ratio for maximum observed plasma concentration (MPR Cmax)

  Metabolite to parent drug ratio for maximum observed plasma concentration will be calculated. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Metabolite to Parent Drug Ratio for AUC (0 to last) (MPR AUC [0-last])

  Metabolite to parent drug ratio for AUC (0 to last) will be calculated. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

• Metabolite to Parent Drug Ratio for AUC (0-infinity) (MPR AUC [0-infinity])

  Metabolite to parent drug ratio for AUC (0-infinity) will be calculated. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).

  Up to Day 57 or Day 60

Secondary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

  Screening up to Day 57 for treatment A or up to Day 60 for treatment B or C or early withdrawal

Study Arms (3)

Treatment A

EXPERIMENTAL

Single oral dose of JNJ-56021927 240 milligram (mg) capsule will be administered on Day 1.

Drug: JNJ-56021927

Treatment B

EXPERIMENTAL

Itraconazole 200 mg (2 capsules of 100 mg) will be administered once daily orally from Day 1 until Day 32, along with single oral dose of JNJ-56021927 240 mg capsule on Day 4.

Drug: JNJ-56021927; Drug: Itraconazole

Treatment C

EXPERIMENTAL

Gemfibrozil 600 mg oral tablet will be administered twice daily from Day 1 until Day 32, along with single oral dose of JNJ-56021927 240 mg capsule on Day 4.

Drug: JNJ-56021927; Drug: Gemfibrozil

Interventions

JNJ-56021927 DRUG

Single oral dose of JNJ-56021927 240 milligram (mg) capsule will be administered on Day 1 or Day 4 in any of the treatment.

Treatment A; Treatment B; Treatment C

Itraconazole DRUG

Itraconazole 200 mg (2 capsules of 100 mg) will be administered once daily orally from Day 1 until Day 32.

Treatment B

Gemfibrozil DRUG

Gemfibrozil 600 mg oral tablet will be administered twice daily from Day 1 until Day 32.

Treatment C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must agree to use an adequate contraception method as deemed appropriate by the Investigator and specified in protocol, always use a condom during sexual intercourse, and to not donate sperm during the study and for 3 months after receiving the study drug
• Body mass index between 18 and 30 kilogram (kg) per square meter, and body weight not less than 50 kg
• Blood pressure (supine for 5 minutes) between 90 and 140 millimeter of mercury (mm Hg) systolic, and no higher than 90 mm Hg diastolic
• A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function at Screening, including: Pulse rate between 45 and 99 beats per minute (bpm); QTc interval less than or equal to (\<=) 450 milliseconds; QRS interval of less than (\<) 120 milliseconds; PR interval \<220 milliseconds; and morphology consistent with healthy cardiac conduction and function
• Nonsmoker within the previous 2 months (calculated from first dosing)

You may not qualify if:

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results
• Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at Screening or at admission to the study center as deemed appropriate by the Investigator
• Medical history of gallbladder disease (cholecystitis, cholelithiasis, cholecystectomy)
• Presence of sexual dysfunction or any medical condition that would affect sexual function
• Screening serum testosterone level of \< 200 nanogram/deciliter (ng/dL)
• Previous history of photoallergy or phototoxic reaction during treatment with fibrates

Sponsors & Collaborators

• Aragon Pharmaceuticals, Inc.: lead

Study Sites (1)

Unknown Facility

Tempe, Arizona, United States

Location

MeSH Terms

Interventions

Itraconazole; Gemfibrozil

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Pentanoic Acids; Valerates; Phenyl Ethers; Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2014
• First Posted: September 3, 2014
• Study Start: September 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: October 20, 2016

Record last verified: 2016-10

Locations

US (1)