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

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ClinicalTrials.gov Identifier: NCT02230033
Recruitment Status : Completed
First Posted : September 3, 2014
Last Update Posted : October 20, 2016
Sponsor:
Information provided by (Responsible Party):
Aragon Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: JNJ-56021927 Drug: Itraconazole Drug: Gemfibrozil Phase 1

Detailed Description:
This is a single-dose, single-center, open-label (all people know the identity of the intervention), 3-treatment, randomized (study medication assigned to participants by chance) and parallel-group (a medical research study comparing the response in two or more groups of participants receiving different interventions [treatments]) study. The study consists of Screening Phase (that is, 21 days before study commences on Day 1); open-label treatment Phase and end-of-study or early withdrawal assessment. All participants will be randomly assigned to 1 of 3 treatments, that is, Treatment A (single dose of JNJ-56021927 on Day 1), Treatment B (200 milligram [mg] itraconazole once daily from Day 1 up to Day 32 along with single dose of JNJ-56021927 on Day 4), and Treatment C (600 mg gemfibrozil twice daily from Day 1 up to Day 32 along with single dose of JNJ-56021927 on Day 4). Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. The maximum duration of participation in the study per participant will be approximately 78 days (Treatment A) or 81 days (Treatment B and C). Participants' safety will be monitored throughout the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, Parallel-Group Drug-Drug Interaction Study to Assess the Effect of Multiple Doses of Itraconazole or Gemfibrozil on the Pharmacokinetics of a Single Dose of JNJ-56021927 in Healthy Male Subjects
Study Start Date : September 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Experimental: Treatment A
Single oral dose of JNJ-56021927 240 milligram (mg) capsule will be administered on Day 1.
Drug: JNJ-56021927
Single oral dose of JNJ-56021927 240 milligram (mg) capsule will be administered on Day 1 or Day 4 in any of the treatment.

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

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

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

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




Primary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  2. Time to Reach Maximum Concentration (tmax) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  3. Area Under the Plasma Concentration-Time Curve From Time Zero to 672 Hours (AUC [0-672]) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  4. Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  5. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  6. Percentage of Extrapolated AUC (0-infinity) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  7. Elimination Half-Life (t [1/2] Lambda) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  8. Rate Constant (Lambda[z]) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  9. Time to last quantifiable plasma concentration (tlast) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  10. Total Plasma Clearance (CL/F) of JNJ-56021927 [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  11. Metabolite to Parent Drug Ratio for maximum observed plasma concentration (MPR Cmax) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  12. Metabolite to Parent Drug Ratio for AUC (0 to last) (MPR AUC [0-last]) [ Time Frame: Up to Day 57 or Day 60 ]
    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).

  13. Metabolite to Parent Drug Ratio for AUC (0-infinity) (MPR AUC [0-infinity]) [ Time Frame: Up to Day 57 or Day 60 ]
    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).


Secondary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Screening up to Day 57 for treatment A or up to Day 60 for treatment B or C or early withdrawal ]
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to day 57 for treatment A or up to day 60 for treatment B or C, that are absent before treatment or that worsened relative to pretreatment state.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02230033


Locations
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United States, Arizona
Tempe, Arizona, United States
Sponsors and Collaborators
Aragon Pharmaceuticals, Inc.
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

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Responsible Party: Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02230033     History of Changes
Other Study ID Numbers: CR105398
56021927PCR1012 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: September 3, 2014    Key Record Dates
Last Update Posted: October 20, 2016
Last Verified: October 2016

Keywords provided by Aragon Pharmaceuticals, Inc.:
JNJ-56021927
Itraconazole
Gemfibrozil

Additional relevant MeSH terms:
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Itraconazole
Hydroxyitraconazole
Gemfibrozil
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Cytochrome P-450 CYP2C8 Inhibitors