Drug to Drug Interaction Study of KBP-5074 in Healthy Subjects

Study Overview
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Brief Summary
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Open-label, parallel, 2-arm, fixed-sequence study to investigate the effect of coadministration of a CYP3A4 inhibitor (Cohort 1, itraconazole multiple dose) and CYP3A4 inducer (Cohort 2, rifampin multiple dose) on the plasma PK of a single dose of KBP-5074 in healthy male and female subjects.

Official Title
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Phase 1, Open-label, Parallel, 2-arm, Fixed-sequence Study to Investigate the Effect of Coadministration of CYP3A4 Inhibitor and CYP3A4 Inducer on the Pharmacokinetics, Safety, and Tolerability of KBP-5074 in Healthy Subjects

Conditions
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Healthy, Drug Drug Interaction

Intervention / Treatment
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* Drug: Itraconazole
* Drug: Rifampin
* Drug: KBP-5074


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, of any race, between 18 and 60 years of age, inclusive, at screening. Body mass index between 18.0 and 32.0 kg/m2, inclusive, at screening. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations Exclusion Criteria: Significant history or clinical manifestation of any medical history, as determined by the investigator not appropriate to participate in this study. Use of any drugs or substances known to be strong or moderate inhibitors or inducers of CYP3A4 within 30 days prior to study drug administration. Medications will be reviewed by the medical monitor to determine acceptability for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Effects of CYP3A4 inhibition on KBP-5074)<br> | Drug: Itraconazole<br>* 200 mg itraconazole, given orally as 20 mL × 10-mg/mL solution BID on Day 15, followed by QD dosing on Days 16 through 23, inclusive.<br>Drug: KBP-5074<br>* 0.5 mg KBP-5074, given orally as 1 × 0.5-mg tablet on Days 1 and 19 or Days 1 and 21<br>|
| Experimental: Cohort 2 (Effects of CYP3A4 induction on KBP-5074)<br> | Drug: Rifampin<br>* 600 mg rifampin, given orally as 2 × 300-mg capsules QD on Days 15 through 25, inclusive.<br>Drug: KBP-5074<br>* 0.5 mg KBP-5074, given orally as 1 × 0.5-mg tablet on Days 1 and 19 or Days 1 and 21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameter: Maximum observed concentration (Cmax) | Maximum observed concentration (Cmax) - Plasma | Days 1 and 19 at predose (Cohort 1) and Days 1 and 21 at predose (Cohort 2) and at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 240 hours postdose. | 
| Pharmacokinetic Parameter: Area under the concentration-time curve from time 0 to infinity (AUC0-∞) | Area under the concentration-time curve from time 0 to infinity (AUC0-∞) - Plasma | Days 1 and 19 at predose (Cohort 1) and Days 1 and 21 at predose (Cohort 2) and at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 240 hours postdose. | 
| Pharmacokinetic Parameter: Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUC0-tlast) | Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUC0-tlast) - Plasma | Days 1 and 19 at predose (Cohort 1) and Days 1 and 21 at predose (Cohort 2) and at 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 240 hours postdose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KBP5074, Healthy Subjects, itraconazole, rifampin