A Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of Ibrutinib in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to assess the potential effects of ketoconazole on the pharmacokinetics of ibrutinib in healthy participants.

Detailed Description
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This is a single-center, open-label (all people know the identity of the intervention), sequential design study in healthy men. All participants will receive ibrutinib on Day 1 and ibrutinib in combination with ketoconazole on Day 7. Food will be restricted from the evening before dosing until 4 hours after dosing on Days 1 and 7. Following an overnight fast, ketoconazole will be given on Days 4 to 6, 1 hour prior to ibrutinib dosing on Day 7, and again on Days 8 and 9. All ibrutinib and ketoconazole doses will be administered with water. The participants will leave the study center on Day 10.

Official Title
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An Open-Label, Sequential Design Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of Ibrutinib in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Ibrutinib
* Drug: Ketoconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) between 18 and 30 kg/m2, and body weight not less than 50 kg Blood pressure between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic Non-smoker Must agree to use an adequate contraception method during the study and minimally 3 months after the last dose of ibrutinib, and to not donate sperm during the study and for 3 months after receiving the last dose of study drug Signed an informed consent document Exclusion Criteria: History of or current clinically significant medical illness Clinically significant abnormal physical examination, vital signs or electrocardiogram (ECG) Clinically significant abnormal values for laboratorial tests Use of any prescription or nonprescription medication, except for acetaminophen, within 3 days before the first dose of the study drug is schedule History of, or a reason to believe a participant has a history of drug or alcohol abuse within the past 2 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibrutinib and Ketoconazole<br> | Drug: Ibrutinib<br>* A single oral dose of 120 mg ibrutinib (3 x 40 mg capsules) on Day 1, and 40 mg (1x 40 mg capsule) ibrutinib on Day 7.<br>Drug: Ketoconazole<br>* Ketoconazole (400 mg [2 x 200 mg] once daily) will be orally administered on Days 4, 5, 6, 7, 8 and 9.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ibrutinib plasma concentrations after administration on Day 1 |  | over 72 hours after dosing on Day 1 | 
| Ibrutinib plasma concentrations after administration on Day 7 |  | over 72 hours after dosing on Day 7 | 
| Metabolite PCI-45227 plasma concentrations after administration on Day 1 |  | over 72 hours after dosing on Day 1 | 
| Metabolite PCI-45227 plasma concentrations after administration on Day 7 |  | over 72 hours after dosing on Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ibrutinib urine concentrations after administration on Day 1 |  | over 72 hours after dosing on Day 1 | 
| Ibrutinib urine concentrations after administration on Day 7 |  | over 72 hours after dosing on Day 7 | 
| Metabolite PCI-45227 urine concentrations after administration on Day 1 |  | over 72 hours after dosing on Day 1 | 
| Metabolite PCI-45227 urine concentrations after administration on Day 7 |  | over 72 hours after dosing on Day 7 | 
| Incidence of adverse events as a measure of safety and tolerability |  | Approximately 41 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy, Ketoconazole, Ibrutinib