Study to Assess Pharmacokinetic Drug-Drug Interaction Between Avatrombopag When Co-Administered With Fluconazole, Itraconazole, or Rifampin in Healthy Subjects

NCT ID: NCT02809768

Last Updated: 2017-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2016-09-30

Brief Summary

The purpose of this study is to determine the effects of concomitant administration with fluconazole, itraconazole, and rifampin on the pharmacokinetics (PK) of a single 20-mg dose of avatrombopag in healthy participants.

Detailed Description

This study will be a single center, open-label, drug-drug interaction study in healthy participants. The study will consist of 3 parts: In Part A, the effects of steady-state dosing of a moderate inhibitor of CYP2C9 and CYP3A (fluconazole) on the single-dose PK of avatrombopag will be assessed. In Part B, the effects of steady-state dosing of a strong CYP3A inhibitor (itraconazole) on the single-dose PK of avatrombopag will be assessed. In Part C, the effects of steady-state dosing of a strong CYP3A and moderate CYP2C9 inducer (rifampin) on the single-dose PK of avatrombopag will be assessed.

Each Part of the study will consist of 2 phases: Pretreatment and Treatment. The Pretreatment Phase will consist of 2 periods: Screening and Baseline Period 1.The Treatment Phase will consist of 2 treatment periods: Treatment Period 1 (administration of a single oral dose of avatrombopag 20 mg alone under fed conditions); and Treatment Period 2 (administration of oral doses of each inhibitor or inducer alone and concomitant administration of a single oral dose of avatrombopag 20 mg with each inhibitor or inducer [fluconazole in Part A, itraconazole in Part B, or rifampin in Part C] under fed conditions).

Conditions

Healthy Participants

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Avatrombopag plus fluconazole

Part A: Participants will be administered a single oral dose of avatrombopag (20-mg) on Day 1 of Treatment Period 1. In Treatment Period 2, fluconazole (400-mg) will be administered once daily on Days 1 to 16, and a single dose of avatrombopag (20-mg) on Day 7 in Treatment Period 2. Each dose of avatrombopag will be administered under fed conditions 30 minutes after the start of a meal.

Group Type: EXPERIMENTAL

Avatrombopag

Intervention Type: DRUG

Fluconazole

Intervention Type: DRUG

Avatrombopag plus itraconazole

Part B: Participants will be administered a single oral dose of avatrombopag (20-mg) on Day 1 of Treatment Period 1. In Treatment Period 2, itraconazole (200-mg) will be administered twice daily on Day 1 and 200-mg once daily on Days 2 to 16. A single dose of avatrombopag (20-mg) will be administered on Day 7 of Treatment Period 2. Each dose of avatrombopag will be administered under fed conditions 30 minutes after the start of a meal.

Group Type: EXPERIMENTAL

Avatrombopag

Intervention Type: DRUG

Itraconazole

Intervention Type: DRUG

Avatrombopag plus rifampin

Part C: Participants will be administered a single oral dose of avatrombopag (20-mg) on Day 1 of Treatment Period 1. In Treatment Period 2, rifampin (600-mg) will be administered once daily on Days 1 to 16. In order to avoid a food-effect on rifampin absorption, each dose will be administered 1 hour before participants consume a meal. On Day 7 of Treatment Period 2, rifampin (600-mg) and avatrombopag (20-mg) will be administered 1 hour before meal and 30 minutes after starting meal consumption.

Group Type: EXPERIMENTAL

Avatrombopag

Intervention Type: DRUG

Rifampin

Intervention Type: DRUG

Interventions

Avatrombopag

Intervention Type: DRUG

Fluconazole

Intervention Type: DRUG

Itraconazole

Intervention Type: DRUG

Rifampin

Intervention Type: DRUG

Other Intervention Names

E5501

Eligibility Criteria

Inclusion Criteria

1. Platelet count between the lower limit of normal and 300 × 10^9/L, inclusive, at Screening and each Baseline.

2. Non-smoking, male or female, age ≥18 years and ≤55 years old.

3. Body mass index (BMI) >18 and ≤32 kg/m^2 at Screening.

4. Females must not be pregnant at Screening as documented by a negative serum beta human chorionic gonadotropin (β-hCG) test with a minimum sensitivity 25 IU/L or equivalent units of β-hCG or at Baseline as documented by a negative urine pregnancy test result.

Exclusion Criteria

1. Failure to discontinue use of agents associated with higher risk of thrombosis (including estrogen containing oral contraceptives) within at least 30 days before dosing.

2. Evidence of organ dysfunction or any clinically significant deviation from normal in their medical history (e.g., history of splenectomy); history of arterial or venous thrombosis, including partial or complete thromboses (e.g., stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, pulmonary embolism); known family history of hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency).

3. Hemoglobin less than lower limit of normal at Screening and Baseline Period 1.

4. Liver functions tests (alanine transaminase [ALT], aspartate transaminase [AST], or total bilirubin) greater than the upper limit of normal Screening and Baseline Period 1.

5. Any history of gastrointestinal surgery that may affect the pharmacokinetics (PK) profiles of avatrombopag (e.g., hepatectomy, nephrectomy, cholecystectomy or digestive organ resection) at Screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eisai Medical Information

Role: STUDY_DIRECTOR

Eisai Inc.

Locations

San Antonio, Texas, United States

Countries

United States

Other Identifiers

E5501-A001-019

Identifier Type: -

Identifier Source: org_study_id