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

Eisai Inc.48 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Participants

Interventions

AvatrombopagDRUG

FluconazoleDRUG

ItraconazoleDRUG

RifampinDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Unnamed facility

San Antonio, Texas, United States

Outcomes

Primary Outcomes

Mean maximum observed concentration (Cmax)

Time frame: Predose of Day 1 (Treatment Period 1), Predose of Day 7 (Treatment Period 2), and 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, 96, 144, and 216 hours postdose of avatromobag for Treatment period 1 and 2

Median time at which the highest drug concentration occurs (tmax)

Mean area under the concentration-time curve from zero time to time of last quantifiable concentration AUC(0-t)

Mean area under the concentration-time curve from zero time to 72 hours postdose AUC(0-72h)

Mean terminal elimination phase half-life (t1/2)

Mean apparent total clearance following oral administration (CL/F)

Mean apparent volume of distribution at terminal phase (Vz/F)

Data from ClinicalTrials.gov

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