临床试验/NCT02809768

NCT02809768已完成1 期

A 3-Part, Open-Label Study to Assess Pharmacokinetic Drug-Drug Interaction Between Avatrombopag When Co-Administered With Fluconazole (Moderate Inhibitor of CYP2C9 and CYP3A), Itraconazole (Strong CYP3A Inhibitor), or Rifampin (Strong CYP3A and Moderate CYP2C9 Inducer) in Healthy Subjects

Eisai Inc.0 个研究点目标入组 48 人开始时间: 2016年4月最近更新: 2017年3月9日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Eisai Inc.
入组人数: 48
主要终点: Mean maximum observed concentration (Cmax)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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).

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 55 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•Platelet count between the lower limit of normal and 300 × 10^9/L, inclusive, at Screening and each Baseline.
•Non-smoking, male or female, age ≥18 years and ≤55 years old.
•Body mass index (BMI) >18 and ≤32 kg/m^2 at Screening.
•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.

排除标准

•Failure to discontinue use of agents associated with higher risk of thrombosis (including estrogen containing oral contraceptives) within at least 30 days before dosing.
•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).
•Hemoglobin less than lower limit of normal at Screening and Baseline Period
•Liver functions tests (alanine transaminase [ALT], aspartate transaminase [AST], or total bilirubin) greater than the upper limit of normal Screening and Baseline Period
•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.

研究组 & 干预措施

Avatrombopag plus fluconazole

Experimental

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.

干预措施: Avatrombopag (Drug)

Avatrombopag plus fluconazole

Experimental

干预措施: Fluconazole (Drug)

Avatrombopag plus itraconazole

Experimental

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.

干预措施: Avatrombopag (Drug)

Avatrombopag plus itraconazole

Experimental

干预措施: Itraconazole (Drug)

Avatrombopag plus rifampin

Experimental

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.

干预措施: Avatrombopag (Drug)

Avatrombopag plus rifampin

Experimental

干预措施: Rifampin (Drug)

结局指标

主要结局

Mean maximum observed concentration (Cmax)

时间窗: 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 apparent total clearance following oral administration (CL/F)

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

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 extrapolated to infinite time AUC(0-inf)

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

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

次要结局

Median observed time of maximum increase in platelet counts following avatrombopag dosing in each treatment period (TEmax)(Predose of Day 1, Days 3, 4, 5, 7, 10, 12, 14, 21, and 28 of Treatment Period 1. Predose of Day 7, Days 9, 10, 11, 13, 16, 18, 20, 27, and 34 of Treatment Period 2)
Maximum change from baseline in platelet count (ΔEmax = Emax - baseline platelet count at predose on Treatment Period 1 Day 1) (ΔEmax)(Predose of Day 1, Days 3, 4, 5, 7, 10, 12, 14, 21, and 28 of Treatment Period 1. Predose of Day 7, Days 9, 10, 11, 13, 16, 18, 20, 27, and 34 of Treatment Period 2)
Maximum percent change from baseline in platelet count (%ΔEmax = ΔEmax / baseline platelet count at predose on Period 1 Day 1 x 100) (%ΔEmax)(Predose of Day 1, Days 3, 4, 5, 7, 10, 12, 14, 21, and 28 of Treatment Period 1. Predose of Day 7, Days 9, 10, 11, 13, 16, 18, 20, 27, and 34 of Treatment Period 2)
Mean area under the effect curve for platelet count following avatrombopag dosing through 28 days after dosing (AUEC(0-28d))(Predose of Day 1, Days 3, 4, 5, 7, 10, 12, 14, 21, and 28 of Treatment Period 1. Predose of Day 7, Days 9, 10, 11, 13, 16, 18, 20, 27, and 34 of Treatment Period 2)
Percentage of participants with treatment emergent adverse events and serious adverse events(Up to approximately 3 months)
Mean maximum platelet counts following avatrombopag dosing observed in each treatment period (Emax)(Predose of Day 1, Days 3, 4, 5, 7, 10, 12, 14, 21, and 28 of Treatment Period 1. Predose of Day 7, Days 9, 10, 11, 13, 16, 18, 20, 27, and 34 of Treatment Period 2)

研究者

发起方

Eisai Inc.

申办方类型

Industry

责任方

Sponsor

相似试验

已完成

1 期

A Study to Evaluate the Effect of Fluconazole and Itraconazole on Erdafitinib Pharmacokinetics in Healthy Adult ParticipantsHealthy

NCT03135106Janssen Research & Development, LLC54

终止

2 期

Safety Study of Fluconazole in Combination With Flucytosine for the Treatment of Early Cryptococcal InfectionCryptococcal Infection Disseminated

NCT01562132Yale University6

已完成

1 期

Drug-Drug Interaction Study Between Fluconazole and EDP-938 in Healthy SubjectsRSV Infection

NCT04871724Enanta Pharmaceuticals, Inc24

已完成

1 期

A Study to Evaluate the Effect of a Dual CYP2C19 and CYP3A4 Inhibitor, Fluconazole, on the Pharmacokinetics of Fedratinib in Healthy Adult SubjectsHealthy Volunteers

NCT04702464Celgene29

已完成

3 期

Comparison of Fluconazole vs Voriconazole to Treat Fungal Infections for Blood and Marrow Transplants (BMT CTN 0101)InfectionLymphomaLeukemia

NCT00075803Medical College of Wisconsin600