Subject Variability in Two Lots of E5501 Administered to Fed and Fasted Healthy Subjects

Eisai Inc.84 enrolled

Overview

This will be a randomized, open-label, four-group, two-period, replicate design study to evaluate the effect of food on within and between subject variability in second generation formulation 20-mg tablet strengths, Lots P01008ZZA and P01009ZZA, administered as single doses of 40mg to 84 healthy male and female subjects. The study is powered to detect both a reduction in either the within or between subject variability (coefficient of variation \[CV\]%) of approximately 35%.

This is a Phase 2, multi-center, double-blind, randomized, placebo-controlled, dose-ranging, parallel-group study. The PK and PK/PD relationship of AKR-501 will also be studied. Approximately 65 eligible patients will be randomized in a 3:3:3:3:1 ratio in a double-blinded fashion into one of five parallel treatment groups to receive daily doses of either AKR-501 2.5, 5, 10 or 20 mg or placebo for 28 days, respectively. Each AKR-501 dosing group will consist of 15 patients while the placebo group will consist of 5 patients. All study patients will be evaluated weekly (Days 3, 5, 7, 14, 21 and 28) for safety, efficacy, and (Days 7, 14, 21, and 28) AKR-501 pharmacokinetics while receiving study treatment with a final assessment for safety and effectiveness to be done 2 weeks after the last study dose (Day 42).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

E5501 40 mg 2 x 20-mg tablets, orally, fastedDRUG

single 40 mg dose (2 x 20-mg tablets) of Lot P01008ZZA in the fasted condition

E5501 40 mg 2 x 20-mg tablets, orally, with foodDRUG

single 40 mg dose (2 x 20-mg tablets) of Lot P01008ZZA in the fed condition

E5501 40mg 2 x 20-mg tablets, orally, fastedDRUG

single 40 mg dose (2 x 20-mg tablets) of Lot P01009ZZA in the fasted condition

E5501 40 mg 2 x 20-mg tablets, orally, with foodDRUG

single 40 mg dose (2 x 20-mg tablets) of Lot P01009ZZA in the fed condition

Eligibility

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

Medical Language ↔ Plain English

Inclusion criteria: * Normal healthy male or female subjects age greater than or equal to 18 years and less than or equal to 55 years * Body mass index greater than or equal to 18 and less than or equal to 32kg/m2 at Screening * Platelet count greater than or equal to 120x109/L and less than or equal to 250x109/L * Women of childbearing potential must agree to use a highly effective method of contraception, other than estrogen-based hormonal contraceptives, during the Randomization Phase of the study Exclusion Criteria: * Evidence of clinically significant cardiovascular, hepatic, gastrointestinal, renal, respiratory, endocrine, hematologic, neurologic, or psychiatric disease or abnormalities or a known history of any gastrointestinal surgery that could impact PK of the study drug * Agents associated with thrombotic events (including oral contraceptives) must be discontinued within 30 days of first study drug administration * Evidence of organ dysfunction or any clinically significant deviation from normal in their medical history, e.g., history of splenectomy * History of venous or arterial thrombotic disease or other hypercoaguable state * Hemoglobin less than lower limit of normal (LLN) levels (females 7.1 mmol/L, males 8.1 mmol/L

Outcomes

Primary Outcomes

Area under the plasma concentration-time course profile (AUC) and maximum observed plasma concentration (Cmax) under fasted and fed conditions

Time frame: 8 weeks

Secondary Outcomes

To evaluate the comparison of the overall effect of food on the bioavailability of E5501 relative to the fasted condition as measured by AUC(0-inf) and Cmax