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

Phase 1

Completed

• Conditions: Purpura, Thrombocytopenic, Idiopathic; Acute Idiopathic Thrombocytopenic Purpura; Chronic Thrombocytopenia
• Interventions: Drug: E5501 40 mg 2 x 20-mg tablets, orally, fasted; Drug: E5501 40 mg 2 x 20-mg tablets, orally, with food; Drug: E5501 40mg 2 x 20-mg tablets, orally, fasted

• Registration Number: NCT01327872
• Lead Sponsor: Eisai Inc.

Brief Summary

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%.

Detailed Description

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 Timeline

• Study Start: 2011-02
• Study First Submitted: 2011-03-30
• Study First Submitted QC: 2011-03-31
• Primary Completion: 2011-04
• Study First Posted: 2011-04-04
• Study Completion: 2011-06
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-08
• Last Update Posted: 2012-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment A	E5501 40 mg 2 x 20-mg tablets, orally, fasted	-
Treatment B	E5501 40 mg 2 x 20-mg tablets, orally, with food	-
Treatment C	E5501 40mg 2 x 20-mg tablets, orally, fasted	-
Treatment D	E5501 40 mg 2 x 20-mg tablets, orally, with food	-

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time course profile (AUC) and maximum observed plasma concentration (Cmax) under fasted and fed conditions	8 weeks

Secondary Outcome Measures

Name	Time	Method
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	8 weeks

Trial Locations

Locations (1)

PRA Early Development Services; 🇳🇱 Zuidlaren, Netherlands