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

Eisai

Status and phase: Completed; Phase 1

Conditions: Purpura, Thrombocytopenic, Idiopathic; Chronic Thrombocytopenia; Acute Idiopathic Thrombocytopenic Purpura

Treatments: Drug: E5501 40mg 2 x 20-mg tablets, orally, fasted; Drug: E5501 40 mg 2 x 20-mg tablets, orally, with food; Drug: E5501 40 mg 2 x 20-mg tablets, orally, fasted

Study type: Interventional

Funder types: Industry

Identifiers

NCT01327872

E5501-G000-010

Details and patient eligibility

About

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%.

Full 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).

Enrollment: 84 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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84 participants in 4 patient groups

Treatment A

Experimental group

Treatment:

Drug: E5501 40 mg 2 x 20-mg tablets, orally, fasted

Treatment B

Experimental group

Treatment:

Drug: E5501 40 mg 2 x 20-mg tablets, orally, with food

Drug: E5501 40 mg 2 x 20-mg tablets, orally, with food

Treatment C

Experimental group

Treatment:

Drug: E5501 40mg 2 x 20-mg tablets, orally, fasted

Treatment D

Experimental group

Treatment:

Drug: E5501 40 mg 2 x 20-mg tablets, orally, with food

Drug: E5501 40 mg 2 x 20-mg tablets, orally, with food