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

Purpura, Thrombocytopenic, Idiopathic Clinical Trial

Official title:

A Randomized, Open-Label, 4-Group, 2-Period Replicate Design Study to Evaluate Within- and Between-Subject Variability in Exposure of Two Lots of E5501 20 mg Tablets, Administered as Single Doses of 40 mg, in the Fasted and Fed Conditions to Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01327872
• Other study ID #: E5501-G000-010
• Status: Completed
• Phase: Phase 1
• First received: March 30, 2011
• Last updated: March 8, 2012
• Start date: February 2011
• Est. completion date: June 2011

Study information

• Verified date: March 2012
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medicines Evaluation Board (MEB)
• Study type: Interventional

Clinical Trial 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%.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: June 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Idiopathic Thrombocytopenic Purpura
• Chronic Thrombocytopenia
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia
• Thrombocytosis

Intervention

Drug:
• E5501 40 mg 2 x 20-mg tablets, orally, fasted
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 food
single 40 mg dose (2 x 20-mg tablets) of Lot P01008ZZA in the fed condition
• E5501 40mg 2 x 20-mg tablets, orally, fasted
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 food
single 40 mg dose (2 x 20-mg tablets) of Lot P01009ZZA in the fed condition

Locations

Country	Name	City	State
Netherlands	PRA Early Development Services	Zuidlaren

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time course profile (AUC) and maximum observed plasma concentration (Cmax) under fasted and fed conditions		8 weeks	No
Secondary	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	No