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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01327872
First received: March 30, 2011
Last updated: March 8, 2012
Last verified: March 2012
  Purpose

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%.


Condition Intervention Phase
Purpura, Thrombocytopenic, Idiopathic
Acute Idiopathic Thrombocytopenic Purpura
Chronic Thrombocytopenia
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
Drug: E5501 40 mg 2 x 20-mg tablets, orally, with food
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Area under the plasma concentration-time course profile (AUC) and maximum observed plasma concentration (Cmax) under fasted and fed conditions [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 84
Study Start Date: February 2011
Study Completion Date: June 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A 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
Experimental: Treatment B Drug: 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
Experimental: Treatment C Drug: 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
Experimental: Treatment D Drug: 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

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).

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01327872

Locations
Netherlands
PRA Early Development Services
Zuidlaren, Netherlands
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Franklin Johnson Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01327872     History of Changes
Other Study ID Numbers: E5501-G000-010
Study First Received: March 30, 2011
Last Updated: March 8, 2012
Health Authority: Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Eisai Inc.:
Idiopathic Thrombocytopenia Purpura(ITP)
Acute and Chronic Thrombocytopenia Associated with Chronic Liver Disease
TLD

Additional relevant MeSH terms:
Thrombocytopenia
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Blood Coagulation Disorders
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases

ClinicalTrials.gov processed this record on September 18, 2014