Clinical trial NCT01327872: Subject Variability in Two Lots of E5501 Administered to Fed and Fasted Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Purpura, Thrombocytopenic, Idiopathic
Acute Idiopathic Thrombocytopenic Purpura
Chronic Thrombocytopenia
Keywords: Idiopathic Thrombocytopenia Purpura(ITP)
Acute and Chronic Thrombocytopenia Associated with Chronic Liver Disease
TLD
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-04
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Area under the plasma concentration-time course profile (AUC) and maximum observed plasma concentration (Cmax) under fasted and fed conditions
timeFrame: 8 weeks
Secondary outcomes:
measure: 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
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Zuidlaren
country: Netherlands
facility: PRA Early Development Services
Study officials:
affiliation: Eisai Inc.
name: Franklin Johnson
role: STUDY_DIRECTOR
References: