Clinical trial NCT01251731: Single and Multiple Dose Asian Bridging Study
Official title: A Randomized, Double-Blind, Placebo-Controlled, 3-Way Crossover Study to Evaluate the Single-Dose Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of 10, 40, and 80 mg E5501 Followed by a Selected Dose for Multiple Dosing Administered to Healthy Japanese, Chinese, and Caucasian Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2010-12-02
Enrollment: 36
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the single-dose (SD) pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of 10, 40, and 80 mg E5501 followed by a selected dose for multiple dosing (MD) in healthy Japanese, Chinese, and Caucasian subjects.

Detailed description: This study will evaluate the single-dose (SD) pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of oral doses of 10, 40, and 80 mg E5501 administered to 36 healthy male and female Japanese, Chinese, and Caucasian subjects. For the SD Treatment Period, 12 subjects from each ethnic group will be randomized to receive single doses of 10, 40, or 80 mg E5501 or matching placebo each treatment period. Each subject will be allocated to a treatment sequence to be dosed with either placebo for the three periods or dosed with each of the three different doses in the three periods. For the Multiple-Dose (MD) Treatment Period the 12 subjects in each ethnic group will be further randomized as active (dose level to be determined from the SD Treatment Period or placebo in a 3:1 ratio.

Eligibility criteria: Key Inclusion Criteria:

* Normal healthy adult males and females (age 20-45 years)
* Body Mass Index greater than or equal to 18 and less than or equal to 29 at the time of screening
* Japanese and Chinese subjects must be born in their respective countries of origin and have parents and grandparents of Japanese or Chinese descent, respectively
* Japanese subjects must have lived outside of Japan for no more than 5 years; Chinese subjects must have lived outside of China for no more than 10 years
* In addition to mainland China, Chinese subjects may be from Taiwan, Hong Kong, or Mongolia
* Japanese and Chinese subjects must not have significantly changes their lifestyle with regard to diet; i.e., their diet must not have significantly changed since leaving China or Japan
* Platelet count between 150,000 and 300,000/mm3

Key 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 the PK of the study drug
* 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 hypercoagulable state
* Hemoglobin level less than 12.0 g/dL

Primary outcomes:
measure: • To compare the single-dose pharmacokinetics (PK), as measured by AUCinf of three doses of E5501 (10, 40, and 80 mg) in healthy Japanese and Chinese subjects relative to healthy Caucasian subjects
timeFrame: up to 96 hours post-dose
measure: • To compare the multiple-dose steady-state PK, as measured by AUCss, of E5501 in healthy Japanese and Chinese subjects relative to Caucasian subjects
timeFrame: up to 96 hours after dosing on Day 7 or up to 240 hours after the first drug dosing
measure: • To compare the multiple-dose pharmacodynamic (PD) response as measured by platelet counts for E5501 in healthy Japanese and Chinese subjects relative to Caucasian subjects
timeFrame: through Day 21 for each SD Treatment Period and through Day 30 for the MD Treatment Period
measure: • To compare the single-dose pharmacokinetics (PK), as measured by Cmax of three doses of E5501 (10, 40, and 80 mg) in healthy Japanese and Chinese subjects relative to healthy Caucasian subjects
timeFrame: up to 96 hours post-dose
Secondary outcomes:
measure: To evaluate single-dose linearity of 10, 40 and 80mg E5501 in healthy Japanese, Chinese, and Caucasian subjects
timeFrame: from Day 1 SD Treatment Period 1 through Day 30 MD Treatment Period 4
measure: To characterize PK/PD relationships between E5501 exposure and platelet count response in healthy Japanese, Chinese, and Caucasian subjects
timeFrame: from Day 1 SD Treatment Period 1through Day 30 MD Treatment Period 4
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Parexel International, Early Phase Clinical Unit
state: California
Study officials:
affiliation: Eisai Inc.
name: Franklin Johnson
role: STUDY_DIRECTOR
References: