Clinical trial NCT02039076: A Five-Treatment-Period Study to Evaluate the Single-Dose Pharmacokinetics and Pharmacodynamics of Avatrombopag in Healthy Japanese and White Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Thrombocytopenia
Keywords: Healthy
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2014-01-17
Enrollment: 48
Sex: ALL
Minimum age (years): 20
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, 5-treatment-period study to evaluate the PK and PD of avatrombopag following a single administration of avatrombopag in the fed and fasted condition, or the fed condition, to healthy Japanese and white subjects. A standard high-fat, high calorie breakfast will be used to assess the fed condition.

Detailed description: The study will comprise a Prerandomization Phase and a Randomization Phase. The Prerandomization Phase will include 2 periods, Screening and Baseline 1. The Screening Period will be up to 3 weeks (21 days) in duration. The Randomization Phase will consist of 5 single-dose treatment periods, of which 3 will include administration of avatrombopag in the fed condition and 2 will include administration of avatrombopag in the fasted condition. Each treatment period will be separated by a wash out interval of at least 28 days. Before each treatment period, subjects will complete a baseline period (Baseline Periods 2, 3, 4, and 5), during which baseline assessments will be collected. A Final Visit will occur 28 days (+/- 1 day) after dosing in Treatment Period 5.

Eligibility criteria: Inclusion Criteria

1. Platelet count between the lower limit of normal and 350 x 109/L, inclusive, at Screening and each Baseline; measurements can repeated for verification, if necessary
2. Nonsmoking, healthy white and Japanese adult male and female subjects, greater than or equal to 20 years and less than or equal to 55 years old at the time of informed consent. (Nonsmokers are defined as those who have discontinued smoking for at least 4 weeks before dosing.)
3. Japanese subjects must be born in Japan of Japanese parents and Japanese grandparents, must have lived no more than 5 years outside of Japan, and must not have changed their lifestyle or habits, including diet, while living outside of Japan.
4. Body mass index greater than or equal to 18 and less than or equal to 28 kg/m2 at Screening and Baseline Period 1. The BMI in white subjects must be within +/- 2 kg/m2 of the BMI in Japanese subjects.
5. Nonsmoking, healthy white and Japanese adult males and females between the ages of 20 and 55, inclusive
6. BMI between 18 and 28. inclusive
7. Females must not be pregnant or lactating, and if they are of childbearing potential they must agree to use a highly effective method of contraception or abstain
8. Males must have a vasectomy or they and their partner must use a highly effective method of contraception

Exclusion Criteria

1. Evidence of organ dysfunction or any clinically significant deviation from normal in their medical history (eg, history of splenectomy); history of arterial or venous thrombosis, including partial or complete thromboses (eg, stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, pulmonary embolism); known family history of hereditary thrombophilic disorders (eg, Factor V Leiden, antithrombin III deficiency)
2. Recent clinically significant illness or infection that requires medical treatment
3. Evidence of disease that may influence the outcome of the study (eg, psychiatric disorders, disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system), or subjects who have a congenital abnormality in metabolism
4. Any history of gastrointestinal surgery (eg, hepatectomy, nephrotomy, digestive organ resection)
5. Any clinically abnormal symptom or organ impairment found by medical history, physical examination, vital sign electrocardiogram (ECG) assessment, or laboratory test results
6. A known or suspected history of drug or alcohol dependency or abuse or a positive urine drug, cotinine, or alcohol test
7. Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody at Screening
8. Weight loss or gain of \>10% within 4 weeks before dosing
9. Known history of clinically significant drug or food allergy
10. Currently enrolled in another clinical trial

Primary outcomes:
measure: Pharmacokinetic (PK) profiles of avatrombopag
timeFrame: Up to 23 Weeks
Secondary outcomes:
measure: Pharmacodynamic (PD) profiles of avatrombopag
timeFrame: Up to 23 Weeks
measure: Comparison of PK and PD for avatrombopag
timeFrame: Up to 23 Weeks
measure: Adverse events (AEs ) as a measure of safety and tolerability
timeFrame: Up to 23 Weeks
measure: Laboratory assessments as a measure of safety and tolerability
timeFrame: Up to 23 Weeks
measure: Vital signs as a measure of safety and tolerability
timeFrame: Up to 23 Weeks
measure: Electrocardiogram (ECG) as a measure of safety and tolerability
timeFrame: Up to 23 Weeks
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Parexel International Early Development Clinical Units
state: California
Study officials:
References: