A Five-Treatment-Period Study to Evaluate the Single-Dose Pharmacokinetics and Pharmacodynamics of Avatrombopag in Healthy Japanese and White Subjects

Thrombocytopenia Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02039076
• Other study ID #: E5501-A001-018
• Status: Completed
• Phase: Phase 1
• First received: January 13, 2014
• Last updated: December 16, 2014
• Start date: December 2013
• Est. completion date: September 2014

Study information

• Verified date: November 2014
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: September 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 55 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Thrombocytopenia
• Thrombocytosis

Intervention

Drug:
• avatrombopag

Locations

Country	Name	City	State
United States	Parexel International Early Development Clinical Units	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) profiles of avatrombopag	The following PK parameters will be estimated for plasma: Cmax, AUC, and t1/2.	Up to 23 Weeks	No
Secondary	Pharmacodynamic (PD) profiles of avatrombopag	Analyses will carried out for AUEC(0-28d) and Emax using a mixed linear model including fixed terms for dose, race, food, sequence, and period with interaction terms for food by race and for dose by race and subject as random effect.	Up to 23 Weeks	No
Secondary	Comparison of PK and PD for avatrombopag	To assess the similarity of the PK and PD of avatrombopag between healthy Japanese and white subjects after a single administration of avatrombopag under fasted conditions	Up to 23 Weeks	No
Secondary	Adverse events (AEs ) as a measure of safety and tolerability	Saftey assessments include AEs, clinical laboratory results, vital signs, and ECGs.	Up to 23 Weeks	Yes
Secondary	Laboratory assessments as a measure of safety and tolerability	Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and other screening tests	Up to 23 Weeks	No
Secondary	Vital signs as a measure of safety and tolerability	Vital sign measurements will include systolic and diastolic blood pressure (BP) and pulse rate	Up to 23 Weeks	No
Secondary	Electrocardiogram (ECG) as a measure of safety and tolerability	Twelve-lead ECGs will be obtained as a measure of safety and tolerability	Up to 23 Weeks	No