A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once-daily Oral Avatrombopag in Japanese Subjects With Chronic Liver Diseases and Thrombocytopenia
- Conditions
- Thrombocytopenia Associated With Chronic Liver Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT02227693
- Lead Sponsor
- Eisai Co., Ltd.
- Brief Summary
This is a phase 2, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag for Japanese subjects with thrombocytopenia associated with chronic liver disease. This study will assess the effect of avatrombopag on platelet counts in Japanese subjects. Subjects will be enrolled into 2 cohorts according to the mean platelet count measured at Screening and Baseline. Within the lower baseline platelet count cohort (less than 40 x 10\^9/L), subjects will be randomized in a 1:1:1:3 ratio to receive placebo, 20 mg avatrombopag, 40 mg avatrombopag, or 60 mg avatrombopag for 5 days. Within the higher baseline platelet count cohort (from 40 to less than 50 x 10\^9/L), subjects will be randomized in a 2:1:2 ratio to receive placebo, 20 mg avatrombopag, or 40 mg avatrombopag for 5 days.
- Detailed Description
This study will consist of Prerandomization Phase and Randomization Phase. The Prerandomization Phase includes a Screening Period (Day -28 to Day -1) and a Baseline Period (Day 1). During the Prerandomization Phase, participants will be divided into two cohorts based on the platelet count: Low Platelet Count Cohort and High Platelet Count Cohort. Participants in Low Platelet Count Cohort will be randomized to receive one of the four treatments: Placebo, Avatrombopag 20 mg, Avatrombopag 40 mg, or Avatrombopag 60 mg. Participants in High Platelet Count Cohort will be randomized to receive one of the three treatments: Placebo, Avatrombopag 20 mg, or Avatrombopag 40 mg.
The Randomization Phase includes the Treatment Period and the Follow-up Period. The Follow-up Period comprises 3 visits: Visit 4 (5 to 8 days after last dose of study drug \[Study Day 10 to 13\]), Visit 5 (12 to 15 days after last dose of study drug \[Study Day 17 to 20\]), and 30 days after receiving the last dose of study drug.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description avatrombopag 60-mg avatrombopag 60 mg avatrombopag (3 x 20 mg tablets) once daily on Days 1 through 5 placebo l Placebo Placebo (3 x 20-mg matching placebo tablets) once daily on Days 1 through 5 avatrombopag 20-mg avatrombopag 20 mg avatrombopag (1 x 20 mg tablet and 2 x 20 mg matching placebo tablets) once daily on Days 1 through 5 avatrombopag 40-mg avatrombopag 40 mg avatrombopag (2 x 20 mg tablets and 1 x 20 mg matching placebo tablet) once daily on Days 1 through 5
- Primary Outcome Measures
Name Time Method Percentage of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L and at Least 20 x 10^9/L Increase From Baseline at Visit 4 Baseline and Visit 4 (Day 10) Responders were defined as participants whose platelet count was greater than or equal to 50×10\^9/liter (L) and change from baseline was at least 20×10\^9/L at Visit 4. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis. Two-sided 95% confidence interval (CI) is calculated by Clopper and Pearson method.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L at Each Visit Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35) Responders were defined as the participants whose platelet count greater than or equal to 50 x 10\^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis. Two-sided 95% CI is calculated by Clopper and Pearson method.
Percentage of Participants With Platelet Count Greater Than or Equal to 75 x 10^9/L at Each Visit Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35) Responders were defined as the participants whose platelet count greater than or equal to 75 x 10\^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis. Two-sided 95% CI is calculated by Clopper and Pearson method.
Percentage of Participants With Platelet Count Greater Than or Equal to 150 x 10^9/L At Each Visit Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35) Responders were defined as the participants whose platelet count greater than or equal to 150 x 10\^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis.
Percentage of Participants With Platelet Count Greater Than or Equal to 200 x 10^9/L At Each Visit Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35) Responders were defined as the participants whose platelet count greater than or equal to 200 x 10\^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis.
Platelet Count and Change From Baseline in Platelet Count by Visit Baseline, Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35)