A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once-daily Oral Avatrombopag in Japanese Subjects With Chronic Liver Diseases and Thrombocytopenia

NCT02227693 | Completed Phase 2 Results

• 1 other identifier: E5501-J081-204
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 14

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.

Conditions

Thrombocytopenia Associated With Chronic Liver Disease

Keywords

Thrombocytopenia; Chronic Liver Disease

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Baseline and Visit 4 (Day 10)

Secondary Outcomes (5)

• 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)

• 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)

• 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)

• 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)

• 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)

Other Outcomes (6)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From the date of first dose of study drug up to 30 days after the last dose of the study drug, up to approximately 10 months

• Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Value (TEMAV) for Haematology

  From the date of Screening until the date of last dose of study drug plus 30 days (Approximately 10 months)

• Number of Participants With Clinically Significant Findings in Laboratory Values for Serum

  From the date of Screening until the date of last dose of study drug plus 30 days (Approximately 10 months)

Study Arms (4)

avatrombopag 20-mg

EXPERIMENTAL

20 mg avatrombopag (1 x 20 mg tablet and 2 x 20 mg matching placebo tablets) once daily on Days 1 through 5

Drug: avatrombopag

avatrombopag 40-mg

EXPERIMENTAL

40 mg avatrombopag (2 x 20 mg tablets and 1 x 20 mg matching placebo tablet) once daily on Days 1 through 5

Drug: avatrombopag

avatrombopag 60-mg

EXPERIMENTAL

60 mg avatrombopag (3 x 20 mg tablets) once daily on Days 1 through 5

Drug: avatrombopag

placebo l

PLACEBO COMPARATOR

Placebo (3 x 20-mg matching placebo tablets) once daily on Days 1 through 5

Drug: Placebo

Interventions

avatrombopag DRUG

E5501 (avatrombopag) 20-mg tablets

avatrombopag 20-mg; avatrombopag 40-mg; avatrombopag 60-mg

Placebo DRUG

Placebo matching 20-mg tablets

placebo l

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Japanese subjects greater than or equal to 20 years of age at Screening with chronic liver disease.
• Subjects who have a mean baseline platelet count of less than 50 x 10\^9/L. Platelet counts will be measured on 2 separate occasions, during the Screening Period and at Baseline, and must be performed at least one day apart with neither platelet count greater than 60 x 10\^9/L.
• Model For End-stage Liver Disease (MELD) score 24 at Screening.
• If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to Screening.
• Provide written informed consent.
• Willing and able to comply with all aspects of the protocol.

You may not qualify if:

• Any history of arterial or venous thrombosis, including partial or complete thrombosis.
• Evidence of thrombosis (partial or complete) in the main portal vein, portal vein branches, or any part of the splenic mesenteric system at Screening.
• Portal vein blood flow velocity rate less than 10 cm/second at Screening.
• Hepatic encephalopathy that cannot be effectively treated.
• Subjects with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification C or D.
• Platelet transfusion or receipt of blood products containing platelets within 7 days of Screening. However packed red blood cells are permitted.
• Heparin, warfarin, nonsteroidal anti-inflammatory drugs (NSAID), aspirin, verapamil, and antiplatelet therapy with ticlopidine or glycoprotein IIb/IIIa antagonists (eg, tirofiban) within 7 days of Screening.
• Use of erythropoietin stimulating agents within 7 days of Screening.
• Interferon (IFN) use within 14 days of Screening.
• Estrogen-containing hormonal contraceptive or hormone replacement therapy use within 30 days of Screening.
• Active infection requiring systemic antibiotic therapy within 7 days of Screening. However, prophylactic use of antibiotics is permitted.
• Alcohol abuse, alcohol dependence syndrome, drug abuse, or drug dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) or acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start.
• Known to be human immunodeficiency virus positive.
• Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system).
• Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome).

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (14)

Unknown Facility

Matsuyama, Ehime, Japan

Location

Unknown Facility

Iizuka, Fukuoka, Japan

Location

Unknown Facility

Kitakyushu, Fukuoka, Japan

Location

Unknown Facility

Kurume, Fukuoka, Japan

Location

Unknown Facility

Kure, Hiroshima, Japan

Location

Unknown Facility

Sapporo, Hokkaido, Japan

Location

Unknown Facility

Sagamihara, Kanagawa, Japan

Location

Unknown Facility

Ikeda, Osaka, Japan

Location

Unknown Facility

Takatsuki, Osaka, Japan

Location

Unknown Facility

Minato-Ku, Tokyo, Japan

Location

Unknown Facility

Fukuoka, Japan

Location

Unknown Facility

Kumamoto, Japan

Location

Unknown Facility

Osaka, Japan

Location

Unknown Facility

Yamanashi, Japan

Location

Related Publications (1)

• Eguchi Y, Takahashi H, Mappa S, Santagostino E. Phase 2 study of avatrombopag in Japanese patients with chronic liver disease and thrombocytopenia. Hepatol Res. 2022 Apr;52(4):371-380. doi: 10.1111/hepr.13755. Epub 2022 Feb 21.

  PMID: 35134259 DERIVED

MeSH Terms

Conditions

Thrombocytopenia

Interventions

avatrombopag

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai Inc.

esi_medinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: August 28, 2014
• Study Start: July 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: February 28, 2019
• Results First Posted: February 28, 2019

Record last verified: 2017-12

Locations

JP (14)