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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02227693
• Date of registration: 26/08/2014
• Prospective Registration: No
• Primary sponsor: Eisai Co., Ltd.
• Public title: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once-daily Oral Avatrombopag in Japanese Subjects With Chronic Liver Diseases and Thrombocytopenia
• Scientific title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once-daily Oral Avatrombopag in Japanese Subjects With Chronic Liver Disease and Thrombocytopenia
• Date of first enrolment: July 2014
• Target sample size: 39
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02227693
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Japan

Key inclusion & exclusion criteria

Inclusion Criteria

1. Japanese subjects greater than or equal to 20 years of age at Screening with chronic
liver disease.

2. 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.

3. Model For End-stage Liver Disease (MELD) score 24 at Screening.

4. If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be
stable for 7 days prior to Screening.

5. Provide written informed consent.

6. Willing and able to comply with all aspects of the protocol.

Exclusion Criteria

1. Any history of arterial or venous thrombosis, including partial or complete
thrombosis.

2. Evidence of thrombosis (partial or complete) in the main portal vein, portal vein
branches, or any part of the splenic mesenteric system at Screening.

3. Portal vein blood flow velocity rate less than 10 cm/second at Screening.

4. Hepatic encephalopathy that cannot be effectively treated.

5. Subjects with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification C
or D.

6. Platelet transfusion or receipt of blood products containing platelets within 7 days
of Screening. However packed red blood cells are permitted.

7. 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.

8. Use of erythropoietin stimulating agents within 7 days of Screening.

9. Interferon (IFN) use within 14 days of Screening.

10. Estrogen-containing hormonal contraceptive or hormone replacement therapy use within
30 days of Screening.

11. Active infection requiring systemic antibiotic therapy within 7 days of Screening.
However, prophylactic use of antibiotics is permitted.

12. 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.

13. Known to be human immunodeficiency virus positive.

14. Any clinically significant acute or active bleeding (eg, gastrointestinal, central
nervous system).

15. Known history of any primary hematologic disorder (eg, immune thrombocytopenic
purpura, myelodysplastic syndrome).

16. Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden;
prothrombin G20210A; ATIII deficiency etc.)

17. Subjects with a history of significant cardiovascular disease (eg, congestive heart
failure New York Heart Association Grade III/IV, arrhythmia known to increase the risk
of thromboembolic events [eg, atrial fibrillation], coronary artery stent placement,
angioplasty, and coronary artery bypass grafting).

18. Females of childbearing potential who have had unprotected sexual intercourse within
30 days before study entry and who do not agree to use a highly effective method of
contraception (eg, total abstinence, an intrauterine device, a double-barrier method
[such as condom plus diaphragm with spermicide], a progesterone only contraceptive
implant/injection, or have a vasectomized partner with confirmed azoospermia)
throughout the entire study period and for 30 days after study drug discontinuation.
If currently abstinent, the subject must agree to use a double barrier method as
described above if she becomes sexually active during the study period or for 30 days
after study drug discontinuation. All females will be considered to be of childbearing
potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in
the appropriate age group and without other known or suspected cause) or have been
sterilized surgically (ie, bilateral tubal ligation, hysterectomy, or bilateral
oophorectomy) at least 1 month before dosing.

19. Females who are lactating or pregnant at Screening or Baseline (as documented by a
positive serum beta-human chorionic gonadotropin [B-hCG] test with a minimum
sensitivity 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is
required if a negative screening pregnancy test was obtained more than 72 hours before
the first dose of study drug.

20. Post liver transplant subjects.

21. Any subject who has previously received avatrombopag.

22. Hypersensitivity to avatrombopag maleate or any of its excipients.

23. Hemoglobin levels less than or equal to 8.0 or greater than or equal to 16.0 g/dL at
Screening.

24. White blood cell count less than or equal to 1.5 x 10^9/L or greater than or equal to
15.0 x 10^9/L at Screening.

25. Serum sodium level less than or equal to 130 milliequivalents/L at Screening.

26. Current malignancy including solid tumors and hematologic malignancies (except HCC).

27. Any history of a medical condition or a concomitant medical condition that, in the
opinion of the investigator(s), would compromise the subject's ability to safely
complete the study.

28. Currently enrolled in another clinical trial or used any investigational drug or
device within 30 days of Screening.



Age minimum: 20 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Thrombocytopenia Associated With Chronic Liver Disease

Intervention(s)

Drug: Placebo

Drug: avatrombopag

Primary Outcome(s)

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 [Time Frame: Baseline and Visit 4 (Day 10)]

Secondary Outcome(s)

Percentage of Participants With Platelet Count Greater Than or Equal to 75 x 10^9/L at Each Visit [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 50 x 10^9/L at Each Visit [Time Frame: 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 [Time Frame: Baseline, Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35)]

Secondary ID(s)

E5501-J081-204

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/02/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02227693