Phase 2, Pharmacokinetics Study of Eltrombopag in Japanese Thrombocytopenic Subjects With Chronic Liver Disease
Condition: Liver Diseases
MeSH terms: Liver Diseases
Intervention: eltrombopag 12.5 milligrams (mg) tablet; eltrombopag 25 mg tablet
Intervention description: eltrombopag 12.5 mg tablet once a day; eltrombopag 25 mg tablet once a day
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      This is an open label, multi-centre, dose ranging study to assess efficacy, safety and
      pharmacokinetics of eltrombopag in thrombocytopenic subjects with chronic liver disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject who agree to comply with protocol requirements and instructions and who
             provide signed and dated written informed consent.

          -  Male and female subjects, ≥20 years of age (at the time of informed consent) with
             chronic liver disease.

          -  Child-Pugh score <=9.

          -  A baseline platelet count <50,000/mcL.

          -  A baseline serum sodium level >130 mEq/L.

          -  Haemoglobin concentration >8 g/dL, stable for at least 4 weeks.

          -  A female is eligible to enter and participate in the study if she is of:

        Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including
        any female who:

          -  Has had a hysterectomy

          -  Has had a bilateral oophorectomy (ovariectomy)

          -  Has had a bilateral tubal ligation

          -  Is post-menopausal (demonstrate total cessation of menses for longer than one year)

        Childbearing potential, has a negative urine and/or serum pregnancy test at screening, and
        within the 24 hour period prior to the first dose of investigational product and uses one
        of the following acceptable methods of contraception:

          -  Complete abstinence from intercourse.

          -  Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.

          -  Double-barrier contraception (condom with spermicidal jelly, or diaphragm with
             spermicide).

          -  Male partner who is sterile (diagnosed by a qualified medical professional) prior to
             the female subject's study entry and is the sole sexual partner for that female.

          -  Oral contraceptive (combined).

          -  Subject has no physical limitation to ingest and retain oral medication.

        Exclusion Criteria:

          -  Subjects with known or suspected hypersensitivity, intolerance or allergy to any of
             the ingredients in eltrombopag tablets.

          -  Evidence of portal vein thrombosis on abdominal imaging (ultrasound with Doppler or
             appropriate magnetic resonance imaging/computed tomography (MRI/CT) imaging
             techniques) within 3 months before the start of the study.

          -  History of arterial or venous thrombosis (including Budd-Chiari Syndrome),

        AND ≥ two of the following risk factors:

          -  hereditary thrombophilic disorders (e.g. antithrombinIII (ATIII) deficiency, etc.)

          -  hormone replacement therapy

          -  systemic contraception therapy (containing oestrogen)

          -  smoking

          -  diabetes

          -  hypercholesterolemia

          -  medication for hypertension or cancer

          -  Human Immunodeficiency Virus (HIV) infection.

          -  History of drug/alcohol abuse or dependence within 1 year prior to screening.

          -  Any disease condition associated with current active World Health Organization (WHO)
             Grade 3 or 4 bleeding.

          -  Active infection requiring systemic antibiotic therapy.

          -  Pregnant, nursing mothers, women who may be pregnant, or women who plan to become
             pregnant during the time of study participation.

          -  Treatment with platelet transfusion within 2 weeks prior to Day 1.

          -  Treatment with interferon within 4 weeks prior to Day 1.

          -  Treatment with an investigational drug within 30 days or five half-lives (whichever is
             longer) preceding the first dose of study medication.

          -  History of platelet agglutination abnormality.

          -  History of porphyria.

          -  Subjects who are deemed unsuitable for the study by the investigator (or
             subinvestigator).