Phase 2, Pharmacokinetics Study of Eltrombopag in Japanese Thrombocytopenic Subjects With Chronic Liver Disease

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Liver Diseases

Treatments: Drug: eltrombopag 25 mg tablet; Drug: eltrombopag 12.5 milligrams (mg) tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT00861601

111913

Details and patient eligibility

About

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.

Enrollment: 38 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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38 participants in 3 patient groups

low dose

Experimental group

Description:

eltrombopag 12.5 mg/day

Treatment:

Drug: eltrombopag 12.5 milligrams (mg) tablet

middle dose

Experimental group

Description:

eltrombopag 25 mg/day

Treatment:

Drug: eltrombopag 25 mg tablet

high dose

Experimental group

Description:

eltrombopag 37.5 mg/day

Treatment:

Drug: eltrombopag 12.5 milligrams (mg) tablet

Drug: eltrombopag 25 mg tablet