Clinical trial NCT00861601: Phase 2, Pharmacokinetics Study of Eltrombopag in Japanese Thrombocytopenic Subjects With Chronic Liver Disease
Official title: TPL111913, a Multi-centre, Open Label, Dose Ranging Phase II Study to Assess Efficacy, Safety and Pharmacokinetics of Eltrombopag in Japanese Thrombocytopenic Subjects With Chronic Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Diseases
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-03-13
Enrollment: 38
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Primary outcomes:
measure: Change From Baseline in Platelet Counts on Day 15
timeFrame: Baseline, Day 15
Secondary outcomes:
measure: Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline Platelet Counts as Covariate)
timeFrame: Baseline, Day 15
measure: Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline of Platelet Counts and Child-Pugh Class as Covariates)
timeFrame: Baseline, Day 15
measure: Percent Change From Baseline in Platelet Counts on Day 15
timeFrame: Baseline, Day 15
measure: Platelet Counts by Treatment Visit
timeFrame: Day 1 (Baseline), Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
measure: Platelet Counts by Post-Treatment Visit
timeFrame: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
measure: Platelet Counts at Day 22
timeFrame: Day 22
measure: Change From Baseline in Platelet Counts by Treatment Visit
timeFrame: Baseline, Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
measure: Change From Baseline in Platelet Counts by Post-Treatment Visit
timeFrame: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
measure: Percentage of Responders on Day 15
timeFrame: Day 15
measure: Percentage of Responders on Day 22
timeFrame: Day 22
measure: Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class
timeFrame: Baseline, Day 15
measure: Change From Baseline in Platelet Counts on Day 15 by Sex
timeFrame: Baseline, Day 15
measure: Change From Baseline in Platelet Counts on Day 15 by Age
timeFrame: Baseline, Day 15
measure: Log-transformed Cmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg
timeFrame: Day 14, Day 15
measure: Log-transformed Tmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg
timeFrame: Day 14, Day 15
measure: Log-transformed AUC(0-t) and AUC(0-24) on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg
timeFrame: Day 14, Day 15
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Oita
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kawaguchi T, Komori A, Seike M, Fujiyama S, Watanabe H, Tanaka M, Sakisaka S, Nakamuta M, Sasaki Y, Oketani M, Hattori T, Katsura K, Sata M. Efficacy and safety of eltrombopag in Japanese patients with chronic liver disease and thrombocytopenia: a randomized, open-label, phase II study. J Gastroenterol. 2012 Dec;47(12):1342-51. doi: 10.1007/s00535-012-0600-5. Epub 2012 Jun 8.