Last updated: 11/03/2018 12:23:25
Phase 2, Pharmacokinetics study of Eltrombopag in Japanese Thrombocytopenic Subjects with Chronic Liver Disease
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in Platelet Counts on Day 15
Timeframe: Baseline, Day 15
Secondary outcomes:
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
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
Percent Change from Baseline in Platelet Counts on Day 15
Timeframe: Baseline, Day 15
Platelet Counts by Treatment Visit
Timeframe: Day 1 (Baseline), Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
Platelet Counts by Post-Treatment Visit
Timeframe: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
Platelet Counts at Day 22
Timeframe: Day 22
Change from Baseline in Platelet Counts by Treatment Visit
Timeframe: Baseline, Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
Change from Baseline in Platelet Counts by Post-Treatment Visit
Timeframe: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
Percentage of Responders on Day 15
Timeframe: Day 15
Percentage of Responders on Day 22
Timeframe: Day 22
Change from Baseline in Platelet Counts on Day 15 by Child-Pugh Class
Timeframe: Baseline, Day 15
Change from Baseline in Platelet Counts on Day 15 by Sex
Timeframe: Baseline, Day 15
Change from Baseline in Platelet Counts on Day 15 by Age
Timeframe: Baseline, Day 15
Log-transformed Cmax on Days 14 and 15 in participants receiving eltrombopag 12.5 mg
Timeframe: Day 14, Day 15
Log-transformed Tmax on Days 14 and 15 in participants receiving eltrombopag 12.5 mg
Timeframe: Day 14, Day 15
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
Interventions:
Enrollment:
38
Primary completion date:
2009-21-08
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
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;
Farrell C, Hayes SC, Wire M, Zhang J.Population pharmacokinetic/pharmacodynamic modelling of eltrombopag in healthy volunteers and subjects with chronic liver disease.Br J Clin Pharmacol.2014;77(3):532-44
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;47(12):1342-1351
Medical condition
Liver Diseases
Product
eltrombopag
Collaborators
GSK
Study date(s)
January 2009 to August 2009
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
20+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion 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).
Trial location(s)
Showing 1 - 6 of 10 Results
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2009-21-08
Actual study completion date
2009-21-08
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website