Liver DiseasesPhase 2NCT00861601
Phase 2, Pharmacokinetics Study of Eltrombopag in Japanese Thrombocytopenic Subjects With Chronic Liver Disease
A Phase 2 study testing eltrombopag 12.5 milligrams (mg) tablet and eltrombopag 25 mg tablet in people with Liver Diseases, run by GlaxoSmithKline at 10 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Liver Diseases
- What is being tested?
- eltrombopag 12.5 milligrams (mg) tablet and eltrombopag 25 mg tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 10 sitesJapan
- Study dates
- Jan 2009to Aug 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 19Show fewer
- 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.
Who cannot join
- 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
Show all 22Show fewer
- 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 locations and contacts
10 sites in 1 country.
10 sites in 1 country
Japan10 sites
GSK Investigational Site
Fukuoka, 810-8563
GSK Investigational Site
Fukuoka, 814-0180
GSK Investigational Site
Fukuoka, 815-8555
GSK Investigational Site
Fukuoka, 830-0011
GSK Investigational Site
Fukuoka, 839-0863
GSK Investigational Site
Kagoshima, 890-8520
GSK Investigational Site
Kumamoto, 860-8556
GSK Investigational Site
Kumamoto, 862-8655
GSK Investigational Site
Nagasaki, 856-8562
GSK Investigational Site
Ōita, 879-5593
About this study
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
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.
- Conditions
- Liver Diseases
- Being tested
- eltrombopag 12.5 milligrams (mg) tablet, eltrombopag 25 mg tablet
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eltrombopag 12.5 milligrams (mg) tabletDrug
eltrombopag 12.5 mg tablet once a day
eltrombopag 25 mg tabletDrug
eltrombopag 25 mg tablet once a day
| Study group | Role | What they receive |
|---|---|---|
| low dose | Experimental | eltrombopag 12.5 mg/day Receives: Drug: eltrombopag 12.5 milligrams (mg) tablet |
| middle dose | Experimental | eltrombopag 25 mg/day Receives: Drug: eltrombopag 25 mg tablet |
| high dose | Experimental | eltrombopag 37.5 mg/day Receives: Drug: eltrombopag 12.5 milligrams (mg) tablet; Drug: eltrombopag 25 mg tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Platelet Counts on Day 15
Platelet counts were measured by blood draw. Change from Baseline was calculated as the Day 15 value minus the Baseline value.
Measured: Baseline, Day 15
Secondary outcomes (16)
Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline Platelet Counts as Covariate)
Exploratory analysis was conducted to see a dose response/trend when a dose goes high with the changes from baseline in platelet counts (12.5 mg, 25 mg, and 37.5 mg) on Day 15 of each subject. The data were analyzed with baseline of platelet counts as covariate for the following dose response pattern using contrast: (1) linearity, (2) saturation at the medium dose, (3) onset of response at the high dose.
Measured: 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)
Exploratory analysis was conducted to see a dose response/trend when a dose goes high with the changes from baseline in platelet counts (12.5 mg, 25 mg, and 37.5 mg) on Day 15 of each subject. The data were analyzed with baseline of platelet counts and Child-Pugh class as covariate for the following dose response pattern using contrast: (1) linearity, (2) saturation at the medium dose, (3) onset of response at the high dose.
Measured: Baseline, Day 15
Percent Change From Baseline in Platelet Counts on Day 15
Platelet counts were measured by blood draw. Change from Baseline was calculated as the Day 15 value minus the Baseline value.
Measured: Baseline, Day 15
Platelet Counts by Treatment Visit
Platelet counts were measured by blood draw. The Final Assessment Point is the last visit during the treatment period, which is Day 15 or Day 22.
Measured: Day 1 (Baseline), Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
Platelet Counts by Post-Treatment Visit
Platelet counts were measured by blood draw.
Measured: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
Platelet Counts at Day 22
Platelet counts were measured by blood draw. The Final Assessment Point is the last visit during the treatment period, which is Day 15 or Day 22.
Measured: Day 22
Change From Baseline in Platelet Counts by Treatment Visit
Platelet counts were measured by blood draw. The Final Assessment Point is the last visit during the treatment period, which is Day 15 or Day 22. Change from Baseline was calculated as the value at each visit minus the Baseline value.
Measured: Baseline, Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
Change From Baseline in Platelet Counts by Post-Treatment Visit
Platelet counts were measured by blood draw. Change from Baseline was calculated as the value at each visit minus the Baseline value.
Measured: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
Percentage of Responders on Day 15
A responder was defined as a participant with a platelet count within the target range (>=80 x 10^9/Liter) on Day 15.
Measured: Day 15
Percentage of Responders on Day 22
A responder was defined as a participant with a platelet count within the target range (>=80 x 10^9/Liter) on Day 22 after receiving eltrombopag for an additional week from Day 15, on which his or her platelet count was <80 x 10^9/Liter.
Measured: Day 22
Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class
Change from Baseline was calculated as the Day 15 value minus the Baseline value. The Child-Pugh (CP) score (ranging from 5 to 15, with 5 being mild and 15 being severe), calculated based on total bilirubin, serum albumin, international normalized ratio, ascites, and hepatic encephalopathy, is used to assess the severity of liver disease. A CP score of 5 or 6 is classified as Class A (mild), a score of 7-9 is classified as Class B (moderate), and a score >=10 is classified as Class C (severe). Participants with a CP score <10 were enrolled in the study.
Measured: Baseline, Day 15
Change From Baseline in Platelet Counts on Day 15 by Sex
Change from Baseline was calculated as the Day 15 value minus the Baseline value. The numbers of females and males in each treatment group are illustrated by the "n's" in the category titles.
Measured: Baseline, Day 15
Change From Baseline in Platelet Counts on Day 15 by Age
Change from Baseline was calculated as the Day 15 value minus the Baseline value. The numbers of participants in each age category are illustrated by the "n's" in the category titles.
Measured: Baseline, Day 15
Log-transformed Cmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg
Serial PK samples were collected over a 24-hour (h) period on Days 14 and 15 in participants receiving eltrombopag 12.5 mg. A total of 8 blood samples (3 milliliters per sample) were collected at pre-dose, and at 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, and 24 h post-dose. Cmax=maximum drug concentration.
Measured: Day 14, Day 15
Log-transformed Tmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg
Serial PK samples were collected over a 24-hour (h) period on Days 14 and 15 in participants receiving eltrombopag 12.5 mg. A total of 8 blood samples (3 milliliters per sample) were collected at pre-dose, and at 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, and 24 h post-dose. Tmax=maximum drug concentration time.
Measured: 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
Serial PK samples were collected over a 24-hour (h) period on Days 14 and 15 in participants receiving eltrombopag 12.5 mg. A total of 8 blood samples (3 milliliters per sample) were collected at pre-dose, and at 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, and 24 h post-dose. AUC(0-t)=area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration, and AUC(0-24)=area under the concentration-time curve from 0 (pre-dose) to 24 hours.
Measured: Day 14, Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2009 (estimated)
- Study startJan 2009
- Primary completionAug 2009
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver DiseasesStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00861601
- Sponsor's protocol ID
- 111913
- Status last verified
- Feb 2011
- First submitted
- 5 Mar 2009
- Last updated
- 12 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
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 Dec;47(12):1342-51. doi: 10.1007/s00535-012-0600-5. Epub 2012 Jun 8.
PubMed 22674141
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00861601
- Acronym / sponsor ID
- 111913
- Conditions
- Liver Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jan 2009
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 13 Mar 2009 (estimated)
- Results
- Posted 23 Sep 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| low dose | Experimental | Drug: eltrombopag 12.5 milligrams (mg) tableteltrombopag 12.5 mg/day |
| middle dose | Experimental | Drug: eltrombopag 25 mg tableteltrombopag 25 mg/day |
| high dose | Experimental | Drug: eltrombopag 12.5 milligrams (mg) tablet, Drug: eltrombopag 25 mg tableteltrombopag 37.5 mg/day |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (22 listed)
- 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),
- hereditary thrombophilic disorders (e.g. antithrombinIII (ATIII) deficiency, etc.)
- hormone replacement therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| eltrombopag 12.5 milligrams (mg) tableteltrombopag 12.5 mg tablet once a day | Drug | high dose, low dose |
| eltrombopag 25 mg tableteltrombopag 25 mg tablet once a day | Drug | high dose, middle dose |
Primary outcome
Change From Baseline in Platelet Counts on Day 15
Time frame: Baseline, Day 15
Platelet counts were measured by blood draw. Change from Baseline was calculated as the Day 15 value minus the Baseline value.
16 secondary outcomes
Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline Platelet Counts as Covariate)
Time frame: 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)
Time frame: Baseline, Day 15
Percent Change From Baseline in Platelet Counts on Day 15
Time frame: Baseline, Day 15
Platelet Counts by Treatment Visit
Time frame: Day 1 (Baseline), Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
Platelet Counts by Post-Treatment Visit
Time frame: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
Platelet Counts at Day 22
Time frame: Day 22
Change From Baseline in Platelet Counts by Treatment Visit
Time frame: Baseline, Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
Change From Baseline in Platelet Counts by Post-Treatment Visit
Time frame: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
Percentage of Responders on Day 15
Time frame: Day 15
Percentage of Responders on Day 22
Time frame: Day 22
Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class
Time frame: Baseline, Day 15
Change From Baseline in Platelet Counts on Day 15 by Sex
Time frame: Baseline, Day 15
Change From Baseline in Platelet Counts on Day 15 by Age
Time frame: Baseline, Day 15
Log-transformed Cmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg
Time frame: Day 14, Day 15
Log-transformed Tmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg
Time frame: 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
Time frame: Day 14, Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22674141Kawaguchi 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.
Related trials for Liver Diseases
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Not yet recruitingObservational study
Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant
Hematopoietic Stem Cell Transplant
Not yet recruitingObservational study
Periodontal Status and Biomarkers in MASLD
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
RecruitingObservational study
Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis
Hepatitis D
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing eltrombopag 12.5 milligrams (mg) tablet and eltrombopag 25 mg tablet in people with Liver Diseases, run by GlaxoSmithKline at 10 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Platelet Counts on Day 15 (time frame: Baseline, Day 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00861601, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2015.