Liver Diseases
Conditions
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.
Interventions
DRUGeltrombopag 12.5 milligrams (mg) tablet
eltrombopag 12.5 mg tablet once a day
DRUGeltrombopag 25 mg tablet
eltrombopag 25 mg tablet once a day
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Platelet Counts on Day 15 | Baseline, Day 15 | Platelet counts were measured by blood draw. Change from Baseline was calculated as the Day 15 value minus the Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Baseline, Day 15 | 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. |
| Percent Change From Baseline in Platelet Counts on Day 15 | Baseline, Day 15 | Platelet counts were measured by blood draw. Change from Baseline was calculated as the Day 15 value minus the Baseline value. |
| Platelet Counts by Treatment Visit | Day 1 (Baseline), Day 8, Day 15, and Final Assessment Point (Day 15 or 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. |
| Platelet Counts by Post-Treatment Visit | 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment | Platelet counts were measured by blood draw. |
| Platelet Counts at Day 22 | 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. |
| Change From Baseline in Platelet Counts by Treatment Visit | Baseline, Day 8, Day 15, and Final Assessment Point (Day 15 or 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. Change from Baseline was calculated as the value at each visit minus the Baseline value. |
| Change From Baseline in Platelet Counts by Post-Treatment Visit | 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment | Platelet counts were measured by blood draw. Change from Baseline was calculated as the value at each visit minus the Baseline value. |
| Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline Platelet Counts as Covariate) | Baseline, Day 15 | 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. |
| Percentage of Responders on Day 22 | 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. |
| Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class | Baseline, Day 15 | 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. |
| Change From Baseline in Platelet Counts on Day 15 by Sex | Baseline, Day 15 | 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. |
| Change From Baseline in Platelet Counts on Day 15 by Age | Baseline, Day 15 | 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. |
| Log-transformed Cmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg | Day 14, Day 15 | 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. |
| Log-transformed Tmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg | Day 14, Day 15 | 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. |
| Log-transformed AUC(0-t) and AUC(0-24) on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg | Day 14, Day 15 | 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. |
| Percentage of Responders on Day 15 | 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eltrombopag 12.5 mg Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days. | 12 |
| Eltrombopag 25 mg Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count \<80 x 10\^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate. | 14 |
| Eltrombopag 37.5 mg Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count \<80 x 10\^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate. | 12 |
| Total | 38 |
Baseline characteristics
| Characteristic | Eltrombopag 12.5 mg | Eltrombopag 25 mg | Eltrombopag 37.5 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 10.51 | 57.7 years STANDARD_DEVIATION 8.69 | 66.3 years STANDARD_DEVIATION 8.84 | 61.8 years STANDARD_DEVIATION 9.78 |
| Number of participants categorized into the indicated Child-Pugh (CP) Class Class A | 8 participants | 8 participants | 7 participants | 23 participants |
| Number of participants categorized into the indicated Child-Pugh (CP) Class Class B | 4 participants | 6 participants | 5 participants | 15 participants |
| Number of participants categorized into the indicated Child-Pugh (CP) Class Class C | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian-Japanese Heritage | 12 participants | 14 participants | 12 participants | 38 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 8 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 12 | 7 / 14 | 9 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 14 | 1 / 12 |
Outcome results
Primary
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.
Time frame: Baseline, Day 15
Population: Full Analysis Set (FAS): all enrolled participants, excluding those who received no doses of eltrombopag during the treatment period, those without a baseline platelet assessment, and those without at least one on-therapy (scheduled or unscheduled) platelet assessment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts on Day 15 | 24.8 10^9/Liter |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts on Day 15 | 54.0 10^9/Liter |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts on Day 15 | 60.0 10^9/Liter |
Secondary
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.
Time frame: Baseline, Day 15
Population: FAS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eltrombopag 12.5 mg | 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) | 24.8 10^9/Liter |
| Eltrombopag 25 mg | 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) | 54.0 10^9/Liter |
| Eltrombopag 37.5 mg | 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) | 60.0 10^9/Liter |
p-value: 0.0116ANCOVA
p-value: 0.0066ANCOVA
p-value: 0.0846ANCOVA
Secondary
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.
Time frame: Baseline, Day 15
Population: FAS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eltrombopag 12.5 mg | Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline Platelet Counts as Covariate) | 24.8 10^9/Liter |
| Eltrombopag 25 mg | Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline Platelet Counts as Covariate) | 54.0 10^9/Liter |
| Eltrombopag 37.5 mg | Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline Platelet Counts as Covariate) | 60.0 10^9/Liter |
p-value: 0.0104ANCOVA
p-value: 0.0057ANCOVA
p-value: 0.0808ANCOVA
Secondary
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.
Time frame: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
Population: FAS. The number of participants analyzed varies by visit, because the platelet count data on 4 days post-treatment in one participant in the 37.5 mg group is missing and the platelet count data post-specific therapies affecting the evaluation of efficacy are excluded from this efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts by Post-Treatment Visit | 15 days post-treatment, n=11, 13, 11 | 35.7 10^9/Liter | Standard Deviation 36.58 |
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts by Post-Treatment Visit | 8 days post-treatment, n=12, 13, 12 | 41.5 10^9/Liter | Standard Deviation 40.5 |
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts by Post-Treatment Visit | 4 days post-treatment, n=12, 13, 11 | 33.0 10^9/Liter | Standard Deviation 36.36 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts by Post-Treatment Visit | 15 days post-treatment, n=11, 13, 11 | 82.2 10^9/Liter | Standard Deviation 83.13 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts by Post-Treatment Visit | 4 days post-treatment, n=12, 13, 11 | 73.8 10^9/Liter | Standard Deviation 50.14 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts by Post-Treatment Visit | 8 days post-treatment, n=12, 13, 12 | 100.9 10^9/Liter | Standard Deviation 81.96 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts by Post-Treatment Visit | 8 days post-treatment, n=12, 13, 12 | 108.3 10^9/Liter | Standard Deviation 81.26 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts by Post-Treatment Visit | 4 days post-treatment, n=12, 13, 11 | 97.6 10^9/Liter | Standard Deviation 83.38 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts by Post-Treatment Visit | 15 days post-treatment, n=11, 13, 11 | 83.0 10^9/Liter | Standard Deviation 68.31 |
Secondary
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.
Time frame: Baseline, Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
Population: FAS. The number of participants analyzed varies by visit, because the platelet count data on 4 days post-treatment in one participant in the 37.5 mg group is missing and the platelet count data post-specific therapies affecting the evaluation of efficacy are excluded from this efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts by Treatment Visit | Day 15 | 24.8 10^9/Liter | Standard Deviation 26.13 |
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts by Treatment Visit | Final Assessment Point | 24.8 10^9/Liter | Standard Deviation 26.13 |
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts by Treatment Visit | Day 8 | 6.9 10^9/Liter | Standard Deviation 9.43 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts by Treatment Visit | Day 15 | 54.0 10^9/Liter | Standard Deviation 44.7 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts by Treatment Visit | Final Assessment Point | 64.0 10^9/Liter | Standard Deviation 42.51 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts by Treatment Visit | Day 8 | 14.6 10^9/Liter | Standard Deviation 11.8 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts by Treatment Visit | Final Assessment Point | 61.9 10^9/Liter | Standard Deviation 47.77 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts by Treatment Visit | Day 15 | 60.0 10^9/Liter | Standard Deviation 48.36 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts by Treatment Visit | Day 8 | 15.4 10^9/Liter | Standard Deviation 8.96 |
Secondary
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.
Time frame: Baseline, Day 15
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts on Day 15 by Age | >=65 years of age, n=5, 3, 7 | 32.0 10^9/Liter | Standard Deviation 30.82 |
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts on Day 15 by Age | <65 years of age, n=7, 11, 5 | 19.7 10^9/Liter | Standard Deviation 23.34 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts on Day 15 by Age | <65 years of age, n=7, 11, 5 | 40.2 10^9/Liter | Standard Deviation 24.5 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts on Day 15 by Age | >=65 years of age, n=5, 3, 7 | 104.7 10^9/Liter | Standard Deviation 71.32 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts on Day 15 by Age | <65 years of age, n=7, 11, 5 | 49.8 10^9/Liter | Standard Deviation 30.36 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts on Day 15 by Age | >=65 years of age, n=5, 3, 7 | 67.3 10^9/Liter | Standard Deviation 59.36 |
Secondary
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.
Time frame: Baseline, Day 15
Population: FAS. The number of participants categorized as Class A or Class B is given in the category titles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class | Child-Pugh Class A, n=8, 8, 7 | 24.4 10^9/Liter | Standard Deviation 32.51 |
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class | Child-Pugh Class B, n=4, 6, 5 | 25.8 10^9/Liter | Standard Deviation 5.97 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class | Child-Pugh Class A, n=8, 8, 7 | 44.5 10^9/Liter | Standard Deviation 27.02 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class | Child-Pugh Class B, n=4, 6, 5 | 66.7 10^9/Liter | Standard Deviation 61.93 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class | Child-Pugh Class A, n=8, 8, 7 | 66.6 10^9/Liter | Standard Deviation 60.59 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class | Child-Pugh Class B, n=4, 6, 5 | 50.8 10^9/Liter | Standard Deviation 27.23 |
Secondary
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.
Time frame: Baseline, Day 15
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts on Day 15 by Sex | Female, n=4, 4, 4 | 47.3 10^9/Liter | Standard Deviation 31.16 |
| Eltrombopag 12.5 mg | Change From Baseline in Platelet Counts on Day 15 by Sex | Male, n=8, 10, 8 | 13.6 10^9/Liter | Standard Deviation 15.03 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts on Day 15 by Sex | Male, n=8, 10, 8 | 42.2 10^9/Liter | Standard Deviation 26.96 |
| Eltrombopag 25 mg | Change From Baseline in Platelet Counts on Day 15 by Sex | Female, n=4, 4, 4 | 83.5 10^9/Liter | Standard Deviation 69.67 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts on Day 15 by Sex | Male, n=8, 10, 8 | 40.6 10^9/Liter | Standard Deviation 23.81 |
| Eltrombopag 37.5 mg | Change From Baseline in Platelet Counts on Day 15 by Sex | Female, n=4, 4, 4 | 98.8 10^9/Liter | Standard Deviation 65.18 |
Secondary
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.
Time frame: Day 14, Day 15
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Eltrombopag 12.5 mg | Log-transformed AUC(0-t) and AUC(0-24) on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg | AUC(0-t) | 65244.180 hours * ng/ml |
| Eltrombopag 12.5 mg | Log-transformed AUC(0-t) and AUC(0-24) on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg | AUC(0-24) | 65235.699 hours * ng/ml |
Secondary
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.
Time frame: Day 14, Day 15
Population: PK Parameter Population: all participants from whom a PK sample was obtained and analyzed and whose PK parameter data was evaluated. One of the 12 participants took a prohibited medication that might have decreased the absorption of eltrombopag during the treatment period and was hence excluded from the PK Parameter Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Eltrombopag 12.5 mg | Log-transformed Cmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg | 3412.999 nanograms/milliliter (ng/ml) |
Secondary
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.
Time frame: Day 14, Day 15
Population: PK Parameter Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Eltrombopag 12.5 mg | Log-transformed Tmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg | 3.444 hours |
Secondary
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.
Time frame: Day 15
Population: FAS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eltrombopag 12.5 mg | Percentage of Responders on Day 15 | 25.0 percentage of responders |
| Eltrombopag 25 mg | Percentage of Responders on Day 15 | 42.9 percentage of responders |
| Eltrombopag 37.5 mg | Percentage of Responders on Day 15 | 58.3 percentage of responders |
Secondary
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.
Time frame: Day 22
Population: FAS. Participants in the 12.5 mg group have no data on Day 22 because they received the medication for only 14 days. Only 6 participants in the 25 mg group and 2 participants in the 37.5 mg group received the medication for an additional week, because they had a platelet count \<80 x 10\^9/Liter on Day 15.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eltrombopag 25 mg | Percentage of Responders on Day 22 | 50.0 percentage of responders |
| Eltrombopag 37.5 mg | Percentage of Responders on Day 22 | 50.0 percentage of responders |
Secondary
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.
Time frame: Baseline, Day 15
Population: FAS
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eltrombopag 12.5 mg | Percent Change From Baseline in Platelet Counts on Day 15 | 57.86 Percent change |
| Eltrombopag 25 mg | Percent Change From Baseline in Platelet Counts on Day 15 | 134.57 Percent change |
| Eltrombopag 37.5 mg | Percent Change From Baseline in Platelet Counts on Day 15 | 158.45 Percent change |
Secondary
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.
Time frame: Day 22
Population: FAS. Participants in the 12.5 mg group have no data on Day 22 because they received the medication for only 14 days. Only 6 participants in the 25 mg group and 2 participants in the 37.5 mg group received the medication for an additional week, because they had a platelet count \<80 x 10\^9/Liter on Day 15.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eltrombopag 25 mg | Platelet Counts at Day 22 | 82.5 10^9/Liter |
| Eltrombopag 37.5 mg | Platelet Counts at Day 22 | 72.5 10^9/Liter |
Secondary
Platelet Counts by Post-Treatment Visit
Platelet counts were measured by blood draw.
Time frame: 4 days post-treatment, 8 days post-treatment, and 15 days post-treatment
Population: FAS. The number of participants analyzed varies by visit, because the platelet count data on 4 days post-treatment in one participant in the 37.5 mg group are missing and the platelet count data post-specific therapies affecting the evaluation of efficacy are excluded from this efficacy analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Eltrombopag 12.5 mg | Platelet Counts by Post-Treatment Visit | 8 days post-treatment, n=12, 13, 12 | 67.5 10^9/Liter |
| Eltrombopag 12.5 mg | Platelet Counts by Post-Treatment Visit | 4 days post-treatment, n=12, 13, 11 | 63.5 10^9/Liter |
| Eltrombopag 12.5 mg | Platelet Counts by Post-Treatment Visit | 15 days post-treatment, n=11, 13, 11 | 65.0 10^9/Liter |
| Eltrombopag 25 mg | Platelet Counts by Post-Treatment Visit | 8 days post-treatment, n=12, 13, 12 | 119.0 10^9/Liter |
| Eltrombopag 25 mg | Platelet Counts by Post-Treatment Visit | 4 days post-treatment, n=12, 13, 11 | 100.0 10^9/Liter |
| Eltrombopag 25 mg | Platelet Counts by Post-Treatment Visit | 15 days post-treatment, n=11, 13, 11 | 87.0 10^9/Liter |
| Eltrombopag 37.5 mg | Platelet Counts by Post-Treatment Visit | 4 days post-treatment, n=12, 13, 11 | 109.0 10^9/Liter |
| Eltrombopag 37.5 mg | Platelet Counts by Post-Treatment Visit | 15 days post-treatment, n=11, 13, 11 | 97.0 10^9/Liter |
| Eltrombopag 37.5 mg | Platelet Counts by Post-Treatment Visit | 8 days post-treatment, n=12, 13, 12 | 120.0 10^9/Liter |
Secondary
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.
Time frame: Day 1 (Baseline), Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)
Population: FAS. The number of participants analyzed varies by visit, because the platelet count data on 4 days post-treatment in one participant in the 37.5 mg group are missing and the platelet count data post-specific therapies affecting the evaluation of efficacy are excluded from this efficacy analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Eltrombopag 12.5 mg | Platelet Counts by Treatment Visit | Day 1 | 42.5 10^9/Liter |
| Eltrombopag 12.5 mg | Platelet Counts by Treatment Visit | Final Assessment Point | 66.0 10^9/Liter |
| Eltrombopag 12.5 mg | Platelet Counts by Treatment Visit | Day 8 | 50.5 10^9/Liter |
| Eltrombopag 12.5 mg | Platelet Counts by Treatment Visit | Day 15 | 66.0 10^9/Liter |
| Eltrombopag 25 mg | Platelet Counts by Treatment Visit | Final Assessment Point | 95.5 10^9/Liter |
| Eltrombopag 25 mg | Platelet Counts by Treatment Visit | Day 1 | 38.0 10^9/Liter |
| Eltrombopag 25 mg | Platelet Counts by Treatment Visit | Day 8 | 49.5 10^9/Liter |
| Eltrombopag 25 mg | Platelet Counts by Treatment Visit | Day 15 | 73.0 10^9/Liter |
| Eltrombopag 37.5 mg | Platelet Counts by Treatment Visit | Day 8 | 52.0 10^9/Liter |
| Eltrombopag 37.5 mg | Platelet Counts by Treatment Visit | Final Assessment Point | 85.5 10^9/Liter |
| Eltrombopag 37.5 mg | Platelet Counts by Treatment Visit | Day 15 | 81.5 10^9/Liter |
| Eltrombopag 37.5 mg | Platelet Counts by Treatment Visit | Day 1 | 40.0 10^9/Liter |