Chronic Liver Disease, HBV, HCV, Hepatitis B Virus, Hepatitis C Virus, HIV Infection, Human Immunodeficiency Virus, Liver Diseases, NASH - Nonalcoholic Steatohepatitis, Non-alcoholic Steatohepatitis, Thrombocytopenia
Conditions
Keywords
elective invasive procedure., platelet transfusion, chronic liver disease-related thrombocytopenia, platelets, thrombopoietin
Brief summary
The purpose of this study is to assess the ability of eltrombopag to elevate platelet counts thereby reducing the need for platelet transfusions in chronic liver disease patients with thrombocytopenia undergoing elective invasive procedures. The clinical benefit of eltrombopag will be measured by the proportion of subjects who avoid platelet transfusions, before, during and up to 7 days after undergoing an invasive procedure. In addition, bleeding events will be monitored during this time. The number of transfusions, safety events and medical resource utilisation will be monitored during this time and for up to 30 days after undergoing an invasive procedure to help further evaluate clinical benefit.
Interventions
DRUGEltrombopag
75 mg, once daily, oral
DRUGPlacebo
placebo, once daily, oral
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects, 18 years of age or more with chronic liver disease. * Child-Pugh score of 12 or less. * Model of End Stage Liver Disease (MELD) score of 24 or less. * Subjects who, in the opinion of the investigator, are appropriate candidates to undergo an elective invasive procedure and who require a platelet transfusion to manage the risk of bleeding associated with the procedure. * A baseline platelet count \<50,000/µL. * A baseline serum sodium level \>130mEq/L. * Haemoglobin concentration \>8g/dL stable for at least one month. * 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 greater 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 for two weeks before exposure to the study drug, throughout the clinical study, and for 28 days after completion or premature discontinuation from the study to account for the elimination of the study drug (minimum of 5 half-lives). * 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 (either combined or progesterone only). * Any other contraceptive method with a documented failure rate of \<1% per year. * Subject has no physical limitation to ingest and retain oral medication. * Subject is able to understand and comply with protocol requirements and instructions and is likely to complete the study as planned. * Subject is able to provide signed and dated written informed consent. * In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion criteria
* Subjects with a known 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 MRI/CT imaging techniques) within 3 months of study start. * History of arterial or venous thrombosis, including Budd-Chiari Syndrome, AND ≥ two of the following risk factors: hereditary thrombophilic disorders (e.g. Factor V Leiden, ATIII deficiency, etc.), hormone replacement therapy, systemic contraception therapy (containing oestrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer. * Any disease condition associated with current active WHO Grade 3 or 4 bleeding. * Active infection requiring systemic antibiotic therapy. Prophylactic use of antibiotics is permitted. * Pregnant or nursing women. * 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 that prevents reliable measurement of platelet counts. * History of porphyria. * Previous participation in TPL104054.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Chronic Liver Disease and Thrombocytopenia (Platelets <50 Gi/L) Who do Not Require a Platelet Transfusion Prior to, During, and up to 7 Days Following Elective Invasive Procedures | Prior to, during, and up to seven days following elective invasive procedures (Study Days 16-19); therefore, this covers a time period from Baseline to Day 26 | A platelet transfusion was given if the platelet count was \<50 giga (10\^9) per liter (Gi/L) before the procedure. A platelet transfusion was not given if the platelet count was \>80 Gi/L (based on a primary endpoint of success). For participants with platelet counts between 50 Gi/L and 80 Gi/L, platelet transfusions were administered at the discretion of the investigator and the physician performing the elective invasive procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Indicated Number of Platelet Transfusions Administered | Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26 | Platelet transfusion use was documented at every visit throughout the study from screening until the 4-week (30-day) post-procedure follow-up visit or at the time of participant withdrawal from the study. |
| Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 day follow-up; early withdrawal; and maximum post-baseline | Procedure +7 = Days 23-26; +14 = Days 30-33; +21 = Days 37-40; +30 = Days 46-49. Early withdrawal can occur at any time. Maximum post-baseline refers to any time point listed above for which the maximum value was reached (therefore this time point is variable). |
| Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 day follow-up; and maximum post-baseline | Procedure +7 = Days 23-26; +14 = Days 30-33; +21 = Days 37-40; +30 = Days 46-49. Early withdrawal can occur at any time. Maximum post-baseline refers to any time point listed above for which the maximum value was reached (therefore this time point is variable). |
| Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Screening to Procedure +30 day follow-up or early withdrawal | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect or an ocular event of clinical concern. Medical or scientific judgement is exercised in deciding whether reporting is appropriate in other situations. |
| Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant | Screening to Procedure +30 day follow-up or early withdrawal | — |
| Number of Participants With the Indicated Event Relating to Vision | Screening or Baseline and at End of Study (Procedure +30 day follow-up or withdrawal visit) | The progression of pre-existing cataracts was measured by the use of slit lamp examination. Decrease in visual acuity is defined as the loss of 3 or more lines of visual acuity in either eye (0.3 log minimal angle of resolution \[logMAR\], 15 letters on the standard Early Treatment Diabetic Retinopathy Study chart). |
| Number of Participants With Renal Function Abnormality | Screening to Procedure +30 day follow-up or early withdrawal | Renal function abnormality was defined by threshold values for: serum creatinine: change from baseline of \>=0.3 and \<0.5 milligrams (mg)/deciliter (dL) (\>=26.6 and \<44.3 micromoles \[umol\]/L) or change from baseline of \>=0.5 mg/dL (\>=44.3 umol/L); microscopic urine analysis: cellular casts pathologic (as defined by local standards of microscopic urine analysis); urine protein/creatinine ratio (UP/CR): \>0.5 mg/mg; Glomerular Filtration Rate (GFR) as determined by the Cockcroft-Gault formula and urine dipstick test. |
| Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures | Prior to, during, and up to 7 days following elective invasive procedures (Study Days 16-19); therefore, this covers a time period from Baseline to Day 26 | The WHO Bleeding Scale was used to assess bleeding during the study. The range of possible scores is 0 to 4. Grade 0 is no bleeding; Grade 1 is petechiae (small \[1-2 millimeter\] red or purple spot on the body, caused by a minor hemorrhage); Grade 2 is mild blood loss; Grade 3 is gross blood loss (requiring a transfusion; and Grade 4 is debilitating blood loss (retinal or cerebral associated with fatality). |
| Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau) | Day 14 | AUC(0-tau) is the area under a concentration versus time curve between dose interval following repeat dosing. It is a measure of systemic drug exposure. |
| Pharmacokinetics (PK) of Eltrombopag, Cmax | Day 14 | Cmax is the steady state peak plasma concentration of a drug observed after its administration. |
| Pharmacokinetics (PK) of Eltrombopag, t1/2 | Day 14 | t1/2 is the half life of a drug based on its terminal phase. Half life is defined as the time necessary to halve the plasma concentration. |
| Pharmacokinetics (PK) of Eltrombopag, CL/F | Day 14 | CL/F is the apparent plasma clearance, where CL is an estimate of the total body clearance, and F is the fraction of dose absorbed. Total clearance is the volume of blood cleared of the drug by the various elimination processes (metabolism and excretion) per unit time. |
| Mean Number of Days Spent in the Hospital | Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26 | The number of days spent in the hospital was analyzed as an indication of medical resource utilization throughout the study. |
| Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures | Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26 | The number of unscheduled events was analyzed as an indication of medical resource utilization throughout the study. |
| Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results | Screening, Baseline, Day 15, and Withdrawal | A 12-lead ECG was obtained in duplicate at screening, baseline, Day 15, and withdrawal from the study. Participants rested supine for 5 minutes before the 12-lead ECG was recorded. A 30 second rhythm strip was obtained, and the ECG was calibrated, labelled, and initialled by the person performing the recording. A written, interpretive assessment detailing clinical significance was produced, dated, and signed off by the physician at the site. |
Countries
Argentina, Belgium, Canada, France, India, Italy, Pakistan, Poland, Russia, South Korea, Spain, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo | 147 |
| Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily | 145 |
| Total | 292 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Investigator Discretion | 2 | 6 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Study Closed/Terminated | 1 | 0 |
| Overall Study | Withdrew Consent | 8 | 3 |
Baseline characteristics
| Characteristic | Placebo | Eltrombopag 75 mg | Total |
|---|---|---|---|
| Age, Continuous | 53.5 Years STANDARD_DEVIATION 11.78 | 51.6 Years STANDARD_DEVIATION 11.04 | 52.5 Years STANDARD_DEVIATION 11.44 |
| Model for End-Stage Liver Disease (MELD) Score at Baseline | 12 scores on a scale | 12 scores on a scale | 12 scores on a scale |
| Number of participants categorized into the indicated Child-Pugh (CP) Class Child-Pugh Class A | 59 participants | 68 participants | 127 participants |
| Number of participants categorized into the indicated Child-Pugh (CP) Class Child-Pugh Class B | 64 participants | 57 participants | 121 participants |
| Number of participants categorized into the indicated Child-Pugh (CP) Class Child-Pugh Class C | 17 participants | 10 participants | 27 participants |
| Race/Ethnicity, Customized African American/African Heritage | 2 participants | 4 participants | 6 participants |
| Race/Ethnicity, Customized Central/South Asian Heritage | 33 participants | 41 participants | 74 participants |
| Race/Ethnicity, Customized Japanese/East Asian/South East Asian Heritage | 19 participants | 14 participants | 33 participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander and White | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 93 participants | 85 participants | 178 participants |
| Sex: Female, Male Female | 55 Participants | 49 Participants | 104 Participants |
| Sex: Female, Male Male | 92 Participants | 96 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 145 | 40 / 143 |
| serious Total, serious adverse events | 17 / 145 | 19 / 143 |
Outcome results
Primary
Number of Participants With Chronic Liver Disease and Thrombocytopenia (Platelets <50 Gi/L) Who do Not Require a Platelet Transfusion Prior to, During, and up to 7 Days Following Elective Invasive Procedures
A platelet transfusion was given if the platelet count was \<50 giga (10\^9) per liter (Gi/L) before the procedure. A platelet transfusion was not given if the platelet count was \>80 Gi/L (based on a primary endpoint of success). For participants with platelet counts between 50 Gi/L and 80 Gi/L, platelet transfusions were administered at the discretion of the investigator and the physician performing the elective invasive procedure.
Time frame: Prior to, during, and up to seven days following elective invasive procedures (Study Days 16-19); therefore, this covers a time period from Baseline to Day 26
Population: Intent-to-Treat (ITT) Population: all participants who were randomized to treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Chronic Liver Disease and Thrombocytopenia (Platelets <50 Gi/L) Who do Not Require a Platelet Transfusion Prior to, During, and up to 7 Days Following Elective Invasive Procedures | 28 participants |
| Eltrombopag 75 mg | Number of Participants With Chronic Liver Disease and Thrombocytopenia (Platelets <50 Gi/L) Who do Not Require a Platelet Transfusion Prior to, During, and up to 7 Days Following Elective Invasive Procedures | 104 participants |
p-value: <0.000195% CI: [43.2, 62.4]Cochran-Mantel-Haenszel
Secondary
Mean Number of Days Spent in the Hospital
The number of days spent in the hospital was analyzed as an indication of medical resource utilization throughout the study.
Time frame: Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26
Population: ITT Population. Data are missing for some participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Number of Days Spent in the Hospital | 1.3 days | Standard Deviation 3.77 |
| Eltrombopag 75 mg | Mean Number of Days Spent in the Hospital | 1.7 days | Standard Deviation 6.43 |
Secondary
Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures
The number of unscheduled events was analyzed as an indication of medical resource utilization throughout the study.
Time frame: Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26
Population: ITT Population. Data are missing for some participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures | Unscheduled laboratory tests | 1.1 unscheduled events | Standard Deviation 3.78 |
| Placebo | Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures | Unscheduled procedures | 0.3 unscheduled events | Standard Deviation 0.81 |
| Placebo | Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures | Unscheduled office visits | 0.8 unscheduled events | Standard Deviation 1.64 |
| Eltrombopag 75 mg | Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures | Unscheduled laboratory tests | 1.8 unscheduled events | Standard Deviation 5.67 |
| Eltrombopag 75 mg | Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures | Unscheduled office visits | 1.0 unscheduled events | Standard Deviation 2.91 |
| Eltrombopag 75 mg | Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures | Unscheduled procedures | 0.4 unscheduled events | Standard Deviation 1.65 |
Secondary
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline
Procedure +7 = Days 23-26; +14 = Days 30-33; +21 = Days 37-40; +30 = Days 46-49. Early withdrawal can occur at any time. Maximum post-baseline refers to any time point listed above for which the maximum value was reached (therefore this time point is variable).
Time frame: Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 day follow-up; early withdrawal; and maximum post-baseline
Population: ITT Population. The number of participants analyzed decreases over time due to missing measurements and to participants dropping out of the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Screening, n=147, 145 | 40.0 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Procedure + 7 day follow-up, n=128, 125 | 44.0 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Day 8, n=139, 134 | 41.0 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Procedure + 14 day follow-up, n=116, 125 | 47.5 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Early withdrawal, n=9, 8 | 40.0 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Day 15, n=132, 131 | 39.0 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Procedure + 30 day follow-up, n=125, 127 | 40.0 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Day 1, n=145, 141 | 40.0 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Days 16-19, n=50, 49 | 41.5 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Maximum post-baseline, n=144, 140 | 53.0 Gi/L |
| Placebo | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Procedure + 21 day follow-up, n=120, 117 | 44.5 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Maximum post-baseline, n=144, 140 | 152 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Screening, n=147, 145 | 40.0 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Day 1, n=145, 141 | 40.0 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Day 8, n=139, 134 | 58.5 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Day 15, n=132, 131 | 103.0 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Days 16-19, n=50, 49 | 107.0 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Procedure + 7 day follow-up, n=128, 125 | 148 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Procedure + 14 day follow-up, n=116, 125 | 110 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Procedure + 21 day follow-up, n=120, 117 | 62.0 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Procedure + 30 day follow-up, n=125, 127 | 50.0 Gi/L |
| Eltrombopag 75 mg | Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline | Early withdrawal, n=9, 8 | 41.0 Gi/L |
Secondary
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect or an ocular event of clinical concern. Medical or scientific judgement is exercised in deciding whether reporting is appropriate in other situations.
Time frame: Screening to Procedure +30 day follow-up or early withdrawal
Population: Safety population: all randomized participants who received at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Incident cataract develpment n=145,143 | 2 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Death on study | 2 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Bleeding AEs | 25 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | SAEs in >1 participant during study | 17 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Drug-related AEs in >1 participant | 15 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Hepatobiliary AEs | 16 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Thrombocytopenia | 1 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | AEs during study | 85 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Progression of pre-existing cataract n=145,143 | 2 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Malignancy AEs | 1 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Throboembolic AEs | 2 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Decrease in visual acuity n=121,124 | 19 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Renal AEs | 4 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Renal function abnormality n=145,143 | 27 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Clinically significant change in ECG n=128,130 | 0 participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Drug-related SAEs in >1 participant | 4 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Clinically significant change in ECG n=128,130 | 1 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Renal function abnormality n=145,143 | 28 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | AEs during study | 79 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Drug-related AEs in >1 participant | 31 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Throboembolic AEs | 6 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Bleeding AEs | 19 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Hepatobiliary AEs | 24 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Malignancy AEs | 1 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Renal AEs | 2 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Death on study | 3 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | SAEs in >1 participant during study | 19 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Drug-related SAEs in >1 participant | 9 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Thrombocytopenia | 1 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Progression of pre-existing cataract n=145,143 | 0 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Incident cataract develpment n=145,143 | 4 participants |
| Eltrombopag 75 mg | Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category | Decrease in visual acuity n=121,124 | 21 participants |
Secondary
Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results
A 12-lead ECG was obtained in duplicate at screening, baseline, Day 15, and withdrawal from the study. Participants rested supine for 5 minutes before the 12-lead ECG was recorded. A 30 second rhythm strip was obtained, and the ECG was calibrated, labelled, and initialled by the person performing the recording. A written, interpretive assessment detailing clinical significance was produced, dated, and signed off by the physician at the site.
Time frame: Screening, Baseline, Day 15, and Withdrawal
Population: Safety Population. Data were missing for some participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results | 0 participants |
| Eltrombopag 75 mg | Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results | 1 participants |
Secondary
Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant
Time frame: Screening to Procedure +30 day follow-up or early withdrawal
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant | 4 participants |
| Eltrombopag 75 mg | Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant | 9 participants |
Secondary
Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures
The WHO Bleeding Scale was used to assess bleeding during the study. The range of possible scores is 0 to 4. Grade 0 is no bleeding; Grade 1 is petechiae (small \[1-2 millimeter\] red or purple spot on the body, caused by a minor hemorrhage); Grade 2 is mild blood loss; Grade 3 is gross blood loss (requiring a transfusion; and Grade 4 is debilitating blood loss (retinal or cerebral associated with fatality).
Time frame: Prior to, during, and up to 7 days following elective invasive procedures (Study Days 16-19); therefore, this covers a time period from Baseline to Day 26
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures | 34 participants |
| Eltrombopag 75 mg | Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures | 25 participants |
95% CI: [-15.1, 3.3]
Secondary
Number of Participants With Renal Function Abnormality
Renal function abnormality was defined by threshold values for: serum creatinine: change from baseline of \>=0.3 and \<0.5 milligrams (mg)/deciliter (dL) (\>=26.6 and \<44.3 micromoles \[umol\]/L) or change from baseline of \>=0.5 mg/dL (\>=44.3 umol/L); microscopic urine analysis: cellular casts pathologic (as defined by local standards of microscopic urine analysis); urine protein/creatinine ratio (UP/CR): \>0.5 mg/mg; Glomerular Filtration Rate (GFR) as determined by the Cockcroft-Gault formula and urine dipstick test.
Time frame: Screening to Procedure +30 day follow-up or early withdrawal
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Renal Function Abnormality | 27 participants |
| Eltrombopag 75 mg | Number of Participants With Renal Function Abnormality | 28 participants |
Secondary
Number of Participants With the Indicated Event Relating to Vision
The progression of pre-existing cataracts was measured by the use of slit lamp examination. Decrease in visual acuity is defined as the loss of 3 or more lines of visual acuity in either eye (0.3 log minimal angle of resolution \[logMAR\], 15 letters on the standard Early Treatment Diabetic Retinopathy Study chart).
Time frame: Screening or Baseline and at End of Study (Procedure +30 day follow-up or withdrawal visit)
Population: Safety Population: all randomized participants who received at least one dose of study medication. Data are missing for some participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Event Relating to Vision | Progression of pre-existing cataract, n=145, 143 | 2 participants |
| Placebo | Number of Participants With the Indicated Event Relating to Vision | Cataract development, n=145, 143 | 2 participants |
| Placebo | Number of Participants With the Indicated Event Relating to Vision | Decrease in visual acuity, n=121, 124 | 19 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Event Relating to Vision | Progression of pre-existing cataract, n=145, 143 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Event Relating to Vision | Cataract development, n=145, 143 | 4 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Event Relating to Vision | Decrease in visual acuity, n=121, 124 | 21 participants |
Secondary
Number of Participants With the Indicated Number of Platelet Transfusions Administered
Platelet transfusion use was documented at every visit throughout the study from screening until the 4-week (30-day) post-procedure follow-up visit or at the time of participant withdrawal from the study.
Time frame: Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 0 | 30 participants |
| Placebo | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 1 | 93 participants |
| Placebo | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 2 | 3 participants |
| Placebo | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 3 | 2 participants |
| Placebo | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 4 | 3 participants |
| Placebo | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 5 | 0 participants |
| Placebo | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 6 | 1 participants |
| Placebo | Number of Participants With the Indicated Number of Platelet Transfusions Administered | Died/withdrew prior to any platelet transfusions | 15 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Number of Platelet Transfusions Administered | Died/withdrew prior to any platelet transfusions | 14 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 0 | 106 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 4 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 1 | 24 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 6 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 2 | 1 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 5 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Number of Platelet Transfusions Administered | 3 | 0 participants |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline
Procedure +7 = Days 23-26; +14 = Days 30-33; +21 = Days 37-40; +30 = Days 46-49. Early withdrawal can occur at any time. Maximum post-baseline refers to any time point listed above for which the maximum value was reached (therefore this time point is variable).
Time frame: Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 day follow-up; and maximum post-baseline
Population: ITT Population. The number of participants analyzed decreases over time due to missing measurements and to participants dropping out of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, >400 Gi/L, n=139, 135 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, >200-<=400 Gi/L, n=128, 126 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, >400 Gi/L, n=147, 145 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, >400 Gi/L, n=128, 126 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, <50 Gi/L, n=132, 131 | 98 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, <50 Gi/L, n=117, 125 | 63 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, >80-<=200 Gi/L, n=147, 145 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, >=50-<=80 Gi/L, n=117, 125 | 40 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, >=50-<=80 Gi/L, n=132, 131 | 26 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, >80-<=200 Gi/L, n=117, 125 | 11 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, <50 Gi/L, n=139, 135 | 98 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, >200-<=400 Gi/L, n=117, 125 | 2 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, >80-<=200 Gi/L, n=132, 131 | 8 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, >400 Gi/L, n=117, 125 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, >=50-<=80 Gi/L, n=147, 145 | 14 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, <50 Gi/L, n=121, 117 | 80 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, >200-<=400 Gi/L, n=132, 131 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, >=50-<=80 Gi/L, n=121, 117 | 30 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, >=50-<=80 Gi/L, n=139, 135 | 34 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, >80-<=200 Gi/L, n=121, 117 | 10 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, >400 Gi/L, n=132, 131 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, >200-<=400 Gi/L, n=121, 117 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, >200-<=400 Gi/L, n=147, 145 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, >400 Gi/L, n=121, 117 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, <50 Gi/L, n=128, 126 | 78 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, <50 Gi/L, n=144, 140 | 60 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, >80-<=200 Gi/L, n=139, 135 | 7 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, >=50-<=80 Gi/L, n=144, 140 | 53 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, >=50-<=80 Gi/L, n=128, 126 | 38 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, >80-<=200 Gi/L, n=144, 140 | 28 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, <50 Gi/L, n=147, 145 | 133 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, >200-<=400 Gi/L, n=144, 140 | 3 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, >80-<=200 Gi/L, n=128, 126 | 12 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, >400 Gi/L, n=144, 140 | 0 participants |
| Placebo | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, >200-<=400 Gi/L, n=139, 135 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, >400 Gi/L, n=144, 140 | 7 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, >200-<=400 Gi/L, n=139, 135 | 3 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, <50 Gi/L, n=147, 145 | 136 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, >=50-<=80 Gi/L, n=147, 145 | 8 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, >80-<=200 Gi/L, n=147, 145 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, >200-<=400 Gi/L, n=147, 145 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Screening, >400 Gi/L, n=147, 145 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, <50 Gi/L, n=139, 135 | 48 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, >=50-<=80 Gi/L, n=139, 135 | 50 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, >80-<=200 Gi/L, n=139, 135 | 33 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 8, >400 Gi/L, n=139, 135 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, <50 Gi/L, n=132, 131 | 14 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, >=50-<=80 Gi/L, n=132, 131 | 31 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, >80-<=200 Gi/L, n=132, 131 | 67 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, >200-<=400 Gi/L, n=132, 131 | 19 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Day 15, >400 Gi/L, n=132, 131 | 0 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, <50 Gi/L, n=128, 126 | 11 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, >=50-<=80 Gi/L, n=128, 126 | 20 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, >80-<=200 Gi/L, n=128, 126 | 60 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, >200-<=400 Gi/L, n=128, 126 | 30 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 7 Day FU, >400 Gi/L, n=128, 126 | 4 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, <50 Gi/L, n=117, 125 | 22 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, >=50-<=80 Gi/L, n=117, 125 | 21 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, >80-<=200 Gi/L, n=117, 125 | 62 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, >200-<=400 Gi/L, n=117, 125 | 17 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 14 Day FU, >400 Gi/L, n=117, 125 | 3 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, <50 Gi/L, n=121, 117 | 38 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, >=50-<=80 Gi/L, n=121, 117 | 33 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, >80-<=200 Gi/L, n=121, 117 | 38 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, >200-<=400 Gi/L, n=121, 117 | 7 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Procedure + 21 Day FU, >400 Gi/L, n=121, 117 | 1 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, <50 Gi/L, n=144, 140 | 11 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, >=50-<=80 Gi/L, n=144, 140 | 23 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, >80-<=200 Gi/L, n=144, 140 | 62 participants |
| Eltrombopag 75 mg | Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline | Maximum Post-Baseline, >200-<=400 Gi/L, n=144, 140 | 37 participants |
Secondary
Pharmacokinetics (PK) of Eltrombopag, CL/F
CL/F is the apparent plasma clearance, where CL is an estimate of the total body clearance, and F is the fraction of dose absorbed. Total clearance is the volume of blood cleared of the drug by the various elimination processes (metabolism and excretion) per unit time.
Time frame: Day 14
Population: PK Subpopulation
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Pharmacokinetics (PK) of Eltrombopag, CL/F | 0.30 Liters/hour |
Secondary
Pharmacokinetics (PK) of Eltrombopag, Cmax
Cmax is the steady state peak plasma concentration of a drug observed after its administration.
Time frame: Day 14
Population: PK Subpopulation
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Pharmacokinetics (PK) of Eltrombopag, Cmax | 11.6 ug/mL |
Secondary
Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau)
AUC(0-tau) is the area under a concentration versus time curve between dose interval following repeat dosing. It is a measure of systemic drug exposure.
Time frame: Day 14
Population: PK Subpopulation: all participants who were treated with eltrombopag and provided evaluable PK samples
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau) | 250 hour*micrograms (ug)/milliliter (mL) |
Secondary
Pharmacokinetics (PK) of Eltrombopag, t1/2
t1/2 is the half life of a drug based on its terminal phase. Half life is defined as the time necessary to halve the plasma concentration.
Time frame: Day 14
Population: PK Subpopulation
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Pharmacokinetics (PK) of Eltrombopag, t1/2 | 70.3 hours |