Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures (ELEVATE)

This study has been terminated.
(GSK decision)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00678587
First received: May 13, 2008
Last updated: February 7, 2013
Last verified: January 2013
Results First Received: October 10, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Non-alcoholic Steatohepatitis
Chronic Liver Disease
HCV
NASH.
HIV Infection
Thrombocytopenia
Hepatitis C Virus
HBV
Human Immunodeficiency Virus
Liver Diseases
Hepatitis B Virus
Interventions: Drug: Eltrombopag
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Participant Flow:   Overall Study
    Placebo     Eltrombopag 75 mg  
STARTED     147     145  
COMPLETED     127     127  
NOT COMPLETED     20     18  
Adverse Event                 3                 3  
Lack of Efficacy                 1                 0  
Protocol Violation                 2                 1  
Study Closed/Terminated                 1                 0  
Lost to Follow-up                 3                 5  
Investigator Discretion                 2                 6  
Withdrew Consent                 8                 3  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily
Total Total of all reporting groups

Baseline Measures
    Placebo     Eltrombopag 75 mg     Total  
Number of Participants  
[units: participants]
  147     145     292  
Age  
[units: Years]
Mean ± Standard Deviation
  53.5  ± 11.78     51.6  ± 11.04     52.5  ± 11.44  
Gender  
[units: Participants]
     
Female     55     49     104  
Male     92     96     188  
Race/Ethnicity, Customized  
[units: participants]
     
White     93     85     178  
Central/South Asian Heritage     33     41     74  
Japanese/East Asian/South East Asian Heritage     19     14     33  
African American/African Heritage     2     4     6  
Native Hawaiian/Other Pacific Islander and White     0     1     1  
Number of participants categorized into the indicated Child-Pugh (CP) Class [1]
[units: participants]
     
Child-Pugh Class A     59     68     127  
Child-Pugh Class B     64     57     121  
Child-Pugh Class C     17     10     27  
Model for End-Stage Liver Disease (MELD) Score at Baseline [2]
[units: scores on a scale]
Median ( Full Range )
  12  
  ( 6 to 25 )  
  12  
  ( 6 to 24 )  
  12  
  ( 6 to 25 )  
[1] The CP score (ranging from 5 to 15; 5=mild, 15=severe), calculated based on total bilirubin, serum albumin, international normalized ratio, ascites, and hepatic encephalopathy, is used to assess liver disease severity. 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. The number of participants analyzed is 140 for placebo and 135 for Eltrombopag; not all participants were compliant and had their baseline CP score measured.
[2] MELD uses the following formula to calculate a participant’s likelihood of dying within 3 months from liver disease: 3.8 x log (e) (bilirubin milligrams [mg]/deciliter [dL]) + 11.2 x log (e) (international ratio for prothrombin time) + 9.6 log (e) (creatinine mg/dL). Scores range from 6 (least ill) to 40 (most ill): 40 or more, 71.3% mortality; 30-39, 52.6% mortality; 20-29, 19.6% mortality; 10-19, 6.0% mortality; <9, 1.9% mortality. The number of participants analyzed is 140 for placebo and 135 for Eltrombopag; not all participants were compliant and had their baseline MELD score measured.



  Outcome Measures
  Hide All Outcome Measures

1.  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   [ 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 ]

Measure Type Primary
Measure Title 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
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all participants who were randomized to treatment

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  147     145  
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  
[units: participants]
  28     104  


Statistical Analysis 1 for 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
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.0001
Absolute difference in proportions [4] 52.8
95% Confidence Interval ( 43.2 to 62.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures   [ 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 ]

Measure Type Secondary
Measure Title Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  147     145  
Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures  
[units: participants]
  34     25  


Statistical Analysis 1 for Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures
Groups [1] All groups
Risk Difference (RD) [2] -5.9
95% Confidence Interval ( -15.1 to 3.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  No text entered.



3.  Secondary:   Number of Participants With the Indicated Number of Platelet Transfusions Administered   [ 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 ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Number of Platelet Transfusions Administered
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  147     145  
Number of Participants With the Indicated Number of Platelet Transfusions Administered  
[units: participants]
   
0     30     106  
1     93     24  
2     3     1  
3     2     0  
4     3     0  
5     0     0  
6     1     0  
Died/withdrew prior to any platelet transfusions     15     14  


Statistical Analysis 1 for Number of Participants With the Indicated Number of Platelet Transfusions Administered
Groups [1] All groups
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] <0.0001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



4.  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   [ Time Frame: Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 day follow-up; early withdrawal; and maximum post-baseline ]

Measure Type Secondary
Measure Title 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
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. The number of participants analyzed decreases over time due to missing measurements and to participants dropping out of the study.

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  147     145  
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  
[units: Gi/L]
Median ( Full Range )
   
Screening, n=147, 145     40.0  
  ( 8 to 70 )  
  40.0  
  ( 3 to 55 )  
Day 1, n=145, 141     40.0  
  ( 8 to 222 )  
  40.0  
  ( 12 to 62 )  
Day 8, n=139, 134     41.0  
  ( 6 to 190 )  
  58.5  
  ( 20 to 337 )  
Day 15, n=132, 131     39.0  
  ( 6 to 200 )  
  103.0  
  ( 25 to 397 )  
Days 16-19, n=50, 49     41.5  
  ( 18 to 250 )  
  107.0  
  ( 30 to 406 )  
Procedure + 7 day follow-up, n=128, 125     44.0  
  ( 17 to 150 )  
  148  
  ( 30 to 493 )  
Procedure + 14 day follow-up, n=116, 125     47.5  
  ( 13 to 370 )  
  110  
  ( 18 to 805 )  
Procedure + 21 day follow-up, n=120, 117     44.5  
  ( 11 to 200 )  
  62.0  
  ( 15 to 967 )  
Procedure + 30 day follow-up, n=125, 127     40.0  
  ( 10 to 200 )  
  50.0  
  ( 14 to 999 )  
Early withdrawal, n=9, 8     40.0  
  ( 11 to 195 )  
  41.0  
  ( 32 to 140 )  
Maximum post-baseline, n=144, 140     53.0  
  ( 16 to 370 )  
  152  
  ( 32 to 999 )  

No statistical analysis provided for 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



5.  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   [ Time Frame: Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 day follow-up; and maximum post-baseline ]

Measure Type Secondary
Measure Title 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
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. The number of participants analyzed decreases over time due to missing measurements and to participants dropping out of the study.

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  147     145  
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  
[units: participants]
   
Screening, <50 Gi/L, n=147, 145     133     136  
Screening, >=50-<=80 Gi/L, n=147, 145     14     8  
Screening, >80-<=200 Gi/L, n=147, 145     0     0  
Screening, >200-<=400 Gi/L, n=147, 145     0     0  
Screening, >400 Gi/L, n=147, 145     0     0  
Day 8, <50 Gi/L, n=139, 135     98     48  
Day 8, >=50-<=80 Gi/L, n=139, 135     34     50  
Day 8, >80-<=200 Gi/L, n=139, 135     7     33  
Day 8, >200-<=400 Gi/L, n=139, 135     0     3  
Day 8, >400 Gi/L, n=139, 135     0     0  
Day 15, <50 Gi/L, n=132, 131     98     14  
Day 15, >=50-<=80 Gi/L, n=132, 131     26     31  
Day 15, >80-<=200 Gi/L, n=132, 131     8     67  
Day 15, >200-<=400 Gi/L, n=132, 131     0     19  
Day 15, >400 Gi/L, n=132, 131     0     0  
Procedure + 7 Day FU, <50 Gi/L, n=128, 126     78     11  
Procedure + 7 Day FU, >=50-<=80 Gi/L, n=128, 126     38     20  
Procedure + 7 Day FU, >80-<=200 Gi/L, n=128, 126     12     60  
Procedure + 7 Day FU, >200-<=400 Gi/L, n=128, 126     0     30  
Procedure + 7 Day FU, >400 Gi/L, n=128, 126     0     4  
Procedure + 14 Day FU, <50 Gi/L, n=117, 125     63     22  
Procedure + 14 Day FU, >=50-<=80 Gi/L, n=117, 125     40     21  
Procedure + 14 Day FU, >80-<=200 Gi/L, n=117, 125     11     62  
Procedure + 14 Day FU, >200-<=400 Gi/L, n=117, 125     2     17  
Procedure + 14 Day FU, >400 Gi/L, n=117, 125     0     3  
Procedure + 21 Day FU, <50 Gi/L, n=121, 117     80     38  
Procedure + 21 Day FU, >=50-<=80 Gi/L, n=121, 117     30     33  
Procedure + 21 Day FU, >80-<=200 Gi/L, n=121, 117     10     38  
Procedure + 21 Day FU, >200-<=400 Gi/L, n=121, 117     0     7  
Procedure + 21 Day FU, >400 Gi/L, n=121, 117     0     1  
Maximum Post-Baseline, <50 Gi/L, n=144, 140     60     11  
Maximum Post-Baseline, >=50-<=80 Gi/L, n=144, 140     53     23  
Maximum Post-Baseline, >80-<=200 Gi/L, n=144, 140     28     62  
Maximum Post-Baseline, >200-<=400 Gi/L, n=144, 140     3     37  
Maximum Post-Baseline, >400 Gi/L, n=144, 140     0     7  

No statistical analysis provided for 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



6.  Secondary:   Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category   [ Time Frame: Screening to Procedure +30 day follow-up or early withdrawal ]

Measure Type Secondary
Measure Title Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population: all randomized participants who received at least one dose of study medication

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  145     142  
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category  
[units: participants]
   
AEs during study     85     79  
Drug-related AEs in >1 participant     15     31  
Throboembolic AEs     2     6  
Bleeding AEs     25     19  
Hepatobiliary AEs     16     24  
Malignancy AEs     1     1  
Renal AEs     4     2  
Death on study     2     3  
SAEs in >1 participant during study     17     19  
Drug-related SAEs in >1 participant     4     9  
Thrombocytopenia     1     1  
Progression of pre-existing cataract n=145,143     2     0  
Incident cataract develpment n=145,143     2     4  
Decrease in visual acuity n=121,124     19     21  
Renal function abnormality n=145,143     27     28  
Clinically significant change in ECG n=128,130     0     1  

No statistical analysis provided for Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category



7.  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 ]

Measure Type Secondary
Measure Title Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant
Measure Description No text entered.
Time Frame Screening to Procedure +30 day follow-up or early withdrawal  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Population

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  145     143  
Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant  
[units: participants]
  4     9  

No statistical analysis provided for Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant



8.  Secondary:   Number of Participants With the Indicated Event Relating to Vision   [ Time Frame: Screening or Baseline and at End of Study (Procedure +30 day follow-up or withdrawal visit) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Event Relating to Vision
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Population: all randomized participants who received at least one dose of study medication. Data are missing for some participants.

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  145     143  
Number of Participants With the Indicated Event Relating to Vision  
[units: participants]
   
Progression of pre-existing cataract, n=145, 143     2     0  
Cataract development, n=145, 143     2     4  
Decrease in visual acuity, n=121, 124     19     21  

No statistical analysis provided for Number of Participants With the Indicated Event Relating to Vision



9.  Secondary:   Number of Participants With Renal Function Abnormality   [ Time Frame: Screening to Procedure +30 day follow-up or early withdrawal ]

Measure Type Secondary
Measure Title Number of Participants With Renal Function Abnormality
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Population

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  145     143  
Number of Participants With Renal Function Abnormality  
[units: participants]
  27     28  

No statistical analysis provided for Number of Participants With Renal Function Abnormality



10.  Secondary:   Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results   [ Time Frame: Screening, Baseline, Day 15, and Withdrawal ]

Measure Type Secondary
Measure Title Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Population. Data were missing for some participants.

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  128     130  
Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results  
[units: participants]
  0     1  

No statistical analysis provided for Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results



11.  Secondary:   Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau)   [ Time Frame: Day 14 ]

Measure Type Secondary
Measure Title Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau)
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Subpopulation: all participants who were treated with eltrombopag and provided evaluable PK samples

Reporting Groups
  Description
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  41  
Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau)  
[units: hour*micrograms (ug)/milliliter (mL)]
Geometric Mean ( 95% Confidence Interval )
  250  
  ( 211 to 296 )  

No statistical analysis provided for Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau)



12.  Secondary:   Pharmacokinetics (PK) of Eltrombopag, Cmax   [ Time Frame: Day 14 ]

Measure Type Secondary
Measure Title Pharmacokinetics (PK) of Eltrombopag, Cmax
Measure Description Cmax is the steady state peak plasma concentration of a drug observed after its administration.
Time Frame Day 14  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Subpopulation

Reporting Groups
  Description
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  41  
Pharmacokinetics (PK) of Eltrombopag, Cmax  
[units: ug/mL]
Geometric Mean ( 95% Confidence Interval )
  11.6  
  ( 9.8 to 13.6 )  

No statistical analysis provided for Pharmacokinetics (PK) of Eltrombopag, Cmax



13.  Secondary:   Pharmacokinetics (PK) of Eltrombopag, t1/2   [ Time Frame: Day 14 ]

Measure Type Secondary
Measure Title Pharmacokinetics (PK) of Eltrombopag, t1/2
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Subpopulation

Reporting Groups
  Description
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  41  
Pharmacokinetics (PK) of Eltrombopag, t1/2  
[units: hours]
Geometric Mean ( 95% Confidence Interval )
  70.3  
  ( 60.7 to 81.5 )  

No statistical analysis provided for Pharmacokinetics (PK) of Eltrombopag, t1/2



14.  Secondary:   Pharmacokinetics (PK) of Eltrombopag, CL/F   [ Time Frame: Day 14 ]

Measure Type Secondary
Measure Title Pharmacokinetics (PK) of Eltrombopag, CL/F
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Subpopulation

Reporting Groups
  Description
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  41  
Pharmacokinetics (PK) of Eltrombopag, CL/F  
[units: Liters/hour]
Geometric Mean ( 95% Confidence Interval )
  0.30  
  ( 0.25 to 0.36 )  

No statistical analysis provided for Pharmacokinetics (PK) of Eltrombopag, CL/F



15.  Secondary:   Mean Number of Days Spent in the Hospital   [ 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 ]

Measure Type Secondary
Measure Title Mean Number of Days Spent in the Hospital
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Data are missing for some participants.

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  144     144  
Mean Number of Days Spent in the Hospital  
[units: days]
Mean ± Standard Deviation
  1.3  ± 3.77     1.7  ± 6.43  

No statistical analysis provided for Mean Number of Days Spent in the Hospital



16.  Secondary:   Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures   [ 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 ]

Measure Type Secondary
Measure Title Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Data are missing for some participants.

Reporting Groups
  Description
Placebo Matching placebo
Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily

Measured Values
    Placebo     Eltrombopag 75 mg  
Number of Participants Analyzed  
[units: participants]
  144     144  
Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures  
[units: unscheduled events]
Mean ± Standard Deviation
   
Unscheduled office visits     0.8  ± 1.64     1.0  ± 2.91  
Unscheduled laboratory tests     1.1  ± 3.78     1.8  ± 5.67  
Unscheduled procedures     0.3  ± 0.81     0.4  ± 1.65  

No statistical analysis provided for Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information