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

History of Changes

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

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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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

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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.

[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

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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 information, such as adjustments or degrees of freedom:
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[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4]	Other relevant estimation information:
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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:
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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 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

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

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.

Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided by GlaxoSmithKline

Publications automatically indexed to this study:

Afdhal NH, Giannini EG, Tayyab G, Mohsin A, Lee JW, Andriulli A, Jeffers L, McHutchison J, Chen PJ, Han KH, Campbell F, Hyde D, Brainsky A, Theodore D; ELEVATE Study Group. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med. 2012 Aug 23;367(8):716-24.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00678587 History of Changes
Other Study ID Numbers:	TPL104054
Study First Received:	May 13, 2008
Results First Received:	October 10, 2010
Last Updated:	February 7, 2013
Health Authority:	European Union: European Medicines Agency United States: Food and Drug Administration

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