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Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Subjects With Hepatitis C Related Liver Disease

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ClinicalTrials.gov Identifier: NCT00516321
Recruitment Status : Completed
First Posted : August 15, 2007
Results First Posted : July 30, 2012
Last Update Posted : November 5, 2013
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hepatitis C, Chronic
Interventions Drug: eltrombopag
Drug: placebo
Enrollment 687
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Eltrombopag: OL Phase Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description Participants with a platelet count of <75 giga (10^9) cells per liter (Gi/L) initially received eltrombopag 25 milligrams (mg) once daily (QD) for 2 weeks. After 2 weeks, if the platelet count was <90 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained <90 Gi/L, further dose escalations to 75 mg QD (up to 2 weeks) and 100 mg QD (up to a maximum of 3 weeks) were allowed. Participants who achieved platelet counts >=90 Gi/L during the OL Phase (maximum of up to 9 weeks) were eligible to enter the Double-blind (DB) Antiviral Treatment Phase, whereas those who failed to reach platelet counts >=90 Gi/L were discontinued from eltrombopag and had to attend the post-treatment follow-up visits. Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3). Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Period Title: Open-label (OL) Pre-Antiviral Treatment
Started 715 0 0
Completed 682 0 0
Not Completed 33 0 0
Reason Not Completed
Lack of Efficacy             11             0             0
Adverse Event             9             0             0
Protocol Violation             1             0             0
Lost to Follow-up             2             0             0
Investigator Discretion             7             0             0
Withdrawal by Subject             3             0             0
Period Title: Double-blind (DB) Antiviral Treatment
Started 0 232 450
Completed 0 197 396
Not Completed 0 35 54
Reason Not Completed
Lost to Follow-up             0             12             22
Withdrawal by Subject             0             13             18
Adverse Event             0             8             13
Protocol Violation             0             0             1
Physician Decision             0             2             0
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase Total
Hide Arm/Group Description Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3). Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3). Total of all reporting groups
Overall Number of Baseline Participants 232 450 682
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Years Number Analyzed 232 participants 450 participants 682 participants
51.4  (8.52) 52.1  (8.35) 51.9  (8.41)
[1]
Measure Description: Baseline characteristics were collected for the Intent-to-Treat (ITT) Population, which included all randomized participants in the Double-blind (DB) Phase of the study.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 232 participants 450 participants 682 participants
Female
73
  31.5%
186
  41.3%
259
  38.0%
Male
159
  68.5%
264
  58.7%
423
  62.0%
[1]
Measure Description: Baseline characteristics were collected for the Intent-to-Treat (ITT) Population, which included all randomized participants in the Double-blind (DB) Phase of the study.
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 232 participants 450 participants 682 participants
African American/African Heritage 6 12 18
American Indian/Alaska Native 3 2 5
Central/South Asian Heritage 14 39 53
Japanese/East Asian Heritage/South East Asian 43 68 111
Native Hawaiian or Other Pacific Islander 0 1 1
White 166 326 492
Asian and White 0 1 1
Native Hawaiian/ Other Pacific Islander and White 0 1 1
[1]
Measure Description: Baseline characteristics were collected for the ITT Population, which included all randomized participants in the DB Phase of the study.
Number of participants categorized into the indicated genotype for Hepatitic C Virus (HCV)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 232 participants 450 participants 682 participants
Genotype 1 149 292 441
Genotype 2 22 27 49
Genotype 3 54 115 169
Genotype 4 5 11 16
Genotype 5 0 0 0
Genotype 6 2 4 6
Genotype 7 0 0 0
Missing Data 0 1 1
[1]
Measure Description: Baseline characteristics were collected for the ITT Population, which included all randomized participants in the DB Phase of the study. The HCV is a small, enveloped, single-stranded, positive-sense ribonucleic acid (RNA) virus. There are seven major genotypes of HCV, which are indicated numerically from Genotype 1 to 7.
Number of participants categorized into the indicated Child-Pugh (CP) Class   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 232 participants 450 participants 682 participants
Class A 217 424 641
Class B 15 25 40
Class C 0 0 0
Missing Data 0 1 1
[1]
Measure Description: The CP score (ranging from 5 to 15, with 5 being mild and 15 being severe), calculated based on total bilirubin, serum albumin, international normalized ratio, ascites, and hepatic encephalopathy, is used to assess the severity of liver disease. A CP score of 5-6 = Class A (mild); 7-9 = Class B (moderate); >=10 = Class C (severe).
Number of participants with or without previous interferon (IFN) use   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 232 participants 450 participants 682 participants
Naïve 152 307 459
Experienced 80 143 223
[1]
Measure Description: Baseline characteristics were collected for the ITT Population, which included all randomized participants in the DB Phase of the study. Participants at Baseline were classified as not having used IFN previously (Naïve) or having used IFN previously (Experienced).
Number of participants with the indicated FibroTest/Acti Test (FibroSURE) score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 232 participants 450 participants 682 participants
Score: F0/F1/F2 23 37 60
Score: F3/F4 185 354 539
Missing 24 59 83
[1]
Measure Description: FibroSURE is a noninvasive blood test that combines the quantitative results of 6 serum biochemical markers (α2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, γ-glutamyl transpeptidase [GGT], and ALT) with a participant's age and gender to generate a measure of liver fibrosis/cirrhosis and necroinflammatory activity. It provides a numerical quantitative estimate of liver fibrosis ranging from 0.00 to 1.00, corresponding to the Metavir scoring system of stages F0 to F4 (F0, no fibrosis [F]; F1, portal F; F2, bridging F with few septa; F3, bridging F with many septa; F4=cirrhosis).
Number of participants with normal or elevated Baseline values for Alanine Aminotransferase (ALT)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 232 participants 450 participants 682 participants
Normal 54 103 157
Elevated 178 347 525
[1]
Measure Description: Baseline characteristics were collected for the ITT Population, which included all randomized participants in the DB Phase of the study. The normal range of ALT is 0 to 48 International Units per Liter (IU/L).
Baseline HCV Ribonucleic Acid (RNA)   [1] 
Mean (Standard Deviation)
Unit of measure:  International Units per milliliter
Number Analyzed 232 participants 450 participants 682 participants
1880278.4  (3395777.02) 1870562.1  (3080918.03) 1873862.8  (3188864.74)
[1]
Measure Description: Baseline characteristics were collected for the ITT Population, which included all randomized participants in the DB Phase of the study. HCV RNA was assessed at baseline of the DB Phase. Data are missing for one participant in the Eltrombopag+Antiviral Therapy treatment group.
Baseline Platelet Count   [1] 
Mean (Standard Deviation)
Unit of measure:  Giga (10^9) cells per liter (Gi/L)
Number Analyzed 232 participants 450 participants 682 participants
57.40  (12.890) 56.87  (13.603) 57.05  (13.357)
[1]
Measure Description: Baseline characteristics were collected for the ITT Population, which included all randomized participants in the DB Phase of the study. Platelet count eligibility was confirmed at the Baseline visit, prior to administration of eltrombopag, and was defined as the average of the screening and baseline counts, which must be <75 Gi/L.
1.Primary Outcome
Title Number of Participants With Sustained Virologic Response (SVR) in the Double-blind (DB) Antiviral Treatment Phase
Hide Description Participants with SVR were defined as those with undetectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) at 24 weeks post-completion of the treatment period of the DB Phase.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized in the DB Phase
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 450
Measure Type: Number
Unit of Measure: participants
33 104
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo+Antiviral Therapy: DB Phase, Eltrombopag+Antiviral Therapy: DB Phase
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0064
Comments Stratified Cochran-Mantel-Haenszel (CMH) chi-square test adjusted for the randomization strata
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage difference in SVR
Estimated Value 7.9
Confidence Interval (2-Sided) 95%
2.4 to 13.4
Estimation Comments The estimated value reflects the percentage of participants with SVR in the eltrombopag group minus the percentage of participants with SVR in the placebo group. Adjusted for the actual strata: HCV genotype, baseline platelet count, and HCV RNA.
2.Secondary Outcome
Title Number of Participants Whose Platelet Count Increased From a Baseline Count of <75 Gi/L to a Count Greater Than or Equal to (>=) 90 Giga (10^9) Cells Per Liter (Gi/L) During the Open-label (OL) Pre-Antiviral Treatment Phase
Hide Description Participants were assessed for a shift from a baseline platelet count of <75 Gi/L to a count >=90 Gi/L during the OL Phase (up to 9 weeks). Local laboratories were used for platelet function tests. Platelet counts were measured by blood draw.
Time Frame From Baseline up to Week 9 in the OL Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who had received study drug in the OL Phase
Arm/Group Title Eltrombopag: OL Phase
Hide Arm/Group Description:
Participants with a platelet count of <75 giga (10^9) cells per liter (Gi/L) initially received eltrombopag 25 milligrams (mg) once daily (QD) for 2 weeks. After 2 weeks, if the platelet count was <90 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained <90 Gi/L, further dose escalations to 75 mg QD (up to 2 weeks) and 100 mg QD (up to a maximum of 3 weeks) were allowed. Participants who achieved platelet counts >=90 Gi/L during the OL Phase (maximum of up to 9 weeks) were eligible to enter the Double-blind (DB) Antiviral Treatment Phase, whereas those who failed to reach platelet counts >=90 Gi/L were discontinued from eltrombopag and had to attend the post-treatment follow-up visits.
Overall Number of Participants Analyzed 715
Measure Type: Number
Unit of Measure: participants
691
3.Secondary Outcome
Title Number of Participants Receiving the Indicated Doses of Eltrombopag in the OL Phase Who Initiated Antiviral Therapy (Peginterferon Alfa-2a and Ribavirin) in the DB Phase
Hide Description In the OL Phase, participants initially received the lowest dose of eltrombopag (25 mg QD) for 2 weeks. If after this time the platelet count was <90 Gi/L, participants underwent sequential dose escalation to the next highest dose (50 mg QD for up to 2 weeks), with further dose escalations to 75 mg QD (up to 2 weeks) and 100 mg QD (up to a maximum of 3 weeks) if platelet counts remained <90 Gi/L. Participants who achieved platelet count >=90 Gi/L on any of the eltrombopag doses in the OL Phase initiated antiviral therapy in the DB Phase.
Time Frame From Baseline up to Week 9 in the OL Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Participants with a platelet count >=90 Gi/L and who initiated antiviral therapy during the DB Phase were analyzed.
Arm/Group Title Eltrombopag: OL Phase
Hide Arm/Group Description:
Participants with a platelet count of <75 giga (10^9) cells per liter (Gi/L) initially received eltrombopag 25 milligrams (mg) once daily (QD) for 2 weeks. After 2 weeks, if the platelet count was <90 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained <90 Gi/L, further dose escalations to 75 mg QD (up to 2 weeks) and 100 mg QD (up to a maximum of 3 weeks) were allowed. Participants who achieved platelet counts >=90 Gi/L during the OL Phase (maximum of up to 9 weeks) were eligible to enter the Double-blind (DB) Antiviral Treatment Phase, whereas those who failed to reach platelet counts >=90 Gi/L were discontinued from eltrombopag and had to attend the post-treatment follow-up visits.
Overall Number of Participants Analyzed 680
Measure Type: Number
Unit of Measure: participants
25 mg 451
50 mg 176
75 mg 39
100 mg 14
4.Secondary Outcome
Title Median Platelet Count at the Indicated Time Points During the OL Phase
Hide Description Blood taken from peripheral blood vessels was used for the measurement of platelet counts. The Last On Treatment assessment refers to the actual last treatment assessment, not necessarily to the End of Treatment assessment entered by the Investigator.
Time Frame OL Phase: Baseline; Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, and 9; Antiviral Baseline (up to Week 10); End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 62); 12-week FU (up to Week 70); and 24-week FU (up to Week 82)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants contributing data at the indicated time points were analyzed.
Arm/Group Title Eltrombopag: OL Phase
Hide Arm/Group Description:
Participants with a platelet count of <75 giga (10^9) cells per liter (Gi/L) initially received eltrombopag 25 milligrams (mg) once daily (QD) for 2 weeks. After 2 weeks, if the platelet count was <90 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained <90 Gi/L, further dose escalations to 75 mg QD (up to 2 weeks) and 100 mg QD (up to a maximum of 3 weeks) were allowed. Participants who achieved platelet counts >=90 Gi/L during the OL Phase (maximum of up to 9 weeks) were eligible to enter the Double-blind (DB) Antiviral Treatment Phase, whereas those who failed to reach platelet counts >=90 Gi/L were discontinued from eltrombopag and had to attend the post-treatment follow-up visits.
Overall Number of Participants Analyzed 712
Median (Full Range)
Unit of Measure: Gi/L
Baseline, n=712
59.00
(3.00 to 98.34)
Day 1, n=620
59.00
(5.00 to 108.00)
Week 1, n=703
77.00
(7.00 to 226.00)
Week 2, n=426
89.00
(11.00 to 389.58)
Week 3, n=179
83.00
(11.00 to 335.00)
Week 4, n=98
83.00
(12.00 to 310.00)
Week 5, n=56
77.00
(16.00 to 379.00)
Week 6, n=35
79.00
(24.00 to 436.00)
Week 7, n=29
77.00
(30.00 to 187.90)
Week 8, n=18
83.00
(37.00 to 135.00)
Week 9, n=7
70.00
(38.00 to 113.00)
Antiviral Baseline, n=48
130.00
(90.00 to 291.00)
End of Treatment/Withdrawal, n=18
63.00
(6.00 to 331.97)
Last on Treatment, n=30
75.00
(6.00 to 249.56)
4 Week Follow-Up, n=15
44.00
(4.00 to 248.85)
12 Week Follow-Up, n=16
38.00
(19.00 to 86.00)
24 Week Follow-Up, n=15
38.00
(9.00 to 79.00)
5.Secondary Outcome
Title Median Platelet Count at the Indicated Time Points During the DB Phase
Hide Description Blood taken from peripheral blood vessels was used for the measurement of platelet counts.
Time Frame DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants contributing data at the indicated time points were analyzed. The Last On Treatment assessment refers to the actual last treatment assessment, not necessarily to the End of Treatment assessment entered by the Investigator.
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 447
Median (Full Range)
Unit of Measure: Gi/L
Baseline, n=208, 387
128.00
(84.00 to 521.00)
133.00
(64.00 to 509.00)
Week 1, n=227, 443
112.00
(30.00 to 398.00)
115.00
(31.00 to 502.00)
Week 2, n=227, 438
79.00
(25.00 to 297.00)
111.00
(36.00 to 596.00)
Week 4, n=218, 430
43.50
(17.00 to 275.00)
90.00
(5.00 to 430.00)
Week 6, n=197, 423
40.00
(12.00 to 261.00)
89.00
(22.00 to 315.00)
Week 8, n=189, 414
41.00
(15.00 to 320.00)
86.00
(22.00 to 249.00)
Week 12, n=165, 404
44.00
(16.00 to 284.00)
91.50
(25.00 to 298.00)
Week 16, n=141, 377
43.00
(16.00 to 280.00)
93.00
(26.00 to 376.00)
Week 20, n=135, 363
44.00
(18.00 to 325.00)
89.00
(25.00 to 339.00)
Week 24, n=89, 248
43.00
(21.00 to 333.00)
92.00
(18.00 to 276.00)
Week 28, n=73, 202
45.00
(22.00 to 345.00)
89.50
(17.00 to 207.00)
Week 32, n=69, 183
44.40
(24.00 to 338.00)
91.00
(21.00 to 406.00)
Week 36, n=68, 173
44.50
(16.00 to 315.00)
91.00
(21.00 to 209.00)
Week 40, n=64, 169
44.00
(22.00 to 276.00)
93.00
(30.00 to 226.00)
Week 44, n=65, 168
48.00
(22.00 to 320.00)
93.50
(27.00 to 238.00)
End of Treatment/Withdrawal, n=212, 419
40.00
(8.00 to 318.00)
90.00
(5.00 to 420.00)
Last on Treatment, n=232, 447
40.00
(8.00 to 318.00)
90.00
(5.00 to 420.00)
4 Week Follow-Up, n=205, 400
54.00
(5.00 to 358.00)
82.00
(5.00 to 304.00)
12 Week Follow-Up, n=196, 396
56.00
(8.00 to 311.00)
67.00
(1.00 to 350.00)
24 Week Follow-Up, n=193, 391
56.00
(9.00 to 433.00)
60.00
(7.00 to 340.00)
6.Secondary Outcome
Title Number of Participants in the Indicated Categories for Minimum Platelet Count With Antiviral Therapy During the DB Phase
Hide Description The minimum platelet count with antiviral therapy was categorized as follows: <25 Gi/L; >=25 to <50 Gi/L; >=50 to <90 Gi/L; >=90 to <150 Gi/L; >=150 Gi/L to <200 Gi/L; >=200 Gi/L to <400 Gi/L; and >=400 Gi/L.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 450
Measure Type: Number
Unit of Measure: participants
<25 Gi/L 63 12
>=25 to <50 Gi/L 135 125
>=50 to <90 Gi/L 19 245
>=90 to <150 Gi/L 11 58
>=150 to <200 Gi/L 2 6
>=200 to <400 Gi/L 2 1
>=400 Gi/L 0 0
Missing 0 3
7.Secondary Outcome
Title Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) During the DB Phase
Hide Description RVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment. eRVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment that persisted through Week 12.
Time Frame From Baseline up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 450
Measure Type: Number
Unit of Measure: participants
RVR 39 73
eRVR 28 68
8.Secondary Outcome
Title Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) During the DB Phase
Hide Description EVR is defined as a clinically significant reduction from Baseline in HCV RNA (>=2 log10 decrease in HCV RNA or undetectable HCV RNA) after 12 weeks of antiviral treatment. cEVR, a subset of EVR, is defined exclusively as undetectable HCV RNA after 12 weeks of antiviral treatment.
Time Frame From Baseline up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 450
Measure Type: Number
Unit of Measure: participants
EVR 115 297
cEVR 60 187
9.Secondary Outcome
Title Number of Participants With End of Treatment Response (ETR) and Sustained Virological Response at Week 12 of Follow-up (SVR12) During the DB Phase
Hide Description ETR is defined as the absence of detectable HCV RNA at the end of antiviral treatment. SVR12 is defined as the absence of detectable HCV RNA at the end of antiviral treatment and the 12-week follow-up assessment.
Time Frame From Baseline up to Week 36 or Week 60 (for participants with Genotype 2/3) or up to Week 60 (for participants with Non-Genotype 2/3)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 450
Measure Type: Number
Unit of Measure: participants
ETR 86 214
SVR12 36 347
10.Secondary Outcome
Title Number of Participants in the Indicated Categories for Antiviral Therapy Dose Reductions in the DB Phase
Hide Description Participants were assigned a score equal to the number of times their dose of antiviral therapy (peginterferon or ribavirin) was reduced (0=no dose reductions [DRs]; 1=one DR; 2=two DRs; 3=three DRs; >3=more than three DRs). Where possible, every effort was made to maintain the recommended dose of antiviral therapy for the treatment duration in the DB Phase. However, where dose modification of antiviral therapy was required due to safety concerns, it was performed by the Investigator as per the region-specific product labels of peginterferon and ribavirin.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
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Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 450
Measure Type: Number
Unit of Measure: participants
0 65 195
1 57 93
2 55 56
3 26 49
>3 29 57
11.Secondary Outcome
Title Time to First Dose Reduction of Peginterferon Alfa-2a and Ribavirin Therapy in the DB Phase
Hide Description Time to first dose reduction was calculated as the time period from the first dose to the first dose reduction.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
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Hide Analysis Population Description
ITT Population. Only those participants with dose reductions were analyzed.
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 163 193
Mean (Standard Deviation)
Unit of Measure: weeks
Peginterferon alfa-2a dose reduction, n=163, 193 5.81  (5.304) 9.04  (9.371)
Ribavirin dose reduction, n=63, 162 11.16  (9.219) 12.58  (9.830)
12.Secondary Outcome
Title Number of Participants With the Indicated Levels of Peginterferon Dose Reductions in the DB Phase
Hide Description The assigned dose in the DB Phase of peginterferon alfa-2a was 180 micrograms (mcg). For peginterferon dose modification, downward adjustments in one level increments was considered. The lowest dose of peginterferon alfa-2a that was allowed to be administered was 45 mcg. Where dose adjustment was required for moderate to severe adverse reactions (clinical and/or laboratory), an initial dose reduction to 135 mcg was generally adequate. In some cases, a dose reduction to 90 mcg or 45mcg was necessary. Dose increases toward the original dose were considered when the adverse reaction was resolved.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
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Hide Analysis Population Description
ITT Population. One participant could have had more than one dose reduction.
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 450
Measure Type: Number
Unit of Measure: participants
180 to 135 mcg 73 121
180 to 90 mcg 94 82
180 to 45 mcg 2 0
135 to 90 mcg 55 64
135 to 45 mcg 2 0
90 to 45 mcg 18 12
13.Secondary Outcome
Title Number of Participants Who Prematurely Discontinued Antiviral Therapy in the DB Phase
Hide Description The following participants were considered to have discontinued from antiviral therapy: participants who were lost to follow-up; participants who withdrew for any reason; participants who died; participants who otherwise did not complete their planned course of antiviral therapy for any reason. The planned duration of antiviral therapy was 48 weeks for participants with Non-Genotype 2/3 and 24 or 48 weeks for participants with Genotype 2/3.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 450
Measure Type: Number
Unit of Measure: participants
129 184
14.Secondary Outcome
Title Number of Participants (Par.) Categorized as Responders (R) and Non-responders (NR) for SVR and RVR to Antiviral Therapy in the Indicated Variants of Interleukin 28B (IL28B) (or Interferon, Lambda 3) During the DB Phase
Hide Description There are two genetic variants (rs12979860 and rs8099917) mapping near IL28B associated with both interferon-induced SVR and spontaneous HCV clearance. Genotyping of the IL28B polymorphisms (rs12979860 and rs8099917) was conducted. IL28B genotype distribution by response to antiviral therapy (SVR and RVR) for both treatment arms was assessed. The effect of genotype was tested by comparing participants that carried 2 copies of the IL28B favorable response allele versus the others (recessive model). Genotypes at rs12979860 were coded as: CC=1, CT or TT=0; rs8099917 was coded as TT=1, GT or GG=0.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
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Hide Analysis Population Description
Pharmacogenetic (PGx) Sub-Population: participants enrolled in this study who provided written informed consent for PGx research with a blood sample for genotyping and who were successfully genotyped for at least one of the two genetic markers under study
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 99 181
Measure Type: Number
Unit of Measure: participants
SVR, rs12979860 (CC), R; n=12, 36 5 18
SVR, rs12979860 (CC), NR; n=99, 168 21 38
SVR, rs12979860 (CT), R; n=12, 36 6 17
SVR, rs12979860 (CT), NR; n=99, 168 63 95
SVR, rs12979860 (TT), R; n=12, 36 1 1
SVR, rs12979860 (TT), NR; n=99, 168 15 35
SVR, rs8099917 (TT), R; n=12, 36 7 26
SVR, rs8099917 (TT), NR; n=99, 166 50 70
SVR, rs8099917 (GT), R; n=12, 36 4 9
SVR, rs8099917 (GT), NR; n=99, 166 42 75
SVR, rs8099917 (GG), R; n=12, 36 1 1
SVR, rs8099917 (GG), NR; n=99, 166 7 21
RVR, rs12979860 (CC), R; n=16, 23 7 12
RVR, rs12979860 (CC), NR; n=95, 181 19 44
RVR, rs12979860 (CT), R; n=16, 23 7 10
RVR, rs12979860 (CT), NR; n=95, 181 62 102
RVR, rs12979860 (TT), R; n=16, 23 2 1
RVR, rs12979860 (TT), NR; n=95, 181 14 35
RVR, rs8099917 (TT), R, n=16, 23 10 14
RVR, rs8099917 (TT), NR; n=95, 179 47 82
RVR, rs8099917 (GT), R; n=16, 23 4 9
RVR, rs8099917 (GT), NR; n=95, 179 42 75
RVR, rs8099917 (GG), R; n=16, 23 2 0
RVR, rs8099917 (GG), NR; n=95, 179 6 22
15.Secondary Outcome
Title Number of Par. With the Indicated Shift From Baseline (BL) in Severity Grades for Clinical Chemistry Parameters (Calcium, Glucose [Glu.], Potassium [Pot.], and Sodium [Sod.]), Per Division of Acquired Immunodeficiency Syndrome (DAIDS) During the DB Phase
Hide Description Blood samples for the assessment of clinical chemistry parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL during the DB Phase are reported, per severity grades by DAIDS, for levels of calcium (low=hypocalcemia; high=hypercalcemia), glu. (low=hypoglycemia; high=hyperglycemia), pot. (low=hypokalemia; high=hyperkalemia), and sod. (low=hyponatremia; high=hypernatremia). Per the DAIDS toxicity table, the grade ranges for each parameter are as follows: Grade (G) 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
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Hide Analysis Population Description
Safety DB Population: all randomized participants who had received study drug in the DB Phase
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 449
Measure Type: Number
Unit of Measure: participants
Calcium (hypocalcemia), Any Grade Increase 173 343
Calcium (hypocalcemia), Increase to G1 127 211
Calcium (hypocalcemia), Increase to G2 45 126
Calcium (hypocalcemia), Increase to G3 1 4
Calcium (hypocalcemia), Increase to G4 0 2
Calcium (hypercalcemia), Any Grade Increase 1 5
Calcium (hypercalcemia), Increase to G1 0 4
Calcium (hypercalcemia), Increase to G2 1 1
Calcium (hypercalcemia), Increase to G3 0 0
Calcium (hypercalcemia), Increase to G4 0 0
Glu. (hypoglycemia), Any Grade Increase 23 58
Glu. (hypoglycemia), Increase to G1 14 30
Glu. (hypoglycemia), Increase to G2 6 22
Glu. (hypoglycemia), Increase to G3 1 4
Glu. (hypoglycemia), Increase to G4 2 2
Glu. (hyperglycemia), Any Grade Increase 111 239
Glu. (hyperglycemia), Increase to G1 28 61
Glu. (hyperglycemia), Increase to G2 62 148
Glu. (hyperglycemia), Increase to G3 19 29
Glu. (hyperglycemia), Increase to G4 2 1
Pot. (hyperkalemia), Any Grade Increase 6 10
Pot. (hyperkalemia), Increase to G1 2 6
Pot. (hyperkalemia), Increase to G2 1 2
Pot. (hyperkalemia), Increase to G3 1 1
Pot. (hyperkalemia), Increase to G4 2 1
Pot. (hypokalemia), Any Grade Increase 33 58
Pot. (hypokalemia), Increase to G1 29 53
Pot. (hypokalemia), Increase to G2 4 5
Pot. (hypokalemia), Increase to G3 0 0
Pot. (hypokalemia), Increase to G4 0 0
Sod. (hypernatremia), Any Grade Increase 9 12
Sod. (hypernatremia), Increase to G1 9 11
Sod. (hypernatremia), Increase to G2 0 0
Sod. (hypernatremia), Increase to G3 0 0
Sod. (hypernatremia), Increase to G4 0 1
Sod. (hyponatremia), Any Grade Increase 65 151
Sod. (hyponatremia), Increase to G1 62 134
Sod. (hyponatremia), Increase to G2 3 11
Sod. (hyponatremia), Increase to G3 0 3
Sod. (hyponatremia), Increase to G4 0 3
16.Secondary Outcome
Title Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters (Hemoglobin, Lymphocytes [Lym.], Total Neutrophils [Tot Neu.], and White Blood Cells [WBC]), Per DAIDS During the DB Phase
Hide Description Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL during the DB Phase are reported, per severity grades by DAIDS, for levels of hemoglobin (low=anemia), lymphocytes (low=lymphocytopenia), total neutrophils (low=neutropenia), and white blood cells (low=leukocytopenia). Per the DAIDS toxicity table, grade ranges for each parameter are as follows: Grade (G) 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
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Hide Analysis Population Description
Safety DB Population
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 449
Measure Type: Number
Unit of Measure: participants
Hemoglobin (anemia), Any Grade Increase 148 324
Hemoglobin (anemia), Increase to G1 45 91
Hemoglobin (anemia), Increase to G2 63 128
Hemoglobin (anemia), Increase to G3 37 98
Hemoglobin (anemia), Increase to G4 3 7
Lym. (lymphocytopenia), Any Grade Increase 123 300
Lym. (lymphocytopenia), Increase to G1 16 26
Lym. (lymphocytopenia), Increase to G2 28 50
Lym. (lymphocytopenia), Increase to G3 43 96
Lym. (lymphocytopenia), Increase to G4 36 128
Tot Neu. (neutropenia), Any Grade Increase 196 394
Tot Neu. (neutropenia), Increase to G1 32 90
Tot Neu. (neutropenia), Increase to G2 39 104
Tot Neu. (neutropenia), Increase to G3 80 129
Tot Neu. (neutropenia), Increase to G4 45 71
WBC (leukocytopenia), Any Grade Increase 187 376
WBC (leukocytopenia), Increase to G1 51 94
WBC (leukocytopenia), Increase to G2 59 142
WBC (leukocytopenia), Increase to G3 68 117
WBC (leukocytopenia), Increase to G4 9 23
17.Secondary Outcome
Title Number of Participants in the Indicated Categories for Cataract Event During the DB Phase, Per Clinical Events Committee (CEC) Adjudication During the DB Phase
Hide Description Ophthalmic (pertaining to eye) assessments were performed during the study. A cataract event is defined as an event ascertained to be a cataract (opacity or cloudiness of the lens of the eye, causing impairment of vision) by at least one of the CEC members (comprised of expert ophthalmologists who provided objective medical review of the blinded ophthalmic data). Per the CEC, cataract events were categorized as: (1) Cataract Progression (CP; progression of cataracts present at BL); and (2) Incident Cataract (IC; development of new cataracts). One eye=unilateral; both eyes=bilateral.
Time Frame From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
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Hide Analysis Population Description
Safety DB Population
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 232 449
Measure Type: Number
Unit of Measure: participants
Unilateral CP, Genotype 2/3 1 2
Unilateral CP, Non-genotype 2/3 2 3
Unilateral CP, Missing genotype 0 1
Bilateral CP, Genotype 2/3 1 6
Bilateral CP, Non-genotype 2/3 0 9
Unilateral IP, Genotype 2/3 0 1
Unilateral IP, Non-genotype 2/3 2 6
Bilateral IP, Genotype 2/3 2 2
Bilateral IP, Non-genotype 2/3 0 8
18.Secondary Outcome
Title Number of Participants Assessed as Normal and Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at the Indicated Time Points During the DB Phase
Hide Description Duplicate 12-lead ECGs were required at Screening/BL, Antiviral BL, and at 12 weekly intervals during the study. The investigator assigned an ECG status of normal, abnormal, CS, or NCS; a status of "abnormal" alone indicates that the investigator did not determine if ECG was CS or NCS. Normal, all ECG parameters within accepted normal ranges. Abnormal, ECG finding(s) outside of normal ranges. CS, ECG with a CS abnormality that meets exclusion criteria. NCS, ECG with an abnormality not CS or meeting exclusion criteria, per Investigator, based on reasonable standards of clinical judgment.
Time Frame DB Phase: Antiviral BL (up to Week 10); End of Treatment (up to Week 52); and 24-week FU (up to Week 72)
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Hide Analysis Population Description
Safety DB Population. Only those participants contributing data at the indicated time points were analyzed. Worst ECG post-BL is the worst ECG assessment reported for a participant at a post-BL assessment and could be Normal, Abnormal - NCS, Abnormal - CS, or Abnormal (NCS or CS not given).
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 229 447
Measure Type: Number
Unit of Measure: participants
Antiviral BL, Normal, n=219, 423 149 278
Antiviral BL, Abnormal - NCS, n=219, 423 53 108
Antiviral BL, Abnormal - CS, n=219, 423 17 37
End of Treatment, Normal, n=198, 384 139 251
End of Treatment, Abnormal - NCS, n=198, 384 50 108
End of Treatment, Abnormal - CS, n=198, 384 9 24
End of Treatment, Abnormal, n=198, 384 0 1
24-week FU, Normal, n=186, 368 120 235
24-week FU, Abnormal - NCS, n=186, 368 53 106
24-week FU, Abnormal - CS, n=186, 368 13 27
Worst ECG post-BL, Normal, n=229, 447 105 188
Worst ECG post-BL, Abnormal - NCS, n=229, 447 87 186
Worst ECG post-BL, Abnormal - CS, n=229, 447 37 72
Worst ECG post-BL, Abnormal, n=229, 447 0 1
19.Secondary Outcome
Title Number of Participants With CS and NCS Change From Baseline for 12-lead ECG at the Indicated Time Points During the DB Phase
Hide Description Duplicate 12-lead ECGs were required at Screening/BL, Antiviral BL, and at 12 weekly intervals during the study. The number of participants with a CS or a NCS change from baseline in ECG status was reported, as determined by the Investigator based on a reasonable standard of clinical judgment. "Not applicable" indicates that information was not provided by the investigator on whether the change from baseline ECG was CS or NCS.
Time Frame End of Treatment (up to Week 52); and 24-week FU (up to Week 72)
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Hide Analysis Population Description
Safety DB Population. Only those participants contributing data at the indicated time points were analyzed.
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 198 383
Measure Type: Number
Unit of Measure: participants
End of Treatment, CS change from BL, n=198, 383 2 5
End of Treatment, NCS change from BL, n=198, 383 196 377
End of Treatment, Not applicable, n=198, 383 0 1
24-week FU, CS change from BL, n=186, 369 1 8
24-week FU, NCS change from BL, n=186, 369 185 361
20.Secondary Outcome
Title Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During the DB Phase
Hide Description Participant's blood pressure was measured at the indicated time points during the study. Systolic blood pressure is a measure of blood pressure while the heart is beating. Diastolic blood pressure is a measure of blood pressure while the heart is relaxed. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.
Time Frame DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety DB Population. Only those participants contributing data at the indicated time points were analyzed.
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 231 444
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury (mmHg)
SBP, Week 1, n=231, 443 -3.3  (13.66) -2.7  (13.48)
SBP, Week 2, n=227, 437 -5.0  (13.75) -3.2  (14.05)
SBP, Week 4, n=218, 429 -6.1  (13.61) -3.7  (13.63)
SBP, Week 6, n=196, 420 -4.3  (14.00) -3.9  (13.86)
SBP, Week 8, n=190, 416 -3.6  (14.04) -3.9  (14.15)
SBP, Week 12, n=165, 405 -4.0  (13.17) -3.6  (14.07)
SBP, Week 16, n=140, 376 -4.2  (13.69) -3.8  (13.88)
SBP, Week 20, n=135, 363 -4.1  (15.09) -3.2  (14.84)
SBP, Week 24, n=88, 249 -3.7  (15.88) -2.9  (15.88)
SBP, Week 28, n=74, 202 -3.0  (12.79) -3.3  (16.62)
SBP, Week 32, n=68, 183 -3.1  (11.95) -2.6  (16.12)
SBP, Week 36, n=68, 175 -2.4  (13.73) -3.0  (16.43)
SBP, Week 40, n=64, 169 -2.7  (11.95) -3.4  (16.47)
SBP, Week 44, n=64, 166 -2.5  (12.98) -3.8  (16.76)
SBP, End of Treatment, n=213, 420 -3.8  (14.94) -3.1  (15.65)
SBP, 4-week FU, n=204, 402 -0.7  (13.95) -1.2  (16.23)
SBP, 12-week FU, n=198, 401 -0.4  (14.24) -0.7  (15.68)
SBP, 24-week FU, n=197, 394 -0.1  (14.04) 0.1  (16.02)
DBP, Week 1, n=231, 443 -1.3  (9.57) -1.5  (9.21)
DBP, Week 2, n=227, 437 -2.6  (10.05) -1.8  (9.11)
DBP, Week 4, n=218, 429 -3.2  (10.01) -2.3  (10.12)
DBP, Week 6, n=196, 420 -1.9  (9.13) -3.1  (9.69)
DBP, Week 8, n=190, 416 -2.7  (9.67) -2.6  (10.03)
DBP, Week 12, n=165, 405 -3.0  (9.92) -2.8  (10.05)
DBP, Week 16, n=140, 376 -2.4  (9.19) -3.1  (10.01)
DBP, Week 20, n=135, 363 -3.5  (10.04) -2.4  (9.59)
DBP, Week 24, n=88, 249 -2.4  (10.60) -2.9  (9.95)
DBP, Week 28, n=74, 202 -3.7  (10.32) -3.0  (10.43)
DBP, Week 32, n=68, 183 -1.7  (10.93) -2.5  (9.99)
DBP, Week 36, n=68, 175 -1.5  (11.51) -3.1  (9.84)
DBP, Week 40, n=64, 169 -2.7  (10.65) -2.9  (10.99)
DBP, Week 44, n=64, 166 -2.8  (10.96) -3.2  (10.54)
DBP, End of Treatment, n=213, 420 -2.8  (10.07) -2.8  (10.26)
DBP, 4-week FU, n=204, 402 -1.8  (9.30) -1.2  (10.67)
DBP, 12-week FU, n=198, 401 -1.4  (10.48) -0.9  (10.09)
DBP, 24-week FU, n=197, 394 -0.6  (9.90) -0.3  (9.97)
21.Secondary Outcome
Title Mean Change From Baseline in Heart Rate at the Indicated Time Points During the DB Phase
Hide Description Heart rate was measured in participants at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.
Time Frame DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
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Hide Analysis Population Description
Safety DB Population. Only those participants contributing data at the indicated time points were analyzed.
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 231 443
Mean (Standard Deviation)
Unit of Measure: beats per minute
Week 1, n=231, 440 0.6  (8.99) 0.9  (8.50)
Week 2, n=227, 435 1.1  (9.31) 2.3  (9.16)
Week 4, n=217, 428 1.7  (9.83) 2.7  (9.01)
Week 6, n=195, 419 2.3  (11.74) 2.9  (8.88)
Week 8, n=190, 414 2.3  (10.27) 3.6  (9.98)
Week 12, n=164, 404 3.8  (11.30) 4.1  (9.93)
Week 16, n=140, 375 4.7  (11.81) 4.2  (9.87)
Week 20, n=135, 363 3.4  (11.05) 4.8  (9.73)
Week 24, n=88, 248 4.8  (11.34) 4.7  (10.91)
Week 28, n=73, 200 4.6  (10.29) 4.5  (9.75)
Week 32, n=68, 182 6.1  (10.48) 5.5  (10.46)
Week 36, n=68, 174 5.5  (11.55) 4.1  (11.84)
Week 40, n=64, 166 5.8  (9.33) 5.0  (10.32)
Week 44, n=64, 166 5.3  (11.30) 5.5  (9.94)
End of Treatment, n=212, 419 2.9  (10.54) 4.3  (10.84)
4-week FU, n=204, 397 2.7  (11.47) 3.5  (10.38)
12-week FU, n=197, 400 0.5  (11.23) 1.7  (10.40)
24-week FU, n=197, 393 0.1  (11.61) 0.5  (10.34)
22.Secondary Outcome
Title Mean Change From Baseline in Weight at the Indicated Time Points During the DB Phase
Hide Description The weight of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.
Time Frame DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety DB Population. Only those participants contributing data at the indicated time points were analyzed.
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 230 443
Mean (Standard Deviation)
Unit of Measure: Kilograms (kg)
Week 1, n=230, 443 -0.5  (1.83) -0.6  (1.76)
Week 2, n=227, 439 -0.7  (1.95) -0.7  (1.87)
Week 4, n=218, 430 -0.8  (2.16) -1.0  (2.39)
Week 6, n=198, 421 -1.0  (2.30) -1.2  (2.33)
Week 8, n=191, 416 -1.2  (2.63) -1.7  (2.68)
Week 12, n=165, 404 -1.4  (3.27) -2.3  (3.15)
Week 16, n=139, 377 -1.8  (3.15) -2.8  (3.19)
Week 20, n=135, 364 -2.0  (3.74) -3.3  (3.62)
Week 24, n=88, 249 -1.7  (3.59) -4.1  (3.88)
Week 28, n=74, 202 -2.5  (4.79) -4.4  (3.96)
Week 32, n=69, 184 -1.8  (3.70) -4.2  (4.01)
Week 36, n=68, 175 -1.9  (3.81) -4.4  (4.07)
Week 40, n=64, 169 -1.8  (4.10) -4.5  (4.30)
Week 44, n=65, 166 -2.0  (4.40) -4.7  (4.35)
End of Treatment, n=214, 419 -2.0  (3.88) -4.2  (4.65)
4-week FU, n=204, 404 -2.0  (3.95) -3.7  (4.68)
12-week FU, n=198, 401 -1.4  (4.51) -2.9  (5.07)
24-week FU, n=197, 393 -0.7  (5.32) -1.8  (5.14)
23.Secondary Outcome
Title Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points During the DB Phase
Hide Description The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.
Time Frame DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety DB Population. Only those participants contributing data at the indicated time points were analyzed.
Arm/Group Title Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description:
Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
Overall Number of Participants Analyzed 228 440
Mean (Standard Deviation)
Unit of Measure: Kilograms per meters squared (kg/m^2)
Week 1, n=228, 440 -0.2  (0.61) -0.2  (0.61)
Week 2, n=225, 436 -0.2  (0.67) -0.3  (0.65)
Week 4, n=216, 427 -0.3  (0.72) -0.4  (0.84)
Week 6, n=196, 418 -0.4  (0.78) -0.4  (0.80)
Week 8, n=189, 413 -0.4  (0.89) -0.6  (0.92)
Week 12, n=164, 401 -0.5  (1.11) -0.8  (1.09)
Week 16, n=138, 375 -0.7  (1.10) -1.0  (1.14)
Week 20, n=134, 362 -0.7  (1.24) -1.2  (1.27)
Week 24, n=87, 248 -0.6  (1.19) -1.5  (1.42)
Week 28, n=73, 201 -0.9  (1.63) -1.6  (1.42)
Week 32, n=68, 183 -0.7  (1.25) -1.5  (1.46)
Week 36, n=67, 174 -0.7  (1.30) -1.6  (1.51)
Week 40, n=63, 169 -0.7  (1.42) -1.6  (1.59)
Week 44, n=64, 166 -0.8  (1.53) -1.7  (1.61)
End of Treatment, n=212, 416 -0.7  (1.33) -1.5  (1.66)
4-week FU, n=202, 402 -0.7  (1.37) -1.3  (1.66)
12-week FU, n=196, 398 -0.5  (1.54) -1.0  (1.79)
24-week FU, n=195, 390 -0.3  (1.81) -0.6  (1.78)
Time Frame Adverse events (AEs) are reported for the Double-blind (DB) on-treatment + 30 days period (up to Study Week 72).
Adverse Event Reporting Description In the study, AEs were collected during the Open-Label (OL) Pre-Antiviral Treatment Phase and the Double-Blind (DB) Phase, which included antiviral therapy and a 6-month post-therapy follow-up. Data for SAEs and AEs are presented for the Safety Population, comprised of all randomized participants who received the study drug.
 
Arm/Group Title Eltrombopag: OL Phase Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Hide Arm/Group Description Participants with a platelet count of <75 giga (10^9) cells per liter (Gi/L) initially received eltrombopag 25 milligrams (mg) once daily (QD) for 2 weeks. After 2 weeks, if the platelet count was <90 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained <90 Gi/L, further dose escalations to 75 mg QD (up to 2 weeks) and 100 mg QD (up to a maximum of 3 weeks) were allowed. Participants who achieved platelet counts >=90 Gi/L during the OL Phase (maximum of up to 9 weeks) were eligible to enter the Double-blind (DB) Antiviral Treatment Phase, whereas those who failed to reach platelet counts >=90 Gi/L were discontinued from eltrombopag and had to attend the post-treatment follow-up visits. Participants completing the OL Phase were administered matching placebo tablets QD in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3). Participants completing the OL Phase continued on the same dose of eltrombopag received in the OL Phase (dose that effectively raised platelets to >=90 Gi/L) in combination with antiviral therapy (peginterferon alfa-2a and ribavirin) for a duration of either 24 or 48 weeks (for participants with Genotype 2/3) or 48 weeks (for participants with Non-Genotype 2/3).
All-Cause Mortality
Eltrombopag: OL Phase Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Eltrombopag: OL Phase Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/715 (1.12%)   35/232 (15.09%)   89/449 (19.82%) 
Blood and lymphatic system disorders       
Anemia  1  0/715 (0.00%)  1/232 (0.43%)  3/449 (0.67%) 
Neutropenia  1  0/715 (0.00%)  1/232 (0.43%)  3/449 (0.67%) 
Pancytopenia  1  0/715 (0.00%)  1/232 (0.43%)  3/449 (0.67%) 
Hemolytic Anemia  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Leukopenia  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Thrombocytopenia  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Cardiac disorders       
Acute Myocardial Infarction  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Angina Pectoris  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Pericarditis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Pleuropericarditis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Angina Unstable  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Sinus Bradycardia  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Congenital, familial and genetic disorders       
Epidermolysis Bullosa  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Ear and labyrinth disorders       
Deafness Neurosensory  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Endocrine disorders       
Goitre  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Eye disorders       
Cataract  1  0/715 (0.00%)  2/232 (0.86%)  2/449 (0.45%) 
Cataract Nuclear  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Eye Disorder  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Retinal Vein Occlusion  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Visual Acuity Reduced  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Gastrointestinal disorders       
Gastric Hemorrhage  1  1/715 (0.14%)  0/232 (0.00%)  0/449 (0.00%) 
Hemorrhoids  1  1/715 (0.14%)  1/232 (0.43%)  0/449 (0.00%) 
Large Intestine Perforation  1  1/715 (0.14%)  0/232 (0.00%)  1/449 (0.22%) 
Oesophageal Varices Hemorrhage  1  1/715 (0.14%)  2/232 (0.86%)  7/449 (1.56%) 
Ascites  1  0/715 (0.00%)  3/232 (1.29%)  4/449 (0.89%) 
Upper Gastrointestinal Hemorrhage  1  0/715 (0.00%)  0/232 (0.00%)  4/449 (0.89%) 
Colitis  1  0/715 (0.00%)  0/232 (0.00%)  2/449 (0.45%) 
Diarrhea  1  0/715 (0.00%)  0/232 (0.00%)  2/449 (0.45%) 
Gastric Varices Hemorrhage  1  0/715 (0.00%)  0/232 (0.00%)  2/449 (0.45%) 
Gastrointestinal Hemorrhage  1  0/715 (0.00%)  0/232 (0.00%)  2/449 (0.45%) 
Abdominal Discomfort  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Abdominal Pain  1  0/715 (0.00%)  2/232 (0.86%)  1/449 (0.22%) 
Abdominal Pain Upper  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Abdominal Strangulated Hernia  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Gastritis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Hematemesis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Intestinal Obstruction  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Nausea  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Oesophageal Hemorrhage  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Pancreatitis  1  0/715 (0.00%)  1/232 (0.43%)  1/449 (0.22%) 
Pancreatitis Acute  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Peptic Ulcer  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Periodontitis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Peritonitis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Vomiting  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Abdominal Distension  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Enteritis  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Varices Oesophageal  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
General disorders       
Pyrexia  1  1/715 (0.14%)  0/232 (0.00%)  3/449 (0.67%) 
Chest Pain  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Death  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
General Physical Health Deterioration  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Edema Peripheral  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Multi-organ Failure  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Hepatobiliary disorders       
Hepatic Failure  1  0/715 (0.00%)  1/232 (0.43%)  7/449 (1.56%) 
Cholecystitis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Cholecystitis Acute  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Hepatic Function Abnormal  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Hepatitis Alcoholic  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Hepatorenal Syndrome  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Cholelithiasis  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Hepatic Cirrhosis  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Portal Vein Thrombosis  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Infections and infestations       
Pneumonia  1  1/715 (0.14%)  2/232 (0.86%)  4/449 (0.89%) 
Gastroenteritis  1  0/715 (0.00%)  1/232 (0.43%)  4/449 (0.89%) 
Peritonitis Bacterial  1  0/715 (0.00%)  2/232 (0.86%)  3/449 (0.67%) 
Urinary Tract Infection  1  0/715 (0.00%)  0/232 (0.00%)  3/449 (0.67%) 
Abscess Limb  1  0/715 (0.00%)  1/232 (0.43%)  2/449 (0.45%) 
Cellulitis  1  0/715 (0.00%)  1/232 (0.43%)  2/449 (0.45%) 
Septic Shock  1  0/715 (0.00%)  0/232 (0.00%)  2/449 (0.45%) 
Bacteremia  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Bacterial Infection  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Bronchitis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Diarrhea Infectious  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Disseminated Tuberculosis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Erysipelas  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Meningitis Cryptococcal  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Prostatic Abscess  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Renal Abscess  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Sepsis  1  0/715 (0.00%)  1/232 (0.43%)  1/449 (0.22%) 
Subcutaneous Abscess  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Urosepsis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Acinetobacter Bacteremia  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Appendicitis Perforated  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Dacryocystitis  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Pyelonephritis  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Pyelonephritis Acute  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Sinusitis  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Staphylococcal Infection  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Injury, poisoning and procedural complications       
Forearm Fracture  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Limb Traumatic Amputation  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Traumatic Lung Injury  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Retinal Injury  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Investigations       
Blood Creatinine Increased  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Transaminases Increased  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Metabolism and nutrition disorders       
Hyperglycemia  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Musculoskeletal and connective tissue disorders       
Bursitis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Fasciitis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Juvenile Arthritis  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Hepatic Neoplasm Malignant  1  2/715 (0.28%)  2/232 (0.86%)  6/449 (1.34%) 
Lung Neoplasm Malignant  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Nervous system disorders       
Hepatic Encephalopathy  1  0/715 (0.00%)  0/232 (0.00%)  4/449 (0.89%) 
Encephalopathy  1  0/715 (0.00%)  0/232 (0.00%)  2/449 (0.45%) 
Brain Edema  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Coma  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Convulsion  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Vocal Cord Paralysis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Ruptured Cerebral Aneurysm  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Psychiatric disorders       
Mental Status Changes  1  0/715 (0.00%)  0/232 (0.00%)  2/449 (0.45%) 
Renal and urinary disorders       
Renal Failure  1  0/715 (0.00%)  1/232 (0.43%)  2/449 (0.45%) 
Renal Failure Acute  1  0/715 (0.00%)  0/232 (0.00%)  2/449 (0.45%) 
Cystitis Ulcerative  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Urethral Polyp  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Reproductive system and breast disorders       
Dyspnea Exertional  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Prostatitis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Respiratory, thoracic and mediastinal disorders       
Pleural Effusion  1  0/715 (0.00%)  0/232 (0.00%)  2/449 (0.45%) 
Dyspnea  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Epistaxis  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Respiratory Failure  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Pleurisy  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Social circumstances       
Alcohol Use  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Surgical and medical procedures       
Portal Shunt  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Vascular disorders       
Hypertensive Crisis  1  1/715 (0.14%)  0/232 (0.00%)  0/449 (0.00%) 
Bleeding Varicose Vein  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Venous Thrombosis Limb  1  0/715 (0.00%)  0/232 (0.00%)  1/449 (0.22%) 
Varicose Vein  1  0/715 (0.00%)  1/232 (0.43%)  0/449 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Eltrombopag: OL Phase Placebo+Antiviral Therapy: DB Phase Eltrombopag+Antiviral Therapy: DB Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   49/715 (6.85%)   219/232 (94.40%)   424/449 (94.43%) 
Blood and lymphatic system disorders       
Neutropenia  1  0/715 (0.00%)  95/232 (40.95%)  170/449 (37.86%) 
Anemia  1  0/715 (0.00%)  78/232 (33.62%)  183/449 (40.76%) 
Thrombocytopenia  1  0/715 (0.00%)  85/232 (36.64%)  69/449 (15.37%) 
Leukopenia  1  0/715 (0.00%)  39/232 (16.81%)  70/449 (15.59%) 
Gastrointestinal disorders       
Nausea  1  0/715 (0.00%)  30/232 (12.93%)  86/449 (19.15%) 
Diarrhea  1  0/715 (0.00%)  27/232 (11.64%)  82/449 (18.26%) 
Vomiting  1  0/715 (0.00%)  17/232 (7.33%)  31/449 (6.90%) 
Abdominal Pain  1  0/715 (0.00%)  12/232 (5.17%)  33/449 (7.35%) 
Dyspepsia  1  0/715 (0.00%)  16/232 (6.90%)  27/449 (6.01%) 
Abdominal Pain Upper  1  0/715 (0.00%)  11/232 (4.74%)  29/449 (6.46%) 
Ascites  1  0/715 (0.00%)  7/232 (3.02%)  32/449 (7.13%) 
Constipation  1  0/715 (0.00%)  11/232 (4.74%)  28/449 (6.24%) 
General disorders       
Fatigue  1  0/715 (0.00%)  60/232 (25.86%)  139/449 (30.96%) 
Pyrexia  1  0/715 (0.00%)  53/232 (22.84%)  139/449 (30.96%) 
Influenza Like Illness  1  0/715 (0.00%)  40/232 (17.24%)  70/449 (15.59%) 
Asthenia  1  0/715 (0.00%)  34/232 (14.66%)  66/449 (14.70%) 
Edema Peripheral  1  0/715 (0.00%)  20/232 (8.62%)  56/449 (12.47%) 
Chills  1  0/715 (0.00%)  12/232 (5.17%)  58/449 (12.92%) 
Irritability  1  0/715 (0.00%)  17/232 (7.33%)  46/449 (10.24%) 
Hepatobiliary disorders       
Hyperbilirubinemia  1  0/715 (0.00%)  5/232 (2.16%)  38/449 (8.46%) 
Infections and infestations       
Urinary Tract Infection  1  0/715 (0.00%)  8/232 (3.45%)  39/449 (8.69%) 
Upper Respiratory Tract Infection  1  0/715 (0.00%)  12/232 (5.17%)  24/449 (5.35%) 
Investigations       
Blood Bilirubin Increased  1  0/715 (0.00%)  8/232 (3.45%)  44/449 (9.80%) 
White Blood Cell Count Decreased  1  0/715 (0.00%)  9/232 (3.88%)  32/449 (7.13%) 
Hemoglobin Decreased  1  0/715 (0.00%)  9/232 (3.88%)  31/449 (6.90%) 
Weight Decreased  1  0/715 (0.00%)  9/232 (3.88%)  25/449 (5.57%) 
Metabolism and nutrition disorders       
Decreased Appetite  1  0/715 (0.00%)  30/232 (12.93%)  78/449 (17.37%) 
Musculoskeletal and connective tissue disorders       
Myalgia  1  0/715 (0.00%)  26/232 (11.21%)  65/449 (14.48%) 
Arthralgia  1  0/715 (0.00%)  17/232 (7.33%)  55/449 (12.25%) 
Muscle Spasms  1  0/715 (0.00%)  15/232 (6.47%)  46/449 (10.24%) 
Back Pain  1  0/715 (0.00%)  10/232 (4.31%)  26/449 (5.79%) 
Nervous system disorders       
Headache  1  49/715 (6.85%)  47/232 (20.26%)  107/449 (23.83%) 
Dizziness  1  0/715 (0.00%)  24/232 (10.34%)  26/449 (5.79%) 
Psychiatric disorders       
Insomnia  1  0/715 (0.00%)  44/232 (18.97%)  79/449 (17.59%) 
Depression  1  0/715 (0.00%)  11/232 (4.74%)  38/449 (8.46%) 
Anxiety  1  0/715 (0.00%)  13/232 (5.60%)  18/449 (4.01%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/715 (0.00%)  34/232 (14.66%)  77/449 (17.15%) 
Epistaxis  1  0/715 (0.00%)  33/232 (14.22%)  30/449 (6.68%) 
Dyspnea  1  0/715 (0.00%)  15/232 (6.47%)  38/449 (8.46%) 
Dyspnea Exertional  1  0/715 (0.00%)  16/232 (6.90%)  28/449 (6.24%) 
Oropharyngeal Pain  1  0/715 (0.00%)  9/232 (3.88%)  30/449 (6.68%) 
Skin and subcutaneous tissue disorders       
Pruritus  1  0/715 (0.00%)  27/232 (11.64%)  68/449 (15.14%) 
Rash  1  0/715 (0.00%)  24/232 (10.34%)  49/449 (10.91%) 
Alopecia  1  0/715 (0.00%)  15/232 (6.47%)  50/449 (11.14%) 
Dry Skin  1  0/715 (0.00%)  14/232 (6.03%)  31/449 (6.90%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00516321    
Other Study ID Numbers: TPL103922
First Submitted: August 13, 2007
First Posted: August 15, 2007
Results First Submitted: March 22, 2012
Results First Posted: July 30, 2012
Last Update Posted: November 5, 2013