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

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ClinicalTrials.gov Identifier: NCT00529568
Recruitment Status : Completed
First Posted : September 14, 2007
Results First Posted : May 17, 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: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hepatitis C, Chronic
Interventions Drug: eltrombopag
Drug: placebo
Enrollment 759
Recruitment Details  
Pre-assignment Details The number of enrolled participants in the protocol record (n=759) reflects the number of participants randomized to double-blind treatment after completing the Open-label Phase.
Arm/Group Title Eltrombopag: Open-label 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 <100 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained <100 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 >=100 Gi/L during the Open-label 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 >=100 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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 Pre-Antiviral Treatment Phase
Started 805 0 0
Completed 759 0 0
Not Completed 46 0 0
Reason Not Completed
Adverse Event             5             0             0
Lost to Follow-up             12             0             0
Protocol Violation             5             0             0
Physician Decision             8             0             0
Insufficient Platelet Response             13             0             0
Withdrawal by Subject             3             0             0
Period Title: Double-bilnd Antiviral Treatment Phase
Started 0 253 506
Completed 0 205 404
Not Completed 0 48 102
Reason Not Completed
Adverse Event             0             10             27
Protocol Violation             0             1             0
Lost to Follow-up             0             15             48
Physician Decision             0             5             8
Withdrawal by Subject             0             17             19
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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 253 506 759
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 253 participants 506 participants 759 participants
52.0  (9.15) 52.4  (8.61) 52.3  (8.79)
[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 253 participants 506 participants 759 participants
Female
93
  36.8%
185
  36.6%
278
  36.6%
Male
160
  63.2%
321
  63.4%
481
  63.4%
[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 253 participants 506 participants 759 participants
African American (A)/African 4 8 12
American Indian or Alaska Native 0 1 1
White (W) 188 388 576
Central/South Asian 16 43 59
Japanese/East Asian /South East Asian 45 64 109
American Indian or Alaska Native and White 0 1 1
African A/African and A Indian/Alaska Native and W 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 253 participants 506 participants 759 participants
Genotype 1 160 320 480
Genotype 2 28 40 68
Genotype 3 47 113 160
Genotype 4 17 30 47
Genotype 5 0 0 0
Genotype 6 0 1 1
Genotype 7 0 0 0
Missing 1 2 3
[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 253 participants 506 participants 759 participants
Class A 242 487 729
Class B 11 17 28
Class C 0 0 0
Missing 0 2 2
[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), and >=10 = Class C (severe).
Number of participants with or without previous interferon (IFN) use   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 253 participants 506 participants 759 participants
Naïve 182 347 529
Experienced 71 159 230
[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 253 participants 506 participants 759 participants
Score: F0/F1/F2 19 46 65
Score: F3/F4 199 405 604
Missing 35 55 90
[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 253 participants 506 participants 759 participants
Normal 49 113 162
Elevated 204 393 597
[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 253 participants 506 participants 759 participants
1656788.0  (2564763.45) 1702729.6  (3066411.11) 1687415.8  (2907191.97)
[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 three participants 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 253 participants 506 participants 759 participants
56.56  (13.571) 56.85  (13.311) 56.75  (13.390)
[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 are defined as those with non-detectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) at the end of treatment and all subsequent planned visits up to 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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 253 506
Measure Type: Number
Unit of Measure: participants
32 97
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 0.0202
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 6.0
Confidence Interval (2-Sided) 95%
1.2 to 10.9
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 (>=) 100 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 >=100 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 <100 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained <100 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 >=100 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 >=100 Gi/L were discontinued from eltrombopag and had to attend the post-treatment follow-up visits.
Overall Number of Participants Analyzed 805
Measure Type: Number
Unit of Measure: participants
773
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 <100 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 <100 Gi/L. Participants who achieved platelet counts >=100 Gi/L when receiving 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 >=100 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 <100 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained <100 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 >=100 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 >=100 Gi/L were discontinued from eltrombopag and had to attend the post-treatment follow-up visits.
Overall Number of Participants Analyzed 759
Measure Type: Number
Unit of Measure: participants
25 mg 443
50 mg 208
75 mg 77
100 mg 31
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 <100 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained <100 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 >=100 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 >=100 Gi/L were discontinued from eltrombopag and had to attend the post-treatment follow-up visits.
Overall Number of Participants Analyzed 797
Median (Full Range)
Unit of Measure: Gi/L
Baseline, n=797
59.0
(12 to 95)
Day 1, n=714
58.0
(5 to 117)
Week 1, n=791
77.0
(5 to 223)
Week 2, n=530
93.0
(9 to 489)
Week 3, n=288
89.0
(10 to 504)
Week 4, n=161
90.0
(10 to 280)
Week 5, n=98
92.0
(9 to 252)
Week 6, n=55
86.0
(14 to 138)
Week 7, n=35
78.0
(11 to 136)
Week 8, n=24
87.5
(15 to 146)
Week 9, n=4
85.5
(66 to 107)
Antiviral Baseline, n=48
131.5
(76 to 274)
End of Treatment/Withdrawal, n=22
76.5
(13 to 257)
Last on Treatment, n=39
87.0
(13 to 267)
Week 4 Follow-Up, n=20
42.0
(11 to 156)
Week 12 Follow-Up, n=15
43.0
(8 to 91)
Week 24 Follow-Up, n=14
41.0
(13 to 87)
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. 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 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.
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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 252 505
Median (Full Range)
Unit of Measure: Gi/L
Baseline, n=238, 460
140.0
(63 to 365)
136.0
(43 to 400)
Week 1, n=247, 494
120.0
(42 to 366)
116.0
(46 to 466)
Week 2, n=244, 492
89.5
(27 to 318)
124.0
(38 to 553)
Week 4, n=228, 487
51.0
(20 to 180)
105
(19 to 389)
Week 6, n=206, 473
49.5
(20 to 200)
100.0
(22 to 417)
Week 8, n=192, 473
50.0
(10 to 191)
100.0
(19 to 486)
Week 12, n=176, 451
49.7
(21 to 264)
104.0
(10 to 444)
Week 16, n=145, 405
48.0
(20 to 262)
102.0
(13 to 365)
Week 20, n=134, 378
50.0
(23 to 257)
103.0
(21 to 373)
Week 24, n=99, 263
49.0
(19 to 200)
102.0
(18 to 448)
Week 28, n=74, 212
52.5
(22 to 193)
102.0
(20 to 355)
Week 32, n=67, 199
49.0
(22 to 195)
107.0
(14 to 295)
Week 36, n=63, 185
50.0
(16 to 198)
106.0
(29 to 268)
Week 40, n=58, 174
53.7
(19 to 195)
106.5
(10 to 351)
Week 44, n=59, 168
53.0
(26 to 197)
108.7
(26 to 330)
End of Treatment/Withdrawal, n=240, 468
51.0
(10 to 275)
106.5
(10 to 445)
Last on Treatment, n=253, 505
50.0
(17 to 300)
105.0
(10 to 330)
4 week follow up, n=221, 424
63.0
(4 to 225)
89.0
(12 to 333)
12 week follow up, n=209, 430
57.0
(15 to 285)
62.0
(8 to 280)
24 week follow up, n=201, 395
57.0
(8 to 231)
59.0
(4 to 297)
6.Secondary Outcome
Title Number of Participants in the Indicated Categories for Minimum Platelet Count With Antiviral Therapy
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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 253 506
Measure Type: Number
Unit of Measure: participants
<25 Gi/L 34 20
>=25 to <50 Gi/L 159 76
>=50 to <90 Gi/L 49 263
>=90 to <150 Gi/L 10 135
>=150 to <200 Gi/L 0 8
>=200 to <400 Gi/L 0 4
>=400 Gi/L 0 0
Missing 1 0
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 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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 253 506
Measure Type: Number
Unit of Measure: participants
RVR 34 78
eRVR 27 69
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 drop or undetectable) after 12 weeks of antiviral treatment. cEVR is defined as undetectable HCV RNA after 12 weeks of antiviral treatment.
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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 253 506
Measure Type: Number
Unit of Measure: participants
EVR 103 313
cEVR 57 174
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 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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 253 506
Measure Type: Number
Unit of Measure: participants
ETR 59 190
SVR12 29 106
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). When possible, every effort was made to maintain the recommended dose of antiviral therapy for the treatment duration in the DB Phase. However, when 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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 253 506
Measure Type: Number
Unit of Measure: participants
0 68 231
1 76 101
2 40 75
3 34 47
>3 35 52
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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 171 208
Mean (Standard Deviation)
Unit of Measure: weeks
Peginterferon alfa-2a dose reduction, n=171, 208 6.58  (7.336) 10.64  (9.305)
Ribavirin dose reduction, n=79, 189 12.43  (9.681) 10.99  (8.984)
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 (µg). For peginterferon dose modification, downward adjustments in one-level increments were considered. The lowest dose of peginterferon alfa-2a that was allowed to be administered was 45 µg. When dose adjustment was required for moderate to severe adverse reactions (clinical and/or laboratory), an initial dose reduction to 135 µg was generally adequate. In some cases, a dose reduction to 90 µg or 45 µg 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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 253 506
Measure Type: Number
Unit of Measure: participants
<=25% 44 89
>25% to <=34% 33 35
>34% to <=50% 115 112
>50% 33 30
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 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)
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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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 253 506
Measure Type: Number
Unit of Measure: participants
164 242
14.Secondary Outcome
Title Number of Participants 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)
Hide Description There are two genetic variants (rs12979860 and rs8099917) mapping near IL28B associated with both interferon-induced SVR and spontaneous HCV clearance. IL28B genotype distribution by response to antiviral therapy (SVR/RVR responders: those who achieved SVR/RVR; SVR/RVR non-responders: those who did not achieve SVR/RVR) 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. Only those participants who were analyzed for SVR and RVR were considered.
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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 105 205
Measure Type: Number
Unit of Measure: participants
SVR, rs12979860 (CC), R; n=12, 50 10 28
SVR, rs12979860 (CC), NR; n=105, 205 24 58
SVR, rs12979860 (CT), R; n=12, 50 2 18
SVR, rs12979860 (CT), NR; n=105, 205 60 111
SVR, rs12979860 (TT), R; n=12, 50 0 4
SVR, rs12979860 (TT), NR; n=105, 205 21 36
SVR, rs8099917 (TT), R; n=12, 50 11 36
SVR, rs8099917 (TT), NR; n=105, 205 48 89
SVR, rs8099917 (GT), R; n=12, 50 1 13
SVR, rs8099917 (GT), NR; n=105, 205 51 99
SVR, rs8099917 (GG), R; n=12, 50 0 1
SVR, rs8099917 (GG), NR; n=105, 205 6 17
RVR, rs12979860 (CC), R; n=11, 33 6 21
RVR, rs12979860 (CC), NR; n=106, 222 28 65
RVR, rs12979860 (CT), R; n=11, 33 5 11
RVR, rs12979860 (CT), NR; n=106, 222 57 118
RVR, rs12979860 (TT), R; n=11, 33 0 1
RVR, rs12979860 (TT), NR; n=106, 222 21 39
RVR, rs8099917 (TT), R, n=11, 33 9 28
RVR, rs8099917 (TT), NR; n=106, 222 50 97
RVR, rs8099917 (GT), R; n=11, 33 2 5
RVR, rs8099917 (GT), NR; n=106, 222 50 107
RVR, rs8099917 (GG), R; n=11, 33 0 0
RVR, rs8099917 (GG), R; n=106, 222 6 18
15.Secondary Outcome
Title Number of Participants 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)
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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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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 252 506
Measure Type: Number
Unit of Measure: participants
Calcium (hypocalcemia), Any Grade Increase 184 374
Calcium (hypocalcemia), Increase to G1 140 246
Calcium (hypocalcemia), Increase to G2 42 122
Calcium (hypocalcemia), Increase to G3 2 4
Calcium (hypocalcemia), Increase to G4 0 2
Calcium (hypercalcemia), Any Grade Increase 2 1
Calcium (hypercalcemia), Increase to G1 1 1
Calcium (hypercalcemia), Increase to G2 1 0
Calcium (hypercalcemia), Increase to G3 0 0
Calcium (hypercalcemia), Increase to G4 0 0
Glu. (hypoglycemia), Any Grade Increase 31 90
Glu. (hypoglycemia), Increase to G1 17 45
Glu. (hypoglycemia), Increase to G2 10 31
Glu. (hypoglycemia), Increase to G3 4 9
Glu. (hypoglycemia), Increase to G4 0 5
Glu. (hyperglycemia), Any Grade Increase 128 277
Glu. (hyperglycemia), Increase to G1 31 68
Glu. (hyperglycemia), Increase to G2 77 161
Glu. (hyperglycemia), Increase to G3 19 44
Glu. (hyperglycemia), Increase to G4 1 4
Pot. (hyperkalemia), Any Grade Increase 3 15
Pot. (hyperkalemia), Increase to G1 2 7
Pot. (hyperkalemia), Increase to G2 1 3
Pot. (hyperkalemia), Increase to G3 0 2
Pot. (hyperkalemia), Increase to G4 0 3
Pot. (hypokalemia), Any Grade Increase 53 74
Pot. (hypokalemia), Increase to G1 48 66
Pot. (hypokalemia), Increase to G2 5 6
Pot. (hypokalemia), Increase to G3 0 2
Pot. (hypokalemia), Increase to G4 0 0
Sod. (hypernatremia), Any Grade Increase 14 21
Sod. (hypernatremia), Increase to G1 14 20
Sod. (hypernatremia), Increase to G2 0 1
Sod. (hypernatremia), Increase to G3 0 0
Sod. (hypernatremia), Increase to G4 0 0
Sod. (hyponatremia), Any Grade Increase 72 128
Sod. (hyponatremia), Increase to G1 69 118
Sod. (hyponatremia), Increase to G2 3 8
Sod. (hyponatremia), Increase to G3 0 1
Sod. (hyponatremia), Increase to G4 0 1
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
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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 252 506
Measure Type: Number
Unit of Measure: participants
Hemoglobin (anemia), Any Grade Increase 161 361
Hemoglobin (anemia), Increase to G1 46 112
Hemoglobin (anemia), Increase to G2 64 129
Hemoglobin (anemia), Increase to G3 48 114
Hemoglobin (anemia), Increase to G4 3 6
Lym. (lymphocytopenia), Any Grade Increase 136 346
Lym. (lymphocytopenia), Increase to G1 16 43
Lym. (lymphocytopenia), Increase to G2 38 80
Lym. (lymphocytopenia), Increase to G3 48 109
Lym. (lymphocytopenia), Increase to G4 34 114
Tot Neu. (neutropenia), Any Grade Increase 208 394
Tot Neu. (neutropenia), Increase to G1 50 106
Tot Neu. (neutropenia), Increase to G2 53 113
Tot Neu. (neutropenia), Increase to G3 73 128
Tot Neu. (neutropenia), Increase to G4 32 47
WBC (leukocytopenia), Any Grade Increase 191 391
WBC (leukocytopenia), Increase to G1 56 113
WBC (leukocytopenia), Increase to G2 69 145
WBC (leukocytopenia), Increase to G3 58 110
WBC (leukocytopenia), Increase to G4 8 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
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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 252 506
Measure Type: Number
Unit of Measure: participants
Unilateral CP, Genotype 2/3 0 1
Unilateral CP, Non-genotype 2/3 4 6
Bilateral CP, Genotype 2/3 3 1
Bilateral CP, Non-genotype 2/3 1 7
Unilateral IP, Genotype 2/3 1 4
Unilateral IP, Non-genotype 2/3 1 6
Bilateral IP, Genotype 2/3 3 1
Bilateral IP, Non-genotype 2/3 3 10
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 number of participants with an ECG status of normal, abnormal, CS, or NCS, as determined by the Investigator, was reported. 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.
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-2b 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 &gt;=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 252 505
Measure Type: Number
Unit of Measure: participants
Antiviral BL, Normal, n=232, 478 147 332
Antiviral BL, Abnormal - NCS, n=232, 478 63 103
Antiviral BL, Abnormal - CS, n=232, 478 22 43
End of Treatment, Normal, n=218, 428 134 291
End of Treatment, Abnormal - NCS, n=218, 428 62 103
End of Treatment, Abnormal - CS, n=218, 428 22 34
24-week FU, Normal, n=194, 383 123 238
24-week FU, Abnormal - NCS, n=194, 383 49 107
24-week FU, Abnormal - CS, n=194, 383 22 38
Worst ECG post-BL, Normal, n=252, 505 113 233
Worst ECG post-BL, Abnormal - NCS, n=252, 505 91 171
Worst ECG post-BL, Abnormal - CS, n=252, 505 48 101
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 and a NCS change from baseline in ECG status, as determined by the Investigator, was reported. 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. "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-2b 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 &gt;=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 218 428
Measure Type: Number
Unit of Measure: participants
End of Treatment, CS change from BL, n=218, 428 0 7
End of Treatment, NCS change from BL, n=218, 428 218 420
End of Treatment, Not applicable, n=218, 428 0 1
24-week FU, CS change from BL, n=194, 383 1 4
24-week FU, NCS change from BL, n=194, 383 193 379
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)
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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-2b 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 &gt;=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 246 494
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury (mmHg)
SBP, Week 1, n=246, 491 -3.00  (13.541) -2.36  (12.296)
SBP, Week 2, n=242, 494 -3.25  (13.800) -3.74  (13.122)
SBP, Week 4, n=228, 485 -3.75  (13.781) -3.91  (13.780)
SBP, Week 6, n=206, 471 -3.36  (14.405) -3.85  (14.624)
SBP, Week 8, n=190, 472 -2.72  (14.073) -4.33  (14.401)
SBP, Week 12, n=175, 452 -2.16  (15.297) -4.30  (14.377)
SBP, Week 16, n=143, 403 -3.16  (15.426) -4.59  (13.579)
SBP, Week 20, n=133, 374 -2.50  (14.387) -4.12  (14.908)
SBP, Week 24, n=99, 263 -1.97  (14.820) -3.94  (14.917)
SBP, Week 28, n=74, 211 -0.69  (14.663) -4.99  (14.557)
SBP, Week 32, n=67, 197 -1.46  (13.904) -5.61  (13.523)
SBP, Week 36, n=62, 186 -1.31  (13.803) -4.40  (14.842)
SBP, Week 40, n=59, 173 0.10  (13.605) -4.31  (13.941)
SBP, Week 44, n=59, 167 0.56  (11.689) -4.54  (13.794)
SBP, End of Treatment, n=238, 468 -2.03  (13.259) -3.98  (15.318)
SBP, 4-week FU, n=221, 426 -1.14  (14.095) -1.65  (15.122)
SBP, 12-week FU, n=207, 432 -0.11  (14.113) -0.86  (14.806)
SBP, 24-week FU, n=203, 398 1.10  (14.545) 0.25  (14.518)
DBP, Week 1, n=246, 491 -1.43  (9.235) -1.37  (8.224)
DBP, Week 2, n=242, 493 -1.55  (9.217) -1.86  (8.946)
DBP, Week 4, n=228, 485 -1.84  (9.726) -2.72  (9.467)
DBP, Week 6, n=206, 471 -2.16  (8.939) -2.95  (9.859)
DBP, Week 8, n=190, 472 -1.24  (9.517) -2.68  (9.901)
DBP, Week 12, n=175, 452 -1.31  (8.781) -3.23  (10.025)
DBP, Week 16, n=143, 403 -1.54  (9.684) -3.31  (9.899)
DBP, Week 20, n=133, 374 -0.93  (10.582) -3.08  (9.606)
DBP, Week 24, n=99, 263 -1.66  (10.207) -3.54  (9.313)
DBP, Week 28, n=74, 211 -1.23  (9.538) -3.42  (10.502)
DBP, Week 32, n=67, 197 -0.54  (10.445) -3.76  (9.527)
DBP, Week 36, n=62, 186 -0.74  (9.559) -3.59  (9.211)
DBP, Week 40, n=59, 173 0.34  (9.343) -3.32  (9.517)
DBP, Week 44, n=59, 167 0.92  (9.033) -3.77  (10.134)
DBP, End of Treatment, n=238, 468 -1.55  (9.174) -3.59  (10.254)
DBP, 4-week FU, n=221, 426 -0.83  (9.102) -2.20  (9.824)
DBP, 12-week FU, n=207, 432 -0.78  (10.253) -1.76  (9.903)
DBP, 24-week FU, n=203, 398 0.03  (9.814) -1.61  (9.339)
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)
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-2b 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 &gt;=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 244 490
Mean (Standard Deviation)
Unit of Measure: beats per minute
Week 1, n=244, 490 1.16  (8.358) -0.43  (8.629)
Week 2, n=242, 490 1.89  (8.510) 0.78  (9.644)
Week 4, n=227, 483 2.47  (9.464) 1.50  (9.739)
Week 6, n=205, 470 3.23  (9.158) 1.19  (8.708)
Week 8, n=190, 472 2.91  (9.751) 1.78  (9.227)
Week 12, n=174, 450 4.28  (10.188) 2.02  (9.539)
Week 16, n=143, 403 5.87  (9.975) 2.38  (10.419)
Week 20, n=132, 371 5.73  (9.688) 2.10  (9.530)
Week 24, n=99, 262 3.77  (9.912) 2.03  (9.399)
Week 28, n=74, 211 2.72  (10.038) 1.64  (10.328)
Week 32, n=67, 196 4.28  (8.281) 1.62  (9.676)
Week 36, n=62, 186 5.42  (10.109) 2.11  (10.205)
Week 40, n=59, 171 4.83  (8.919) 0.78  (9.895)
Week 44, n=59, 165 5.53  (11.005) 1.16  (8.846)
End of Treatment, n=237, 467 4.01  (10.606) 2.89  (11.134)
4-week FU, n=220, 422 4.27  (10.432) 2.11  (10.113)
12-week FU, n=206, 429 1.73  (9.707) 0.74  (9.955)
24-week FU, n=202, 395 0.14  (9.803) -1.90  (9.176)
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-2b 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 &gt;=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 248 495
Mean (Standard Deviation)
Unit of Measure: Kilograms (kg)
Week 1, n=248, 492 -0.65  (2.201) -0.68  (2.062)
Week 2, n=244, 495 -0.88  (1.983) -1.06  (2.809)
Week 4, n=229, 488 -1.30  (2.374) -1.30  (2.488)
Week 6, n=207, 476 -1.42  (2.464) -1.68  (2.652)
Week 8, n=191, 473 -1.89  (2.793) -2.11  (2.810)
Week 12, n=175, 453 -2.18  (2.985) -2.83  (3.440)
Week 16, n=145, 406 -2.37  (3.247) -3.32  (3.798)
Week 20, n=134, 378 -3.08  (3.684) -3.99  (4.040)
Week 24, n=99, 265 -4.04  (4.148) -4.75  (4.175)
Week 28, n=74, 212 -4.57  (4.749) -5.09  (5.016)
Week 32, n=67, 200 -4.50  (4.397) -5.52  (5.369)
Week 36, n=63, 188 -4.54  (4.739) -5.39  (7.476)
Week 40, n=59, 174 -4.99  (4.612) -5.87  (5.571)
Week 44, n=59, 168 -4.79  (5.475) -5.89  (5.661)
End of Treatment, n=240, 470 -3.28  (4.361) -4.69  (5.180)
4-week FU, n=223, 425 -2.78  (4.318) -3.84  (6.381)
12-week FU, n=210, 434 -1.98  (4.088) -2.99  (5.999)
24-week FU, n=205, 401 -1.36  (4.568) -1.51  (7.683)
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-2b 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 &gt;=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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 248 493
Mean (Standard Deviation)
Unit of Measure: Kilograms per meters squared (kg/m^2)
Week 1, n=248, 490 -0.23  (0.771) -0.23  (0.713)
Week 2, n=244, 493 -0.31  (0.691) -0.36  (0.921)
Week 4, n=229, 486 -0.46  (0.823) -0.45  (0.855)
Week 6, n=207, 474 -0.50  (0.871) -0.58  (0.893)
Week 8, n=191, 471 -0.66  (0.967) -0.73  (0.955)
Week 12, n=175, 451 -0.77  (1.055) -0.97  (1.167)
Week 16, n=145, 404 -0.85  (1.158) -1.15  (1.285)
Week 20, n=134, 376 -1.11  (1.324) -1.39  (1.377)
Week 24, n=99, 264 -1.46  (1.509) -1.66  (1.624)
Week 28, n=74, 211 -1.67  (1.731) -1.79  (1.733)
Week 32, n=67, 199 -1.64  (1.586) -1.94  (1.844)
Week 36, n=63, 187 -1.65  (1.703) -1.89  (2.651)
Week 40, n=59, 173 -1.81  (1.671) -2.09  (1.953)
Week 44, n=59, 167 -1.73  (2.007) -2.09  (1.942)
End of Treatment, n=240, 468 -1.16  (1.553) -1.64  (1.783)
4-week FU, n=223, 423 -0.98  (1.519) -1.35  (2.306)
12-week FU, n=210, 432 -0.70  (1.434) -1.06  (2.055)
24-week FU, n=205, 399 -0.47  (1.544) -0.53  (2.736)
Time Frame Adverse events (AEs) are reported for the Double-blind (DB) on-treatment + 30 days period (up to Study Week 52).
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 &lt;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 &lt;100 Gi/L, participants underwent dose escalation to 50 mg QD for 2 weeks. If platelet counts still remained &lt;100 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 &gt;=100 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 &gt;=100 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-2b 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 >=100 Gi/L) in combination with antiviral therapy (peginterferon alfa-2b 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   9/805 (1.12%)   49/252 (19.44%)   119/506 (23.52%) 
Blood and lymphatic system disorders       
Anemia  1  0/805 (0.00%)  2/252 (0.79%)  5/506 (0.99%) 
Thrombocytopenia  1  0/805 (0.00%)  1/252 (0.40%)  5/506 (0.99%) 
Anemia hemolytic autoimmune  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Febrile neutropenia  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Leukopenia  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Lymphadenitis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Neutropenia  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Pancytopenia  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Splenomegaly  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Cardiac disorders       
Angina pectoris  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Angina unstable  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Atrial fibrillation  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Cardiac arrest  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Coronary artery disease  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Myocardial infarction  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Cardio-respiratory arrest  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Eye disorders       
Cataract  1  0/805 (0.00%)  1/252 (0.40%)  9/506 (1.78%) 
Visual acuity reduced  1  0/805 (0.00%)  1/252 (0.40%)  2/506 (0.40%) 
Glaucoma  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Retinal hemorrhage  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Retinal vein thrombosis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Gastrointestinal disorders       
Gastric varices hemorrhage  1  1/805 (0.12%)  0/252 (0.00%)  0/506 (0.00%) 
Ascites  1  0/805 (0.00%)  2/252 (0.79%)  6/506 (1.19%) 
Gastrointestinal hemorrhage  1  0/805 (0.00%)  0/252 (0.00%)  5/506 (0.99%) 
Esophageal varices hemorrhage  1  0/805 (0.00%)  4/252 (1.59%)  4/506 (0.79%) 
Upper gastrointestinal hemorrhage  1  0/805 (0.00%)  1/252 (0.40%)  3/506 (0.59%) 
Anal fissure  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Diarrhea  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Hematemesis  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Hemorrhoids  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Vomiting  1  0/805 (0.00%)  1/252 (0.40%)  2/506 (0.40%) 
Abdominal adhesions  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Abdominal pain  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Abdominal pain upper  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Duodenal ulcer  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Gastritis erosive  1  0/805 (0.00%)  1/252 (0.40%)  1/506 (0.20%) 
Mechanical ileus  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Mesenteric vein thrombosis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Pancreatitis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Rectal hemorrhage  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Varices esophageal  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Caecitis  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Gastric ulcer  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Nausea  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
General disorders       
Pyrexia  1  0/805 (0.00%)  1/252 (0.40%)  2/506 (0.40%) 
Asthenia  1  0/805 (0.00%)  1/252 (0.40%)  1/506 (0.20%) 
Death  1  0/805 (0.00%)  1/252 (0.40%)  1/506 (0.20%) 
Generalized edema  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Induration  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Medical device complication  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Multi-organ failure  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Non-cardiac chest pain  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Edema peripheral  1  0/805 (0.00%)  1/252 (0.40%)  1/506 (0.20%) 
Sudden death  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Chest pain  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Malaise  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Multi-organ disorder  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Hepatobiliary disorders       
Hepatorenal syndrome  1  1/805 (0.12%)  0/252 (0.00%)  1/506 (0.20%) 
Hepatic failure  1  0/805 (0.00%)  0/252 (0.00%)  3/506 (0.59%) 
Hepatic cirrhosis  1  0/805 (0.00%)  1/252 (0.40%)  2/506 (0.40%) 
Jaundice cholestatic  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Portal vein thrombosis  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Cholecystitis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Cholecystitis acute  1  0/805 (0.00%)  1/252 (0.40%)  1/506 (0.20%) 
Hepatitis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Hepatorenal syndrome  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Jaundice  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Portal hypertension  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Autoimmune hepatitis  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Cholelithiasis  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Immune system disorders       
Amyloidosis  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Infections and infestations       
Arthritis bacterial  1  1/805 (0.12%)  0/252 (0.00%)  0/506 (0.00%) 
Pneumonia  1  1/805 (0.12%)  4/252 (1.59%)  7/506 (1.38%) 
Urinary tract infection  1  1/805 (0.12%)  2/252 (0.79%)  1/506 (0.20%) 
Sepsis  1  0/805 (0.00%)  0/252 (0.00%)  4/506 (0.79%) 
Cellulitis  1  0/805 (0.00%)  2/252 (0.79%)  2/506 (0.40%) 
Peritonitis bacterial  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Abdominal sepsis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Abscess limb  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Bronchitis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Campylobacter intestinal infection  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Clostridial infection  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Empyema  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Lobar pneumonia  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Peritoneal infection  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Pneumonia influenzal  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Pulmonary tuberculosis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Pyelonephritis acute  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Tonsillitis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Urosepsis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Viral pharyngitis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Abdominal wall abscess  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Actinomycotic pulmonary infection  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Anal abscess  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Anogenital warts  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Appendicitis  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Brain abscess  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Postoperative abscess  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Salmonella bacteremia  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Injury, poisoning and procedural complications       
Spinal compression fracture  1  1/805 (0.12%)  0/252 (0.00%)  0/506 (0.00%) 
Ankle fracture  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Cataract traumatic  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Pubis fracture  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Radius fracture  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Spinal fracture  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Tibia fracture  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Investigations       
Blood creatinine increased  1  1/805 (0.12%)  0/252 (0.00%)  0/506 (0.00%) 
Blood potassium decreased  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Metabolism and nutrition disorders       
Hyperkalemia  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Hypoglycemia  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Decreased appetite  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Diabetes mellitus  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Hyperglycemia  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Back pain  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Hepatic neoplasm malignant  1  1/805 (0.12%)  7/252 (2.78%)  22/506 (4.35%) 
Benign hepatic neoplasm  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Gastric cancer  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Hepatic neoplasm  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Lung squamous cell carcinoma stage unspecified  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Bile duct cancer  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Nervous system disorders       
Hepatic encephalopathy  1  0/805 (0.00%)  1/252 (0.40%)  9/506 (1.78%) 
Coma hepatic  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Cerebrovascular accident  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Coma  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Encephalopathy  1  0/805 (0.00%)  1/252 (0.40%)  1/506 (0.20%) 
Syncope  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Osmotic demyelination syndrome  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Psychiatric disorders       
Suicidal ideation  1  1/805 (0.12%)  0/252 (0.00%)  2/506 (0.40%) 
Depression  1  0/805 (0.00%)  2/252 (0.79%)  2/506 (0.40%) 
Abnormal behavior  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Confusional state  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Delirium  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Mental status changes  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Suicide attempt  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Affect lability  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Delirium tremens  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Depressed mood  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Insomnia  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Renal and urinary disorders       
Renal failure  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Acute prerenal failure  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Renal failure acute  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Nephrolithiasis  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Respiratory failure  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Acute respiratory failure  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Dyspnea  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Dyspnea exertional  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Oropharyngeal pain  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Pharyngeal ulceration  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Pneumonia aspiration  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Pulmonary embolism  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Asthma  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Epistaxis  1  0/805 (0.00%)  2/252 (0.79%)  0/506 (0.00%) 
Pneumonitis  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Skin and subcutaneous tissue disorders       
Intertrigo  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (0.00%) 
Vascular disorders       
Aortic stenosis  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Deep vein thrombosis  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Hypotension  1  0/805 (0.00%)  0/252 (0.00%)  2/506 (0.40%) 
Femoral artery occlusion  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Vasculitis  1  0/805 (0.00%)  0/252 (0.00%)  1/506 (0.20%) 
Phlebitis  1  0/805 (0.00%)  1/252 (0.40%)  0/506 (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   0/805 (0.00%)   226/252 (89.68%)   459/506 (90.71%) 
Blood and lymphatic system disorders       
Anemia  1  0/805 (0.00%)  90/252 (35.71%)  200/506 (39.53%) 
Neutropenia  1  0/805 (0.00%)  83/252 (32.94%)  139/506 (27.47%) 
Thrombocytopenia  1  0/805 (0.00%)  83/252 (32.94%)  61/506 (12.06%) 
Leukopenia  1  0/805 (0.00%)  32/252 (12.70%)  57/506 (11.26%) 
Gastrointestinal disorders       
Nausea  1  0/805 (0.00%)  38/252 (15.08%)  92/506 (18.18%) 
Diarrhea  1  0/805 (0.00%)  24/252 (9.52%)  92/506 (18.18%) 
Vomiting  1  0/805 (0.00%)  18/252 (7.14%)  41/506 (8.10%) 
Abdominal pain  1  0/805 (0.00%)  10/252 (3.97%)  31/506 (6.13%) 
Abdominal pain upper  1  0/805 (0.00%)  13/252 (5.16%)  28/506 (5.53%) 
Ascites  1  0/805 (0.00%)  6/252 (2.38%)  28/506 (5.53%) 
General disorders       
Pyrexia  1  0/805 (0.00%)  60/252 (23.81%)  141/506 (27.87%) 
Fatigue  1  0/805 (0.00%)  53/252 (21.03%)  124/506 (24.51%) 
Influenza like illness  1  0/805 (0.00%)  36/252 (14.29%)  100/506 (19.76%) 
Asthenia  1  0/805 (0.00%)  28/252 (11.11%)  86/506 (17.00%) 
Chills  1  0/805 (0.00%)  32/252 (12.70%)  72/506 (14.23%) 
Irritability  1  0/805 (0.00%)  11/252 (4.37%)  34/506 (6.72%) 
Edema peripheral  1  0/805 (0.00%)  3/252 (1.19%)  36/506 (7.11%) 
Injection site erythema  1  0/805 (0.00%)  14/252 (5.56%)  22/506 (4.35%) 
Hepatobiliary disorders       
Hyperbilirubinemia  1  0/805 (0.00%)  11/252 (4.37%)  42/506 (8.30%) 
Infections and infestations       
Urinary tract infection  1  0/805 (0.00%)  13/252 (5.16%)  29/506 (5.73%) 
Investigations       
Weight decreased  1  0/805 (0.00%)  17/252 (6.75%)  49/506 (9.68%) 
White blood cell count decreased  1  0/805 (0.00%)  18/252 (7.14%)  42/506 (8.30%) 
Hemoglobin decreased  1  0/805 (0.00%)  16/252 (6.35%)  34/506 (6.72%) 
Blood bilirubin increased  1  0/805 (0.00%)  7/252 (2.78%)  36/506 (7.11%) 
Platelet count decreased  1  0/805 (0.00%)  14/252 (5.56%)  27/506 (5.34%) 
Metabolism and nutrition disorders       
Decreased appetite  1  0/805 (0.00%)  36/252 (14.29%)  94/506 (18.58%) 
Musculoskeletal and connective tissue disorders       
Myalgia  1  0/805 (0.00%)  22/252 (8.73%)  51/506 (10.08%) 
Arthralgia  1  0/805 (0.00%)  20/252 (7.94%)  33/506 (6.52%) 
Muscle spasms  1  0/805 (0.00%)  14/252 (5.56%)  36/506 (7.11%) 
Nervous system disorders       
Headache  1  0/805 (0.00%)  50/252 (19.84%)  95/506 (18.77%) 
Dizziness  1  0/805 (0.00%)  13/252 (5.16%)  40/506 (7.91%) 
Psychiatric disorders       
Insomnia  1  0/805 (0.00%)  27/252 (10.71%)  72/506 (14.23%) 
Depression  1  0/805 (0.00%)  19/252 (7.54%)  47/506 (9.29%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/805 (0.00%)  26/252 (10.32%)  64/506 (12.65%) 
Dyspnea  1  0/805 (0.00%)  10/252 (3.97%)  36/506 (7.11%) 
Epistaxis  1  0/805 (0.00%)  16/252 (6.35%)  26/506 (5.14%) 
Skin and subcutaneous tissue disorders       
Pruritus  1  0/805 (0.00%)  34/252 (13.49%)  71/506 (14.03%) 
Alopecia  1  0/805 (0.00%)  12/252 (4.76%)  50/506 (9.88%) 
Rash  1  0/805 (0.00%)  10/252 (3.97%)  38/506 (7.51%) 
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: NCT00529568    
Other Study ID Numbers: TPL108390
First Submitted: September 12, 2007
First Posted: September 14, 2007
Results First Submitted: April 19, 2012
Results First Posted: May 17, 2012
Last Update Posted: November 5, 2013