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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00516321

Collaborator

(none)

687

Enrollment

191

Locations

Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the ability of eltrombopag to maintain a platelet count sufficient to facilitate initiation of antiviral therapy, to minimise antiviral therapy dose reductions and to avoid permanent discontinuation of antiviral therapy. The clinical benefit of eltrombopag will be measured by the proportion of subjects who are able to achieve a Sustained Virological Response (SVR).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: eltrombopag Drug: placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

687 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomised, Placebo-controlled, Multi-centre Study to Assess the Efficacy and Safety of Eltrombopag in Thrombocytopenic Subjects With Hepatitis C Virus (HCV) Infection Who Are Otherwise Eligible to Initiate Antiviral Therapy (Peginterferon Alfa-2a Plus Ribavirin

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Apr 1, 2011

Actual Study Completion Date :

May 1, 2011

Outcome Measures

Primary Outcome Measures

Number of Participants With Sustained Virologic Response (SVR) in the Double-blind (DB) Antiviral Treatment Phase [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)]
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.

Secondary Outcome Measures

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 [From Baseline up to Week 9 in the OL Phase]
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.
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 [From Baseline up to Week 9 in the OL Phase]
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.
Median Platelet Count at the Indicated Time Points During the OL Phase [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)]
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.
Median Platelet Count at the Indicated Time Points During the DB Phase [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)]
Blood taken from peripheral blood vessels was used for the measurement of platelet counts.
Number of Participants in the Indicated Categories for Minimum Platelet Count With Antiviral Therapy During the DB Phase [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)]
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.
Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) During the DB Phase [From Baseline up to Week 12]
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.
Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) During the DB Phase [From Baseline up to Week 12]
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.
Number of Participants With End of Treatment Response (ETR) and Sustained Virological Response at Week 12 of Follow-up (SVR12) During the DB Phase [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)]
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.
Number of Participants in the Indicated Categories for Antiviral Therapy Dose Reductions in the DB Phase [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)]
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 to First Dose Reduction of Peginterferon Alfa-2a and Ribavirin Therapy in the DB Phase [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)]
Time to first dose reduction was calculated as the time period from the first dose to the first dose reduction.
Number of Participants With the Indicated Levels of Peginterferon Dose Reductions in the DB Phase [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)]
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.
Number of Participants Who Prematurely Discontinued Antiviral Therapy in the DB Phase [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)]
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.
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 [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)]
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.
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 [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)]
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.
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 [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)]
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.
Number of Participants in the Indicated Categories for Cataract Event During the DB Phase, Per Clinical Events Committee (CEC) Adjudication During the DB Phase [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)]
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.
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 [DB Phase: Antiviral BL (up to Week 10); End of Treatment (up to Week 52); and 24-week FU (up to Week 72)]
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.
Number of Participants With CS and NCS Change From Baseline for 12-lead ECG at the Indicated Time Points During the DB Phase [End of Treatment (up to Week 52); and 24-week FU (up to Week 72)]
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.
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During the DB Phase [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)]
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.
Mean Change From Baseline in Heart Rate at the Indicated Time Points During the DB Phase [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)]
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.
Mean Change From Baseline in Weight at the Indicated Time Points During the DB Phase [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)]
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.
Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points During the DB Phase [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)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female subjects, >18 years Evidence of chronic hepatitis C virus (HCV) infection Subjects who are appropriate candidates for peginterferon (pegIFN) and ribavirin antiviral therapy A platelet count of <75,000/mcL Haemoglobin >11.0g/dL for men or >10.0g/dL for women Absolute neutrophil count (ANC) >750/mm3 and no history of infections associated with neutropenia Creatinine clearance >50mL/minute All fertile males and females must use two forms of effective contraception between them during treatment and during the 24 weeks after treatment end Subject is able to understand, consent and comply with protocol requirements and instructions and is likely to complete the study as planned

Exclusion criteria:

Non-responders to previous treatment with pegIFN and ribavirin who failed to achieve a sustained virologic response (SVR) for reasons other than thrombocytopenia, despite an optimal course (dose and duration) of combination therapy with pegIFN and ribavirin Decompensated liver disease, e.g. Child-Pugh score >6 or history of ascites or hepatic encephalopathy or current evidence of ascites Known hypersensitivity, intolerance or allergy to interferon (IFN), ribavirin, eltrombopag or any of their ingredients Serious cardiac, cerebrovascular, or pulmonary disease that would preclude treatment with pegIFN and ribavirin

Subjects with a history of any one of the following:

Suicide attempt or hospitalisation for depression in the past 5 years Any current severe or poorly controlled psychiatric disorder

The following subjects are eligible for study participation, but must be assessed and followed (if recommended) by a mental health professional:

Subjects who have had a severe or poorly controlled psychiatric disorder more than 6 months ago but less than 5 years ago
Seizure disorder that has not been well controlled History of clinically significant bleeding from oesophageal or gastric varices Subjects with haemoglobinopathies, e.g. sickle cell anaemia, thalassemia major Any prior history of arterial or venous thrombosis AND two or more of the following risk factors: hereditary thrombophilic disorders (e.g. Factor V Leiden, antithrombin III (ATIII) deficiency, etc), hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer Pre-existing cardiac disease (New York Heart Association (NYHA) Grade III/IV), or arrhythmias known to involve the risk of thromboembolic events, or corrected QT interval (QTc) >450 msec Evidence of hepatocellular carcinoma Laboratory evidence of infection with human immunodeficiency virus (HIV) or active Hepatitis B Virus (HBV) infection Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin Therapy with any anti-neoplastic or immuno-modulatory treatment <6 months prior to the first dose of eltrombopag Subjects who have had a malignancy diagnosed and/or treated within the past 5 years, except for subjects with localised basal or squamous cell carcinoma treated by local excision or subjects with malignancies who have been adequately treated and, in the opinion of the oncologist, have an excellent chance of cancer-free survival Pregnant or nursing women Males with a female partner who is pregnant History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation programme) Treatment with an investigational drug or IFN within 30 days or 5 half-lives (whichever is longer) of the screening visit History of platelet clumping that prevents reliable measurement of platelet counts History of major organ transplantation with an existing functional graft Thyroid dysfunction not adequately controlled Subjects planning to have cataract surgery Evidence of portal vein thrombosis on abdominal imaging within 3 months of the baseline visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35294-0005
2	GSK Investigational Site	Tucson	Arizona	United States	85750
3	GSK Investigational Site	Little Rock	Arkansas	United States	72205-7199
4	GSK Investigational Site	La Jolla	California	United States	92037
5	GSK Investigational Site	Los Angeles	California	United States	90017
6	GSK Investigational Site	Los Angeles	California	United States	90048
7	GSK Investigational Site	San Clemente	California	United States	92673
8	GSK Investigational Site	Aurora	Colorado	United States	80045
9	GSK Investigational Site	New Haven	Connecticut	United States	06520
10	GSK Investigational Site	Washington	District of Columbia	United States	20010
11	GSK Investigational Site	Washington	District of Columbia	United States	20307
12	GSK Investigational Site	Bradenton	Florida	United States	34209
13	GSK Investigational Site	Gainsville	Florida	United States	32610
14	GSK Investigational Site	Miami	Florida	United States	33136
15	GSK Investigational Site	Orlando	Florida	United States	32803
16	GSK Investigational Site	Atlanta	Georgia	United States	30309
17	GSK Investigational Site	Honolulu	Hawaii	United States	96817
18	GSK Investigational Site	Louisville	Kentucky	United States	40202
19	GSK Investigational Site	Baltimore	Maryland	United States	21202
20	GSK Investigational Site	Burlington	Massachusetts	United States	01805
21	GSK Investigational Site	Worcester	Massachusetts	United States	01655
22	GSK Investigational Site	Ann Arbor	Michigan	United States	48109
23	GSK Investigational Site	Detroit	Michigan	United States	48201
24	GSK Investigational Site	Jackson	Mississippi	United States	39202
25	GSK Investigational Site	St. Louis	Missouri	United States	63110
26	GSK Investigational Site	Bronx	New York	United States	10468
27	GSK Investigational Site	Manhasset	New York	United States	11030
28	GSK Investigational Site	New York	New York	United States	10021
29	GSK Investigational Site	Rochester	New York	United States	14642
30	GSK Investigational Site	Syracuse	New York	United States	13210
31	GSK Investigational Site	Valhalla	New York	United States	10595
32	GSK Investigational Site	Asheville	North Carolina	United States	28801
33	GSK Investigational Site	Durham	North Carolina	United States	27705
34	GSK Investigational Site	Tulsa	Oklahoma	United States	74104
35	GSK Investigational Site	Portland	Oregon	United States	97239
36	GSK Investigational Site	Hershey	Pennsylvania	United States	17033-0850
37	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104
38	GSK Investigational Site	Jackson	Tennessee	United States	38301
39	GSK Investigational Site	Nashville	Tennessee	United States	37203
40	GSK Investigational Site	Nashville	Tennessee	United States	37205
41	GSK Investigational Site	Nashville	Tennessee	United States	37212
42	GSK Investigational Site	Galveston	Texas	United States	77555-0435
43	GSK Investigational Site	Houston	Texas	United States	77030
44	GSK Investigational Site	San Antonio	Texas	United States	78215
45	GSK Investigational Site	Charlottesville	Virginia	United States	22908
46	GSK Investigational Site	Fairfax	Virginia	United States	22031
47	GSK Investigational Site	Richmond	Virginia	United States	23249
48	GSK Investigational Site	Garran	Australian Capital Territory	Australia	2606
49	GSK Investigational Site	Camperdown	New South Wales	Australia	2050
50	GSK Investigational Site	Randwick	New South Wales	Australia	2031
51	GSK Investigational Site	Fitzroy	Victoria	Australia	3065
52	GSK Investigational Site	Heidelberg	Victoria	Australia	3084
53	GSK Investigational Site	Melbourne	Victoria	Australia	3168
54	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
55	GSK Investigational Site	Bruxelles		Belgium	1200
56	GSK Investigational Site	Edegem		Belgium	2650
57	GSK Investigational Site	Gent		Belgium	9000
58	GSK Investigational Site	Leuven		Belgium	3000
59	GSK Investigational Site	Campinas	São Paulo	Brazil	13083-888
60	GSK Investigational Site	São Paulo		Brazil	04023900
61	GSK Investigational Site	Calgary	Alberta	Canada	T2N 4Z6
62	GSK Investigational Site	Victoria	British Columbia	Canada	V8V 3P9
63	GSK Investigational Site	Winnipeg	Manitoba	Canada	R3E 3P4
64	GSK Investigational Site	Barrie	Ontario	Canada	L4M 7G1
65	GSK Investigational Site	Hamilton	Ontario	Canada	L8L 2X2
66	GSK Investigational Site	Hamilton	Ontario	Canada	L8N 4A6
67	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
68	GSK Investigational Site	Ottawa	Ontario	Canada	K1N 6N5
69	GSK Investigational Site	Toronto	Ontario	Canada	M5G 1X5
70	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2C4
71	GSK Investigational Site	Toronto	Ontario	Canada	M5T 2S8
72	GSK Investigational Site	Toronto	Ontario	Canada	M6H 3M1
73	GSK Investigational Site	Montreal	Quebec	Canada	H2X 2P4
74	GSK Investigational Site	Montreal	Quebec	Canada	H2X 3J4
75	GSK Investigational Site	Praha 4		Czech Republic	140 21
76	GSK Investigational Site	Praha 6		Czech Republic	169 02
77	GSK Investigational Site	Besançon		France	25030
78	GSK Investigational Site	Dijon cedex		France	21019
79	GSK Investigational Site	Marseille		France	13385
80	GSK Investigational Site	Montpellier		France	34295
81	GSK Investigational Site	Nice		France	06202
82	GSK Investigational Site	Pessac Cedex		France	33604
83	GSK Investigational Site	Strasbourg		France	67091
84	GSK Investigational Site	Toulouse cedex 9		France	31059
85	GSK Investigational Site	Toulouse		France	31300
86	GSK Investigational Site	Freiburg	Baden-Wuerttemberg	Germany	79106
87	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg	Germany	69120
88	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg	Germany	70197
89	GSK Investigational Site	Ulm	Baden-Wuerttemberg	Germany	89081
90	GSK Investigational Site	Deggendorf	Bayern	Germany	94469
91	GSK Investigational Site	Hof/Saale	Bayern	Germany	95028
92	GSK Investigational Site	Muenchen	Bayern	Germany	81377
93	GSK Investigational Site	Regensburg	Bayern	Germany	93053
94	GSK Investigational Site	Wuerzburg	Bayern	Germany	97080
95	GSK Investigational Site	Beeskow	Brandenburg	Germany	15848
96	GSK Investigational Site	Frankfurt	Hessen	Germany	60590
97	GSK Investigational Site	Kassel	Hessen	Germany	34127
98	GSK Investigational Site	Goettingen	Niedersachsen	Germany	37075
99	GSK Investigational Site	Hannover	Niedersachsen	Germany	30159
100	GSK Investigational Site	Hannover	Niedersachsen	Germany	30625
101	GSK Investigational Site	Aachen	Nordrhein-Westfalen	Germany	52074
102	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44787
103	GSK Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53127
104	GSK Investigational Site	Dortmund	Nordrhein-Westfalen	Germany	44263
105	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen	Germany	40225
106	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45122
107	GSK Investigational Site	Herne	Nordrhein-Westfalen	Germany	44623
108	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50937
109	GSK Investigational Site	Leverkusen	Nordrhein-Westfalen	Germany	51375
110	GSK Investigational Site	Muenster	Nordrhein-Westfalen	Germany	48143
111	GSK Investigational Site	Siegen	Nordrhein-Westfalen	Germany	57072
112	GSK Investigational Site	Mainz	Rheinland-Pfalz	Germany	55131
113	GSK Investigational Site	Halle	Sachsen-Anhalt	Germany	06120
114	GSK Investigational Site	Magdeburg	Sachsen-Anhalt	Germany	39120
115	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
116	GSK Investigational Site	Leipzig	Sachsen	Germany	04129
117	GSK Investigational Site	Berlin		Germany	12203
118	GSK Investigational Site	Berlin		Germany	13353
119	GSK Investigational Site	Pokfulam		Hong Kong
120	GSK Investigational Site	Bangalore		India
121	GSK Investigational Site	Chennai		India	600 096
122	GSK Investigational Site	Mumbai		India	400036
123	GSK Investigational Site	Haifa		Israel	31096
124	GSK Investigational Site	Jerusalem		Israel	91120
125	GSK Investigational Site	Petach Tikva		Israel	49100
126	GSK Investigational Site	Safed		Israel	13110
127	GSK Investigational Site	Tel Aviv		Israel	64239
128	GSK Investigational Site	Catanzaro	Calabria	Italy	88100
129	GSK Investigational Site	Avellino	Campania	Italy	83100
130	GSK Investigational Site	Bologna	Emilia-Romagna	Italy	40138
131	GSK Investigational Site	Roma	Lazio	Italy	00133
132	GSK Investigational Site	Genova	Liguria	Italy	16132
133	GSK Investigational Site	Brescia	Lombardia	Italy	25123
134	GSK Investigational Site	Milano	Lombardia	Italy	20132
135	GSK Investigational Site	Milano	Lombardia	Italy	20157
136	GSK Investigational Site	Bari	Puglia	Italy	70124
137	GSK Investigational Site	San Giovanni Rotondo (FG)	Puglia	Italy	71013
138	GSK Investigational Site	Palermo	Sicilia	Italy	90127
139	GSK Investigational Site	Busan		Korea, Republic of	614-735
140	GSK Investigational Site	Incheon		Korea, Republic of	400-711
141	GSK Investigational Site	Seoul		Korea, Republic of	135-710
142	GSK Investigational Site	Amsterdam		Netherlands	1081 HV
143	GSK Investigational Site	Nijmegen		Netherlands	6525 GA
144	GSK Investigational Site	Rotterdam		Netherlands	3015 CE
145	GSK Investigational Site	Lahore		Pakistan	54000
146	GSK Investigational Site	Lahore		Pakistan	54600
147	GSK Investigational Site	Bydgoszcz		Poland	85-030
148	GSK Investigational Site	Chorzow		Poland	41-500
149	GSK Investigational Site	Kielce		Poland	25-317
150	GSK Investigational Site	Szczecin		Poland	71-455
151	GSK Investigational Site	Wroclaw		Poland	51-149
152	GSK Investigational Site	Ponce		Puerto Rico	00717
153	GSK Investigational Site	San Juan		Puerto Rico	00927
154	GSK Investigational Site	Bucharest		Romania	021105
155	GSK Investigational Site	Constanta		Romania	900708
156	GSK Investigational Site	Moscow		Russian Federation	110020
157	GSK Investigational Site	Moscow		Russian Federation	129110
158	GSK Investigational Site	Mosocow		Russian Federation	117593
159	GSK Investigational Site	Smolensk		Russian Federation	214018
160	GSK Investigational Site	Bratislava		Slovakia	811 07
161	GSK Investigational Site	Bratislava		Slovakia	833 05
162	GSK Investigational Site	Kosice		Slovakia	041 66
163	GSK Investigational Site	Martin		Slovakia	036 59
164	GSK Investigational Site	Barcelona		Spain	08025
165	GSK Investigational Site	Granada		Spain	18012
166	GSK Investigational Site	L'Hospitalet de Llobregat. Barcelona		Spain	08907
167	GSK Investigational Site	La Coruña		Spain	15006
168	GSK Investigational Site	Madrid		Spain	28006
169	GSK Investigational Site	Madrid		Spain	28007
170	GSK Investigational Site	Madrid		Spain	28029
171	GSK Investigational Site	Madrid		Spain	28034
172	GSK Investigational Site	San Sebastián		Spain	20014
173	GSK Investigational Site	Sevilla		Spain	41014
174	GSK Investigational Site	Valencia		Spain	46010
175	GSK Investigational Site	Kaohsiung		Taiwan	80708
176	GSK Investigational Site	Taichung		Taiwan	407
177	GSK Investigational Site	Tainan		Taiwan	704
178	GSK Investigational Site	Taipei		Taiwan	100
179	GSK Investigational Site	Bangkok		Thailand	10330
180	GSK Investigational Site	Bangkok		Thailand	10700
181	GSK Investigational Site	Chiangmai		Thailand	50200
182	GSK Investigational Site	Khon Kaen		Thailand	40002
183	GSK Investigational Site	Songkla		Thailand	90110
184	GSK Investigational Site	Donetsk		Ukraine	83114
185	GSK Investigational Site	Kyiv		Ukraine	01030
186	GSK Investigational Site	Kyiv		Ukraine	04112
187	GSK Investigational Site	Vinnytsia		Ukraine	21021
188	GSK Investigational Site	Glasgow	Lanarkshire	United Kingdom	G12 0YN
189	GSK Investigational Site	London		United Kingdom	NW3 2QG
190	GSK Investigational Site	London		United Kingdom	W2 1NY
191	GSK Investigational Site	Plymouth		United Kingdom	PL6 8DH

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00516321

Other Study ID Numbers:

TPL103922

First Posted:

Aug 15, 2007

Last Update Posted:

Nov 5, 2013

Last Verified:

Aug 1, 2012

Keywords provided by GlaxoSmithKline

Hepatitis C-related thrombocytopenia

peginterferon alfa-2a

Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Eltrombopag: OL Phase	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase
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
Period Title: Open-label (OL) Pre-Antiviral Treatment
STARTED	0	232	450
COMPLETED	0	197	396
NOT COMPLETED	0	35	54

Baseline Characteristics

Arm/Group Title	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase	Total
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 Participants	232	450	682
Age (Years) [Mean (Standard Deviation) ]
Years	51.4 (8.52)	52.1 (8.35)	51.9 (8.41)
Sex: Female, Male (Count of Participants)
Female	73 31.5%	186 41.3%	259 38%
Male	159 68.5%	264 58.7%	423 62%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	6 2.6%	12 2.7%	18 2.6%
American Indian/Alaska Native	3 1.3%	2 0.4%	5 0.7%
Central/South Asian Heritage	14 6%	39 8.7%	53 7.8%
Japanese/East Asian Heritage/South East Asian	43 18.5%	68 15.1%	111 16.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.2%	1 0.1%
White	166 71.6%	326 72.4%	492 72.1%
Asian and White	0 0%	1 0.2%	1 0.1%
Native Hawaiian/ Other Pacific Islander and White	0 0%	1 0.2%	1 0.1%
Number of participants categorized into the indicated genotype for Hepatitic C Virus (HCV) (participants) [Number]
Genotype 1	149 64.2%	292 64.9%	441 64.7%
Genotype 2	22 9.5%	27 6%	49 7.2%
Genotype 3	54 23.3%	115 25.6%	169 24.8%
Genotype 4	5 2.2%	11 2.4%	16 2.3%
Genotype 5	0 0%	0 0%	0 0%
Genotype 6	2 0.9%	4 0.9%	6 0.9%
Genotype 7	0 0%	0 0%	0 0%
Missing Data	0 0%	1 0.2%	1 0.1%
Number of participants categorized into the indicated Child-Pugh (CP) Class (participants) [Number]
Class A	217 93.5%	424 94.2%	641 94%
Class B	15 6.5%	25 5.6%	40 5.9%
Class C	0 0%	0 0%	0 0%
Missing Data	0 0%	1 0.2%	1 0.1%
Number of participants with or without previous interferon (IFN) use (participants) [Number]
Naïve	152 65.5%	307 68.2%	459 67.3%
Experienced	80 34.5%	143 31.8%	223 32.7%
Number of participants with the indicated FibroTest/Acti Test (FibroSURE) score (participants) [Number]
Score: F0/F1/F2	23 9.9%	37 8.2%	60 8.8%
Score: F3/F4	185 79.7%	354 78.7%	539 79%
Missing	24 10.3%	59 13.1%	83 12.2%
Number of participants with normal or elevated Baseline values for Alanine Aminotransferase (ALT) (participants) [Number]
Normal	54 23.3%	103 22.9%	157 23%
Elevated	178 76.7%	347 77.1%	525 77%
Baseline HCV Ribonucleic Acid (RNA) (International Units per milliliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [International Units per milliliter]	1880278.4 (3395777.02)	1870562.1 (3080918.03)	1873862.8 (3188864.74)
Baseline Platelet Count (Giga (10^9) cells per liter (Gi/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Giga (10^9) cells per liter (Gi/L)]	57.40 (12.890)	56.87 (13.603)	57.05 (13.357)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Sustained Virologic Response (SVR) in the Double-blind (DB) Antiviral Treatment Phase
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)

Outcome Measure Data

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
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).
Measure Participants	232	450
Number [participants]	33 14.2%	104 23.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Antiviral Therapy: DB Phase, Eltrombopag+Antiviral Therapy: DB Phase
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

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

Method of Estimation	Estimation Parameter	Percentage difference in SVR
	Estimated Value	7.9
	Confidence Interval	(2-Sided) 95% 2.4 to 13.4
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who had received study drug in the OL Phase

Arm/Group Title	Eltrombopag: OL Phase
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.
Measure Participants	715
Number [participants]	691 297.8%

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
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

Outcome Measure Data

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
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.
Measure Participants	680
25 mg	451 194.4%
50 mg	176 75.9%
75 mg	39 16.8%
100 mg	14 6%

4. Secondary Outcome

Title	Median Platelet Count at the Indicated Time Points During the OL Phase
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)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	Eltrombopag: OL Phase
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.
Measure Participants	712
Baseline, n=712	59.00
Day 1, n=620	59.00
Week 1, n=703	77.00
Week 2, n=426	89.00
Week 3, n=179	83.00
Week 4, n=98	83.00
Week 5, n=56	77.00
Week 6, n=35	79.00
Week 7, n=29	77.00
Week 8, n=18	83.00
Week 9, n=7	70.00
Antiviral Baseline, n=48	130.00
End of Treatment/Withdrawal, n=18	63.00
Last on Treatment, n=30	75.00
4 Week Follow-Up, n=15	44.00
12 Week Follow-Up, n=16	38.00
24 Week Follow-Up, n=15	38.00

5. Secondary Outcome

Title	Median Platelet Count at the Indicated Time Points During the DB Phase
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)

Outcome Measure Data

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
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).
Measure Participants	232	447
Baseline, n=208, 387	128.00	133.00
Week 1, n=227, 443	112.00	115.00
Week 2, n=227, 438	79.00	111.00
Week 4, n=218, 430	43.50	90.00
Week 6, n=197, 423	40.00	89.00
Week 8, n=189, 414	41.00	86.00
Week 12, n=165, 404	44.00	91.50
Week 16, n=141, 377	43.00	93.00
Week 20, n=135, 363	44.00	89.00
Week 24, n=89, 248	43.00	92.00
Week 28, n=73, 202	45.00	89.50
Week 32, n=69, 183	44.40	91.00
Week 36, n=68, 173	44.50	91.00
Week 40, n=64, 169	44.00	93.00
Week 44, n=65, 168	48.00	93.50
End of Treatment/Withdrawal, n=212, 419	40.00	90.00
Last on Treatment, n=232, 447	40.00	90.00
4 Week Follow-Up, n=205, 400	54.00	82.00
12 Week Follow-Up, n=196, 396	56.00	67.00
24 Week Follow-Up, n=193, 391	56.00	60.00

6. Secondary Outcome

Title	Number of Participants in the Indicated Categories for Minimum Platelet Count With Antiviral Therapy During the DB Phase
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)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase
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).
Measure Participants	232	450
<25 Gi/L	63 27.2%	12 2.7%
>=25 to <50 Gi/L	135 58.2%	125 27.8%
>=50 to <90 Gi/L	19 8.2%	245 54.4%
>=90 to <150 Gi/L	11 4.7%	58 12.9%
>=150 to <200 Gi/L	2 0.9%	6 1.3%
>=200 to <400 Gi/L	2 0.9%	1 0.2%
>=400 Gi/L	0 0%	0 0%
Missing	0 0%	3 0.7%

7. Secondary Outcome

Title	Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) During the DB Phase
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

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase
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).
Measure Participants	232	450
RVR	39 16.8%	73 16.2%
eRVR	28 12.1%	68 15.1%

8. Secondary Outcome

Title	Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) During the DB Phase
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

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase
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).
Measure Participants	232	450
EVR	115 49.6%	297 66%
cEVR	60 25.9%	187 41.6%

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
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)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase
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).
Measure Participants	232	450
ETR	86 37.1%	214 47.6%
SVR12	36 15.5%	347 77.1%

10. Secondary Outcome

Title	Number of Participants in the Indicated Categories for Antiviral Therapy Dose Reductions in the DB Phase
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)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase
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).
Measure Participants	232	450
0	65 28%	195 43.3%
1	57 24.6%	93 20.7%
2	55 23.7%	56 12.4%
3	26 11.2%	49 10.9%
>3	29 12.5%	57 12.7%

11. Secondary Outcome

Title	Time to First Dose Reduction of Peginterferon Alfa-2a and Ribavirin Therapy in the DB Phase
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)

Outcome Measure Data

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
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).
Measure Participants	163	193
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
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)

Outcome Measure Data

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
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).
Measure Participants	232	450
180 to 135 mcg	73 31.5%	121 26.9%
180 to 90 mcg	94 40.5%	82 18.2%
180 to 45 mcg	2 0.9%	0 0%
135 to 90 mcg	55 23.7%	64 14.2%
135 to 45 mcg	2 0.9%	0 0%
90 to 45 mcg	18 7.8%	12 2.7%

13. Secondary Outcome

Title	Number of Participants Who Prematurely Discontinued Antiviral Therapy in the DB Phase
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)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase
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).
Measure Participants	232	450
Number [participants]	129 55.6%	184 40.9%

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
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)

Outcome Measure Data

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
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).
Measure Participants	99	181
SVR, rs12979860 (CC), R; n=12, 36	5 2.2%	18 4%
SVR, rs12979860 (CC), NR; n=99, 168	21 9.1%	38 8.4%
SVR, rs12979860 (CT), R; n=12, 36	6 2.6%	17 3.8%
SVR, rs12979860 (CT), NR; n=99, 168	63 27.2%	95 21.1%
SVR, rs12979860 (TT), R; n=12, 36	1 0.4%	1 0.2%
SVR, rs12979860 (TT), NR; n=99, 168	15 6.5%	35 7.8%
SVR, rs8099917 (TT), R; n=12, 36	7 3%	26 5.8%
SVR, rs8099917 (TT), NR; n=99, 166	50 21.6%	70 15.6%
SVR, rs8099917 (GT), R; n=12, 36	4 1.7%	9 2%
SVR, rs8099917 (GT), NR; n=99, 166	42 18.1%	75 16.7%
SVR, rs8099917 (GG), R; n=12, 36	1 0.4%	1 0.2%
SVR, rs8099917 (GG), NR; n=99, 166	7 3%	21 4.7%
RVR, rs12979860 (CC), R; n=16, 23	7 3%	12 2.7%
RVR, rs12979860 (CC), NR; n=95, 181	19 8.2%	44 9.8%
RVR, rs12979860 (CT), R; n=16, 23	7 3%	10 2.2%
RVR, rs12979860 (CT), NR; n=95, 181	62 26.7%	102 22.7%
RVR, rs12979860 (TT), R; n=16, 23	2 0.9%	1 0.2%
RVR, rs12979860 (TT), NR; n=95, 181	14 6%	35 7.8%
RVR, rs8099917 (TT), R, n=16, 23	10 4.3%	14 3.1%
RVR, rs8099917 (TT), NR; n=95, 179	47 20.3%	82 18.2%
RVR, rs8099917 (GT), R; n=16, 23	4 1.7%	9 2%
RVR, rs8099917 (GT), NR; n=95, 179	42 18.1%	75 16.7%
RVR, rs8099917 (GG), R; n=16, 23	2 0.9%	0 0%
RVR, rs8099917 (GG), NR; n=95, 179	6 2.6%	22 4.9%

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
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)

Outcome Measure Data

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
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).
Measure Participants	232	449
Calcium (hypocalcemia), Any Grade Increase	173 74.6%	343 76.2%
Calcium (hypocalcemia), Increase to G1	127 54.7%	211 46.9%
Calcium (hypocalcemia), Increase to G2	45 19.4%	126 28%
Calcium (hypocalcemia), Increase to G3	1 0.4%	4 0.9%
Calcium (hypocalcemia), Increase to G4	0 0%	2 0.4%
Calcium (hypercalcemia), Any Grade Increase	1 0.4%	5 1.1%
Calcium (hypercalcemia), Increase to G1	0 0%	4 0.9%
Calcium (hypercalcemia), Increase to G2	1 0.4%	1 0.2%
Calcium (hypercalcemia), Increase to G3	0 0%	0 0%
Calcium (hypercalcemia), Increase to G4	0 0%	0 0%
Glu. (hypoglycemia), Any Grade Increase	23 9.9%	58 12.9%
Glu. (hypoglycemia), Increase to G1	14 6%	30 6.7%
Glu. (hypoglycemia), Increase to G2	6 2.6%	22 4.9%
Glu. (hypoglycemia), Increase to G3	1 0.4%	4 0.9%
Glu. (hypoglycemia), Increase to G4	2 0.9%	2 0.4%
Glu. (hyperglycemia), Any Grade Increase	111 47.8%	239 53.1%
Glu. (hyperglycemia), Increase to G1	28 12.1%	61 13.6%
Glu. (hyperglycemia), Increase to G2	62 26.7%	148 32.9%
Glu. (hyperglycemia), Increase to G3	19 8.2%	29 6.4%
Glu. (hyperglycemia), Increase to G4	2 0.9%	1 0.2%
Pot. (hyperkalemia), Any Grade Increase	6 2.6%	10 2.2%
Pot. (hyperkalemia), Increase to G1	2 0.9%	6 1.3%
Pot. (hyperkalemia), Increase to G2	1 0.4%	2 0.4%
Pot. (hyperkalemia), Increase to G3	1 0.4%	1 0.2%
Pot. (hyperkalemia), Increase to G4	2 0.9%	1 0.2%
Pot. (hypokalemia), Any Grade Increase	33 14.2%	58 12.9%
Pot. (hypokalemia), Increase to G1	29 12.5%	53 11.8%
Pot. (hypokalemia), Increase to G2	4 1.7%	5 1.1%
Pot. (hypokalemia), Increase to G3	0 0%	0 0%
Pot. (hypokalemia), Increase to G4	0 0%	0 0%
Sod. (hypernatremia), Any Grade Increase	9 3.9%	12 2.7%
Sod. (hypernatremia), Increase to G1	9 3.9%	11 2.4%
Sod. (hypernatremia), Increase to G2	0 0%	0 0%
Sod. (hypernatremia), Increase to G3	0 0%	0 0%
Sod. (hypernatremia), Increase to G4	0 0%	1 0.2%
Sod. (hyponatremia), Any Grade Increase	65 28%	151 33.6%
Sod. (hyponatremia), Increase to G1	62 26.7%	134 29.8%
Sod. (hyponatremia), Increase to G2	3 1.3%	11 2.4%
Sod. (hyponatremia), Increase to G3	0 0%	3 0.7%
Sod. (hyponatremia), Increase to G4	0 0%	3 0.7%

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
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)

Outcome Measure Data

Analysis Population Description
Safety DB Population

Arm/Group Title	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase
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).
Measure Participants	232	449
Hemoglobin (anemia), Any Grade Increase	148 63.8%	324 72%
Hemoglobin (anemia), Increase to G1	45 19.4%	91 20.2%
Hemoglobin (anemia), Increase to G2	63 27.2%	128 28.4%
Hemoglobin (anemia), Increase to G3	37 15.9%	98 21.8%
Hemoglobin (anemia), Increase to G4	3 1.3%	7 1.6%
Lym. (lymphocytopenia), Any Grade Increase	123 53%	300 66.7%
Lym. (lymphocytopenia), Increase to G1	16 6.9%	26 5.8%
Lym. (lymphocytopenia), Increase to G2	28 12.1%	50 11.1%
Lym. (lymphocytopenia), Increase to G3	43 18.5%	96 21.3%
Lym. (lymphocytopenia), Increase to G4	36 15.5%	128 28.4%
Tot Neu. (neutropenia), Any Grade Increase	196 84.5%	394 87.6%
Tot Neu. (neutropenia), Increase to G1	32 13.8%	90 20%
Tot Neu. (neutropenia), Increase to G2	39 16.8%	104 23.1%
Tot Neu. (neutropenia), Increase to G3	80 34.5%	129 28.7%
Tot Neu. (neutropenia), Increase to G4	45 19.4%	71 15.8%
WBC (leukocytopenia), Any Grade Increase	187 80.6%	376 83.6%
WBC (leukocytopenia), Increase to G1	51 22%	94 20.9%
WBC (leukocytopenia), Increase to G2	59 25.4%	142 31.6%
WBC (leukocytopenia), Increase to G3	68 29.3%	117 26%
WBC (leukocytopenia), Increase to G4	9 3.9%	23 5.1%

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
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)

Outcome Measure Data

Analysis Population Description
Safety DB Population

Arm/Group Title	Placebo+Antiviral Therapy: DB Phase	Eltrombopag+Antiviral Therapy: DB Phase
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).
Measure Participants	232	449
Unilateral CP, Genotype 2/3	1 0.4%	2 0.4%
Unilateral CP, Non-genotype 2/3	2 0.9%	3 0.7%
Unilateral CP, Missing genotype	0 0%	1 0.2%
Bilateral CP, Genotype 2/3	1 0.4%	6 1.3%
Bilateral CP, Non-genotype 2/3	0 0%	9 2%
Unilateral IP, Genotype 2/3	0 0%	1 0.2%
Unilateral IP, Non-genotype 2/3	2 0.9%	6 1.3%
Bilateral IP, Genotype 2/3	2 0.9%	2 0.4%
Bilateral IP, Non-genotype 2/3	0 0%	8 1.8%

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
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)

Outcome Measure Data

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
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).
Measure Participants	229	447
Antiviral BL, Normal, n=219, 423	149 64.2%	278 61.8%
Antiviral BL, Abnormal - NCS, n=219, 423	53 22.8%	108 24%
Antiviral BL, Abnormal - CS, n=219, 423	17 7.3%	37 8.2%
End of Treatment, Normal, n=198, 384	139 59.9%	251 55.8%
End of Treatment, Abnormal - NCS, n=198, 384	50 21.6%	108 24%
End of Treatment, Abnormal - CS, n=198, 384	9 3.9%	24 5.3%
End of Treatment, Abnormal, n=198, 384	0 0%	1 0.2%
24-week FU, Normal, n=186, 368	120 51.7%	235 52.2%
24-week FU, Abnormal - NCS, n=186, 368	53 22.8%	106 23.6%
24-week FU, Abnormal - CS, n=186, 368	13 5.6%	27 6%
Worst ECG post-BL, Normal, n=229, 447	105 45.3%	188 41.8%
Worst ECG post-BL, Abnormal - NCS, n=229, 447	87 37.5%	186 41.3%
Worst ECG post-BL, Abnormal - CS, n=229, 447	37 15.9%	72 16%
Worst ECG post-BL, Abnormal, n=229, 447	0 0%	1 0.2%

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
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)

Outcome Measure Data

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
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).
Measure Participants	198	383
End of Treatment, CS change from BL, n=198, 383	2 0.9%	5 1.1%
End of Treatment, NCS change from BL, n=198, 383	196 84.5%	377 83.8%
End of Treatment, Not applicable, n=198, 383	0 0%	1 0.2%
24-week FU, CS change from BL, n=186, 369	1 0.4%	8 1.8%
24-week FU, NCS change from BL, n=186, 369	185 79.7%	361 80.2%

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
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)

Outcome Measure Data

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
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).
Measure Participants	231	444
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
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)

Outcome Measure Data

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
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).
Measure Participants	231	443
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
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)

Outcome Measure Data

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
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).
Measure Participants	230	443
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
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)

Outcome Measure Data

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
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).
Measure Participants	228	440
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)

Adverse Events

	Eltrombopag: OL Phase		Placebo+Antiviral Therapy: DB Phase		Eltrombopag+Antiviral Therapy: DB Phase
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
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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Eltrombopag: OL Phase		Placebo+Antiviral Therapy: DB Phase		Eltrombopag+Antiviral Therapy: DB Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/715 (1.1%)		35/232 (15.1%)		89/449 (19.8%)
Blood and lymphatic system disorders
Anemia	0/715 (0%)		1/232 (0.4%)		3/449 (0.7%)
Neutropenia	0/715 (0%)		1/232 (0.4%)		3/449 (0.7%)
Pancytopenia	0/715 (0%)		1/232 (0.4%)		3/449 (0.7%)
Hemolytic Anemia	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Leukopenia	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Thrombocytopenia	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Cardiac disorders
Acute Myocardial Infarction	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Angina Pectoris	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Pericarditis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Pleuropericarditis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Angina Unstable	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Sinus Bradycardia	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Congenital, familial and genetic disorders
Epidermolysis Bullosa	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Ear and labyrinth disorders
Deafness Neurosensory	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Endocrine disorders
Goitre	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Eye disorders
Cataract	0/715 (0%)		2/232 (0.9%)		2/449 (0.4%)
Cataract Nuclear	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Eye Disorder	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Retinal Vein Occlusion	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Visual Acuity Reduced	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Gastrointestinal disorders
Gastric Hemorrhage	1/715 (0.1%)		0/232 (0%)		0/449 (0%)
Hemorrhoids	1/715 (0.1%)		1/232 (0.4%)		0/449 (0%)
Large Intestine Perforation	1/715 (0.1%)		0/232 (0%)		1/449 (0.2%)
Oesophageal Varices Hemorrhage	1/715 (0.1%)		2/232 (0.9%)		7/449 (1.6%)
Ascites	0/715 (0%)		3/232 (1.3%)		4/449 (0.9%)
Upper Gastrointestinal Hemorrhage	0/715 (0%)		0/232 (0%)		4/449 (0.9%)
Colitis	0/715 (0%)		0/232 (0%)		2/449 (0.4%)
Diarrhea	0/715 (0%)		0/232 (0%)		2/449 (0.4%)
Gastric Varices Hemorrhage	0/715 (0%)		0/232 (0%)		2/449 (0.4%)
Gastrointestinal Hemorrhage	0/715 (0%)		0/232 (0%)		2/449 (0.4%)
Abdominal Discomfort	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Abdominal Pain	0/715 (0%)		2/232 (0.9%)		1/449 (0.2%)
Abdominal Pain Upper	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Abdominal Strangulated Hernia	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Gastritis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Hematemesis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Intestinal Obstruction	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Nausea	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Oesophageal Hemorrhage	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Pancreatitis	0/715 (0%)		1/232 (0.4%)		1/449 (0.2%)
Pancreatitis Acute	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Peptic Ulcer	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Periodontitis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Peritonitis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Vomiting	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Abdominal Distension	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Enteritis	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Varices Oesophageal	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
General disorders
Pyrexia	1/715 (0.1%)		0/232 (0%)		3/449 (0.7%)
Chest Pain	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Death	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
General Physical Health Deterioration	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Edema Peripheral	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Multi-organ Failure	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Hepatobiliary disorders
Hepatic Failure	0/715 (0%)		1/232 (0.4%)		7/449 (1.6%)
Cholecystitis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Cholecystitis Acute	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Hepatic Function Abnormal	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Hepatitis Alcoholic	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Hepatorenal Syndrome	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Cholelithiasis	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Hepatic Cirrhosis	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Portal Vein Thrombosis	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Infections and infestations
Pneumonia	1/715 (0.1%)		2/232 (0.9%)		4/449 (0.9%)
Gastroenteritis	0/715 (0%)		1/232 (0.4%)		4/449 (0.9%)
Peritonitis Bacterial	0/715 (0%)		2/232 (0.9%)		3/449 (0.7%)
Urinary Tract Infection	0/715 (0%)		0/232 (0%)		3/449 (0.7%)
Abscess Limb	0/715 (0%)		1/232 (0.4%)		2/449 (0.4%)
Cellulitis	0/715 (0%)		1/232 (0.4%)		2/449 (0.4%)
Septic Shock	0/715 (0%)		0/232 (0%)		2/449 (0.4%)
Bacteremia	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Bacterial Infection	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Bronchitis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Diarrhea Infectious	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Disseminated Tuberculosis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Erysipelas	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Meningitis Cryptococcal	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Prostatic Abscess	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Renal Abscess	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Sepsis	0/715 (0%)		1/232 (0.4%)		1/449 (0.2%)
Subcutaneous Abscess	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Urosepsis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Acinetobacter Bacteremia	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Appendicitis Perforated	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Dacryocystitis	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Pyelonephritis	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Pyelonephritis Acute	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Sinusitis	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Staphylococcal Infection	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Injury, poisoning and procedural complications
Forearm Fracture	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Limb Traumatic Amputation	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Traumatic Lung Injury	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Retinal Injury	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Investigations
Blood Creatinine Increased	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Transaminases Increased	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Metabolism and nutrition disorders
Hyperglycemia	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Musculoskeletal and connective tissue disorders
Bursitis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Fasciitis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Juvenile Arthritis	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic Neoplasm Malignant	2/715 (0.3%)		2/232 (0.9%)		6/449 (1.3%)
Lung Neoplasm Malignant	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Nervous system disorders
Hepatic Encephalopathy	0/715 (0%)		0/232 (0%)		4/449 (0.9%)
Encephalopathy	0/715 (0%)		0/232 (0%)		2/449 (0.4%)
Brain Edema	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Coma	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Convulsion	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Vocal Cord Paralysis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Ruptured Cerebral Aneurysm	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Psychiatric disorders
Mental Status Changes	0/715 (0%)		0/232 (0%)		2/449 (0.4%)
Renal and urinary disorders
Renal Failure	0/715 (0%)		1/232 (0.4%)		2/449 (0.4%)
Renal Failure Acute	0/715 (0%)		0/232 (0%)		2/449 (0.4%)
Cystitis Ulcerative	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Urethral Polyp	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Reproductive system and breast disorders
Dyspnea Exertional	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Prostatitis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/715 (0%)		0/232 (0%)		2/449 (0.4%)
Dyspnea	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Epistaxis	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Respiratory Failure	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Pleurisy	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Social circumstances
Alcohol Use	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Surgical and medical procedures
Portal Shunt	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Vascular disorders
Hypertensive Crisis	1/715 (0.1%)		0/232 (0%)		0/449 (0%)
Bleeding Varicose Vein	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Venous Thrombosis Limb	0/715 (0%)		0/232 (0%)		1/449 (0.2%)
Varicose Vein	0/715 (0%)		1/232 (0.4%)		0/449 (0%)
Other (Not Including Serious) Adverse Events
	Eltrombopag: OL Phase		Placebo+Antiviral Therapy: DB Phase		Eltrombopag+Antiviral Therapy: DB Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/715 (6.9%)		219/232 (94.4%)		424/449 (94.4%)
Blood and lymphatic system disorders
Neutropenia	0/715 (0%)		95/232 (40.9%)		170/449 (37.9%)
Anemia	0/715 (0%)		78/232 (33.6%)		183/449 (40.8%)
Thrombocytopenia	0/715 (0%)		85/232 (36.6%)		69/449 (15.4%)
Leukopenia	0/715 (0%)		39/232 (16.8%)		70/449 (15.6%)
Gastrointestinal disorders
Nausea	0/715 (0%)		30/232 (12.9%)		86/449 (19.2%)
Diarrhea	0/715 (0%)		27/232 (11.6%)		82/449 (18.3%)
Vomiting	0/715 (0%)		17/232 (7.3%)		31/449 (6.9%)
Abdominal Pain	0/715 (0%)		12/232 (5.2%)		33/449 (7.3%)
Dyspepsia	0/715 (0%)		16/232 (6.9%)		27/449 (6%)
Abdominal Pain Upper	0/715 (0%)		11/232 (4.7%)		29/449 (6.5%)
Ascites	0/715 (0%)		7/232 (3%)		32/449 (7.1%)
Constipation	0/715 (0%)		11/232 (4.7%)		28/449 (6.2%)
General disorders
Fatigue	0/715 (0%)		60/232 (25.9%)		139/449 (31%)
Pyrexia	0/715 (0%)		53/232 (22.8%)		139/449 (31%)
Influenza Like Illness	0/715 (0%)		40/232 (17.2%)		70/449 (15.6%)
Asthenia	0/715 (0%)		34/232 (14.7%)		66/449 (14.7%)
Edema Peripheral	0/715 (0%)		20/232 (8.6%)		56/449 (12.5%)
Chills	0/715 (0%)		12/232 (5.2%)		58/449 (12.9%)
Irritability	0/715 (0%)		17/232 (7.3%)		46/449 (10.2%)
Hepatobiliary disorders
Hyperbilirubinemia	0/715 (0%)		5/232 (2.2%)		38/449 (8.5%)
Infections and infestations
Urinary Tract Infection	0/715 (0%)		8/232 (3.4%)		39/449 (8.7%)
Upper Respiratory Tract Infection	0/715 (0%)		12/232 (5.2%)		24/449 (5.3%)
Investigations
Blood Bilirubin Increased	0/715 (0%)		8/232 (3.4%)		44/449 (9.8%)
White Blood Cell Count Decreased	0/715 (0%)		9/232 (3.9%)		32/449 (7.1%)
Hemoglobin Decreased	0/715 (0%)		9/232 (3.9%)		31/449 (6.9%)
Weight Decreased	0/715 (0%)		9/232 (3.9%)		25/449 (5.6%)
Metabolism and nutrition disorders
Decreased Appetite	0/715 (0%)		30/232 (12.9%)		78/449 (17.4%)
Musculoskeletal and connective tissue disorders
Myalgia	0/715 (0%)		26/232 (11.2%)		65/449 (14.5%)
Arthralgia	0/715 (0%)		17/232 (7.3%)		55/449 (12.2%)
Muscle Spasms	0/715 (0%)		15/232 (6.5%)		46/449 (10.2%)
Back Pain	0/715 (0%)		10/232 (4.3%)		26/449 (5.8%)
Nervous system disorders
Headache	49/715 (6.9%)		47/232 (20.3%)		107/449 (23.8%)
Dizziness	0/715 (0%)		24/232 (10.3%)		26/449 (5.8%)
Psychiatric disorders
Insomnia	0/715 (0%)		44/232 (19%)		79/449 (17.6%)
Depression	0/715 (0%)		11/232 (4.7%)		38/449 (8.5%)
Anxiety	0/715 (0%)		13/232 (5.6%)		18/449 (4%)
Respiratory, thoracic and mediastinal disorders
Cough	0/715 (0%)		34/232 (14.7%)		77/449 (17.1%)
Epistaxis	0/715 (0%)		33/232 (14.2%)		30/449 (6.7%)
Dyspnea	0/715 (0%)		15/232 (6.5%)		38/449 (8.5%)
Dyspnea Exertional	0/715 (0%)		16/232 (6.9%)		28/449 (6.2%)
Oropharyngeal Pain	0/715 (0%)		9/232 (3.9%)		30/449 (6.7%)
Skin and subcutaneous tissue disorders
Pruritus	0/715 (0%)		27/232 (11.6%)		68/449 (15.1%)
Rash	0/715 (0%)		24/232 (10.3%)		49/449 (10.9%)
Alopecia	0/715 (0%)		15/232 (6.5%)		50/449 (11.1%)
Dry Skin	0/715 (0%)		14/232 (6%)		31/449 (6.9%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

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

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00516321

Other Study ID Numbers:

TPL103922

First Posted:

Aug 15, 2007

Last Update Posted:

Nov 5, 2013

Last Verified:

Aug 1, 2012

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

Study Details

Study Description

Brief Summary

Study Design

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion criteria:

Subjects with a history of any one of the following:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Certain Agreements

Results Point of Contact