Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01636778
First received: July 5, 2012
Last updated: February 1, 2016
Last verified: September 2015
  Purpose
The purpose of this study is to assess the ability of SB-497115-GR to raise platelet counts in thrombocytopenic patients with hepatitis C virus (HCV) infection (platelet count <80,000 /μL, suggestive of compensated cirrhosis) to a level desirable to initiate antiviral therapy and to assess the ability of SB-497115-GR to maintain platelet counts at a level sufficient to minimise dose reductions of pegylated interferon (Peg-IFN) and ribavirin (RBV) therapy with the expectation that a lower rate of Peg-IFN dose reduction and omission will translate to a higher rate of sustained viral response.

Condition Intervention Phase
Hepatitis C, Chronic
Drug: SB-497115-GR
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Non-randomised, Open Label, Multi-centre Phase II Study to Assess the Efficacy and Safety of SB-497115-GR in Thrombocytopenic Subjects With Chronic Hepatitis C and Compensated Liver Cirrhosis.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants Whose Platelet Count Increased From a Baseline Count of < 80 Gi/L to a Count >=100 Gi/L During Part 1 [ Time Frame: From Baseline up to Week 9 in Part 1 ] [ Designated as safety issue: No ]
    Participants were assessed for a shift from a baseline platelet count of <80 Gi/L to a count >=100 Gi/L during Part 1(up to 9 weeks). Platelet counts were measured by blood draw.

  • Number of Participants Whose Platelet Counts Maintained at >=50 Gi/L During Part 2 [ Time Frame: From Antiviral Baseline to up to Week 48 in Part 2 ] [ Designated as safety issue: No ]

    Participants were assessed for continuously maintaining platelet counts >=50 Gi/L during Part 2.

    Platelet counts were measured by blood draw.



Secondary Outcome Measures:
  • Median Platelet Count at the Indicated Time Points in Part 1 [ Time Frame: Baseline, Week1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 ] [ Designated as safety issue: No ]
    Platelet counts were measured by blood draw

  • Time in Weeks to Achieve Platelet Count >= 100 Gi/L [ Time Frame: From Baseline up to Week 9 in Part 1 ] [ Designated as safety issue: No ]
    Participants were assessed for achieving platelet counts >=100 Gi/L during Part 1. Platelet counts were measured by blood draw.

  • Median Platelet Count at the Indicated Time Points in Part 2 [ Time Frame: Antiviral Baseline, Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2 ] [ Designated as safety issue: No ]
    Platelet counts were measured by blood draw

  • Median Platelet Count at the Indicated Time Points During Follow-up Period After Part 2 [ Time Frame: Follow-up (FU) Baseline, FU Week 4, FU Week 12 and and FU Week 24 after Part 2 ] [ Designated as safety issue: No ]
    Platelet counts were measured by blood draw at specified timepoints.

  • Minimum Platelet Count on Antiviral Therapy [ Time Frame: From Antiviral Baseline to up to Week 48 in Part 2 ] [ Designated as safety issue: No ]

    Participants were assessed for platelet counts during antiviral therapy in Part 2.

    Platelet counts were measured by blood draw.


  • Dose of Eltrombopag That Enabled Initiation of Antiviral Therapy [ Time Frame: From Baseline up to Week 9 in Part 1 ] [ Designated as safety issue: No ]
    Participants received eltrombopag at escalating dosages until a platelet count of >=100 Gi/L was achieved in Part 1. Platelet counts were measured by blood draw.

  • Number of Antiviral Therapy Dose Reductions in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Number of reductions in Part 2 of either Peg-IFN or RBV. Participants were assigned a score equal to the number of times antiviral therapy 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. 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 Peg-IFN and/or RBV.

  • Number of Participants With the Indicated Levels of Peg-IFN Alpha-2a Therapy Dose Reductions in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Participants were assigned a score equal to the number of times their Peg-IFN alpha-2a dose of antiviral therapy 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. 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 Peg-IFN.

  • Number of Participants With the Indicated Levels of Peg-IFN Alpha-2b Therapy Dose Reductions in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Participants were assigned a score equal to the number of times their Peg-IFN alpha-2b dose of antiviral therapy 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. 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 Peg-IFN.

  • Number of Participants With the Indicated Levels of RBV Therapy Dose Reductions in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Participants were assigned a score equal to the number of times their RBV dose of antiviral therapy was reduced (0=no 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. 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 RBV

  • Time to First Dose Reduction of Antiviral Therapy in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Time to first dose reduction was calucated as the time period from the first dose to the first dose reduction.

  • Number of Participants Who Discontinued Antiviral Therapy in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Dosing discontinuation is defined as the occurrence of stopping the medication. Dosing discontinuation of Antviral Therapy was assessed up to 48 weeks in Part 2

  • Number of Participants Who Discontinued Peg-IFN Alpha-2a Therapy in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Dosing discontinuation is defined as the occurrence of stopping the medication. Dosing discontinuation of Peg-IFN alpha-2a therapy was assessed up to 48 weeks in Part 2

  • Number of Participants Who Discontinued Peg-IFN Alpha-2b Therapy in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Dosing discontinuation is defined as the occurrence of stopping the medication. Dosing discontinuation of Peg-IFN alpha-2b therapy was assessed up to 48 weeks in Part 2

  • Number of Participants Achieving Adherence to Antiviral Therapy in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Adherence to antiviral therapy was defined as receiving at least 80% of the prescribed dose (investigator prescribed) of Peg-IFN alfa and at least 80% of the prescribed dose (investigator prescribed) of RBV, for at least 80% of the planned duration

  • Number of Participants Achieving Adherence to Peg-IFN Alpha 2a Antiviral Therapy in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Adherence to antiviral therapy was defined as receiving at least 80% of the prescribed dose (investigator prescribed) of Peg-IFN alfa-2a and at least 80% of the prescribed dose (investigator prescribed) of RBV, for at least 80% of the planned duration.

  • Number of Participants Achieving Adherence to Peg-IFN Alpha-2b Antiviral Therapy in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Adherence to antiviral therapy was defined as receiving at least 80% of the prescribed dose (investigator prescribed) of Peg-IFN alpha-2b and at least 80% of the prescribed dose (investigator prescribed) of RBV, for at least 80% of the planned duration.

  • Number of Participants With Sustained Virologic Response (SVR) in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    Participants with SVR were defined as those with undetectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) at 24 weeks post-completion of treatment period Part 2

  • Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    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 between 4 weeks and 12 weeks after antiviral treatment.

  • Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    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) for Undetectable HCV RNA at the End of Peg-IFN/RBV Treatment in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    ETR is defined as undetectable HCV RNA at the end of Peg-IFN/RBV treatment.

  • Mean Serum HCV RNA at the Indicated Time Points In Part 2 [ Time Frame: Screening, Antviral baseline; Week 4, 12, 24, 36, 48, Withdrawal in Part 2 ] [ Designated as safety issue: No ]
    The HCV is a small, enveloped, single-stranded, positive-sense RNA virus. Log-Transformed HCV RNA was assessed at Screening, Antiviral Baseline, Part 2 week 4, 12, 24, 36, 48 and at withdrawal.

  • Mean Serum HCV RNA at the Indicated Time Points During Follow-up Period After Part 2 [ Time Frame: FU Baseline, FU Week 12 and FU Week 24 after Part 2 ] [ Designated as safety issue: No ]
    The HCV is a small, enveloped, single-stranded, positive-sense RNA virus. Log-Transformed HCV RNA was assessed at FU Baseline, FU Week 12 and FU Week 24 during Follow-up Period after Part 2

  • Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part1 [ Time Frame: From Baseline up to week 9 in Part 1 ] [ Designated as safety issue: No ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect.

  • Number of Participants With Any AE and Any SAE in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 in Part 2 ] [ Designated as safety issue: No ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect.

  • Number of Participants With Any AE and Any SAE During Follow-up Period After Part 2 [ Time Frame: From FU Baseline up to FU Week 24 after Part 2 ] [ Designated as safety issue: No ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect.

  • Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 With Follow-up Period [ Time Frame: Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, and FU Week 24 ] [ Designated as safety issue: No ]
    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 Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 2 [ Time Frame: Baseline; Antiviral Baseline,Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2 ] [ Designated as safety issue: No ]
    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 Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During Follow-up Period After Part 2 [ Time Frame: FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2 ] [ Designated as safety issue: No ]
    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 in Heart Rate at the Indicated Time Points in Part 1 With Follow-up Period [ Time Frame: Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, FU Week 24 ] [ Designated as safety issue: No ]
    The 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 Antiviral Baseline in Heart Rate at the Indicated Time Points in Part 2 [ Time Frame: Antiviral Baseline, Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2 ] [ Designated as safety issue: No ]
    The heart rate was measured in participants at the indicated time points. Mean change from Antiviral Baseline was calculated as the value at the indicated time points minus the value at Antiviral Baseline.

  • Mean Heart Rate at the Indicated Time Points During Follow-up Period After Part 2 [ Time Frame: FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2 ] [ Designated as safety issue: No ]
    The heart rate was measured in participants at the indicated time points.

  • Mean Change From Baseline in Weight at the Indicated Time Points in Part 1 With Follow-up Period [ Time Frame: Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, FU Week 24 ] [ Designated as safety issue: No ]
    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 Weight at the Indicated Time Points in Part 2 [ Time Frame: Baseline; Antiviral Baseline, Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2 ] [ Designated as safety issue: No ]
    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 Weight at the Indicated Time Points During Follow-up Period After Part 2 [ Time Frame: FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2 ] [ Designated as safety issue: No ]
    The weight of participants was recorded at the indicated time points.

  • Mean Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 With Follow-up Period [ Time Frame: Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, FU Week 24 ] [ Designated as safety issue: No ]
    The Body temperature 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 Temperature at the Indicated Time Points in Part 2 [ Time Frame: Baseline; Antiviral Baseline,Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2 ] [ Designated as safety issue: No ]
    The Body temperature 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 Body Temperature at the Indicated Time Points During Follow-up Period After Part 2 [ Time Frame: FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2 ] [ Designated as safety issue: No ]
    The Body temperature of participants was recorded at the indicated time points..

  • Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points in Part 1 With Follow-up Periodc [ Time Frame: Baseline; Week 1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1 and FU Week 4, FU Week 12, FU Week 24 ] [ Designated as safety issue: No ]
    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

  • Mean Change From Baseline in BMI at the Indicated Time Points in Part 2 [ Time Frame: Baseline; Antiviral Baseline,Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2 ] [ Designated as safety issue: No ]
    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

  • Mean BMI at the Indicated Time Points During Follow-up Period After Part 2 [ Time Frame: FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2 ] [ Designated as safety issue: No ]
    The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared.

  • Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per Division of Acquired Immunodeficiency Syndrome (DAIDS) in Part 1 [ Time Frame: From Baseline up to Week 9 ] [ Designated as safety issue: No ]
    Blood samples for the assessment of clinical chemistry parameters were taken at intervals in Part 1. Clinical chemistry parameters included albumin, alkaline phosphatase (ALP), ALT, aspartate amino transferase (AST), total bilirubin, calcium, creatinine, potassium, sodium, and uric acid. Per DAIDS toxicity table, the grade ranges for each parameter are as follows: Grade (G) 0=none, 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

  • Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per DAIDS in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 ] [ Designated as safety issue: No ]
    Blood samples for the assessment of clinical chemistry parameters were taken at intervals in Part 2. Clinical chemistry parameters included albumin, ALP, ALT, AST, total bilirubin, calcium, creatinine, potassium, sodium, and uric acid. Per DAIDS toxicity table, the grade ranges for each parameter are as follows: Grade (G) 0=none, 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

  • Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per DAIDS During Follow-up Period After Part 2 [ Time Frame: From FU Week 4 to FU Week 24 ] [ Designated as safety issue: No ]
    Blood samples for the assessment of clinical chemistry parameters were taken at intervals in Part 2. Clinical chemistry parameters included albumin, ALP, ALT, AST, total bilirubin, calcium, creatinine, potassium, sodium, and uric acid. Per DAIDS toxicity table, the grade ranges for each parameter are as follows: Grade (G) 0=none, 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 Per DAIDS in Part 1 [ Time Frame: From Baseline up to Week 9 ] [ Designated as safety issue: No ]
    Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL in Part 1 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 With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters Per DAIDS in Part 2 [ Time Frame: From Antiviral Baseline up to Week 48 ] [ Designated as safety issue: No ]
    Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL in Part 2 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 With the Indicated Shifts From BL in Severity Grades for Hematology Parameters Per DAIDS During Follow-up Period After Part 2 [ Time Frame: From FU Week 4 to FU Week 24 ] [ Designated as safety issue: No ]
    Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL in Part 2 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 With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part1 With Follow Up Period [ Time Frame: Screening, Baseline, Week 1, 2, 3, 4, 7, 8, Withdrawal, FU Week 24 ] [ Designated as safety issue: No ]
    Urinalysis parameters included: urine bilirubin (UB), urine occult blood (UOB), urine glucose (UG), urine ketones (UK), pH, urine protein (UP), urine specific gravity (USG) and urine urobilinogen (UU). The dipstick test gives results in a semi-quantitative manner. UB was categorized as (-), negative (Neg). UOB was categorised as 1+, 2+, 3+, (-), Neg, trace. UG results were categorized as (-), 0.5, Neg. UK parameters were categorized as as (-), Neg. pH results were in the range of pH from 5-8.5 in increments of 0.5. UP was categorized as 1+, (-), Neg, trace. UU was categorized as 1+, 0.1, 1, 2, 4, Neg, trace, normal. USG results were in the range from 1.000-1.030 in increments of 0.001.

  • Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part 2 [ Time Frame: Antiviral Baseline,Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal ] [ Designated as safety issue: No ]
    Urinalysis parameters included: UB, UOB, UG, UK, pH, UP, USG and UU. The dipstick test gives results in a semi-quantitative manner. UB was categorized as (-), negative (Neg). UOB was categorised as 1+, 2+, 3+, (-), Neg, trace. UG results were categorized as 1+, (-), 0.5, Neg. UK parameters were categorized as as (-), Neg. pH results were in the range of pH from 5-8.5 in increments of 0.5. UP was categorized as (-), Neg, trace. UU was categorized as 1+, 0.1, 1, 2, 4, Neg, trace, normal. USG results were in the range from 1.000-1.030 in increments of 0.001.

  • Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points During Follow-up Period After Part 2 [ Time Frame: FU Baseline and FU Week 24 ] [ Designated as safety issue: No ]
    Urinalysis parameters included: UB, UOB, UG, UK, pH, UP, USG and UU. The dipstick test gives results in a semi-quantitative manner. UB was categorized as (-), negative (Neg). UOB was categorised as 1+, 2+, 3+, (-), Neg, trace. UG results were categorized as 1+, (-), 0.5, Neg. UK parameters were categorized as as (-), Neg. pH results were in the range of pH from 5-8.5 in increments of 0.5. UP was categorized as (-), Neg, trace. UU was categorized as 1+, 0.1, 1, 2, 4, Neg, trace, normal. USG results were in the range from 1.000-1.030 in increments of 0.001.

  • Number of Participants Assessed as Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at the Indicated Time Points [ Time Frame: Screening, Antiviral Baseline, Week 12, 24, 36, 48, Withdrawal ] [ Designated as safety issue: No ]
    The number of participants with an ECG status of normal, abnormal, CS, or NCS, as determined by the Investigator, was reported. Normal= all ECG parameters within accepted normal ranges. Abnormal= ECG findings 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 Assessed as Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) During Follow-up After Part 2 [ Time Frame: FU Baseline and FU Week 24 ] [ Designated as safety issue: No ]
    The number of participants with an ECG status of normal, abnormal, CS, or NCS, as determined by the Investigator, was reported. Normal= all ECG parameters within accepted normal ranges. Abnormal= ECG findings 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 Abdominal Ultrasound With Doppler at the Indicated Time Points [ Time Frame: Baseline; Week 24, Week 48, Withdrawal/Completion ] [ Designated as safety issue: No ]
    Abdominal ultrasound with doppler were taken at Baseline, Week 24, Week 48, withdrawal (WD)/completion (comp). Questions were asked to assess masses suspicious for hepatocellular carcinoma (HCC), ascites, portal vein thrombosis detected, possiblility to measure spleen breadth, and other clinically significant findings (OCSF).

  • Number of Participants With Abdominal Ultrasound With Doppler During Follow-up Period After Part 2 [ Time Frame: FU Week 24 ] [ Designated as safety issue: No ]
    Abdominal ultrasound with doppler were taken during Follow-up Period after Part 2 at FU Week 24. Questions were asked to assess masses suspicious for hepatocellular carcinoma (HCC), ascites, portal vein thrombosis detected, possiblility to measure spleen breadth, and other clinically significant findings (OCSF).

  • Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler in the Study [ Time Frame: Baseline; Week 24, Week 48, Withdrawal/Completion ] [ Designated as safety issue: No ]
    Abdominal ultrasound with doppler were taken at Baseline, Week 24, Week 48, WD/comp. Questions were asked to assess masses suspicious for HCC, ascites, portal vein thrombosis detected, possiblility to measure spleen breadth, and OCSF. Spleen measurements included spleen length and spleen width (breadth).

  • Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler During Follow-up Period After Part 2 [ Time Frame: FU Week 24 ] [ Designated as safety issue: No ]
    Abdominal ultrasound with doppler were taken during Follow-up Period after Part 2 at FU Week 24. Questions were asked to assess masses suspicious for HCC, ascites, portal vein thrombosis detected, possiblility to measure spleen breadth, and OCSF. Spleen measurements included spleen length and spleen width (breadth).


Enrollment: 45
Study Start Date: July 2012
Study Completion Date: November 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SB-497115-GR
investigational product for thrombocytopenia
Drug: SB-497115-GR
TPO receptor agonist to increase platelet count

  Eligibility

Ages Eligible for Study:   20 Years to 74 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subject is able to understand and comply with protocol requirements and instructions and is likely to complete the study as planned, as well as provided a written consent.

  • A subject age between ≥20 and <75 years at time of informed consent.
  • A subject who applies to one of the following:

Female subject with non-childbearing potential [i.e., physiologically incapable of becoming pregnant, who: has had a hysterectomy, or had a bilateral oophorectomy (ovariectomy), or had a bilateral tubal ligation, or is post-menopausal for greater than one year].

Female subject with childbearing potential, has a negative urine or serum pregnancy test at screening and within the 24-hour period prior to the first dose of SB-497115-GR, and completely abstains from intercourse or agree to use two of the following acceptable methods of contraception for 14 days before exposure to SB-497115-GR, throughout the clinical trial, and for 24 weeks after completion or premature discontinuation from the study.

Intrauterine device or intrauterine system that meets the effectiveness criteria as stated in the product label.

Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject.

Double-barrier contraception (condom with spermicidal jelly, or diaphragm with spermicide).

Male subject with childbearing potential partner completely abstains from intercourse or agree to use condom and diaphragm with spermicide.

  • Subjects who were diagnosed as hepatitis C or compensated liver cirrhosis (Child-Pugh class A) without hepatic encephalopathy, or ascites. If there is a clear cirrhosis, treatment should be given with care as there is a potential of progressing to liver failure.
  • Subjects who, in the opinion of the investigator, are appropriate candidates for Peg-IFN and RBV combination therapy for 48 weeks.
  • HCV positive by TaqMan test at screening.
  • Subject who fulfil all the organ functions below.

Items Values Platelet <80,000 /μL Haemoglobin ≥12.0 g/dL* Absolute neutrophil count (ANC) ≥1500 /μL* Creatinine clearance >50 mL/minute Total bilirubin <2.0 mg/dL Albumin >3.0 g/dL Prothrombin time >60%

*If the investigators consider the values are sufficient to give Peg-IFN/RBV, then a subject can be enrolled upon consulting the Medical Monitor.

Exclusion Criteria:

  • Subject who relapsed or did not respond after 48 weeks of Peg-IFN/RBV therapy had been given with sufficient dose previously.
  • Subject with history of IFN (including Peg-IFN) therapy or Peg-IFN/RBV therapy, but could not been treated with optimal Peg-IFN/RBV therapy due to the reasons other than thrombocytopenia.
  • Subject who received IFN therapy (including Peg-IFN), antiviral therapy (excluding oseltamivir phosphate, etc.), immuno-modulatory treatment, radiotherapy or phlebotomy within 3 months (90 days) prior to the first dose of SB-497115-GR.
  • Treatment with an investigational drug within 30 days prior to the first dose of SB-497115-GR or 5 half-lives of that investigational drug (whichever is longer).
  • Subject with decompensated liver disease.
  • Chronic liver disease other than chronic hepatitis C (e.g., autoimmune hepatitis, alcohol-induced hepatitis, drug-induced hepatitis, etc.).
  • Subject with idiopathic thrombocytopenic purpura or active autoimmune disease.
  • Subject who have had a malignancy diagnosed and/or treated within the past 5 years.
  • Subjects who require endoscopic treatment for varices or documented history of clinically significant bleeding from oesophageal or gastric varices.
  • Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin.
  • Subject with serious cardiac, cerebrovascular, chronic pulmonary disease or interstitial lung disease, or documented history of any of these diseases.
  • Pre-existing cardiac disease (congestive heart failure in New York Heart Association Grade III/IV), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTcF >450 msec or if with bundle brunch block, QTcF >480 msec.
  • Subject with depression, psychiatric disorder requiring treatment or suicidal ideation or suicide attempt history, or history of these.
  • Subject with uncontrolled hypertension (≥160 mmHg systolic or ≥100 mmHg diastolic).
  • Subject with diabetes mellitus that can not be controlled by treatment.
  • Thyroid dysfunction not adequately controlled.
  • Subjects with haemoglobinopathies.
  • History or current condition of seizure disorder.
  • Subject who was positive for Human Immunodeficiency Virus (HIV) antibody or Hepatitis B Virus (HBV) antigen.
  • Subject with arterial or venous thrombosis history or evidence of portal vein thrombosis on abdominal imaging (e.g., by computerized tomography or magnetic resonance imaging) within 3 months.
  • History of alcohol/drug abuse or dependence.
  • History of platelet clumping that prevents reliable measurement of platelet counts.
  • Subjects planning to have cataract surgery.
  • History of major organ transplantation.
  • Known hypersensitivity to SB-497115-GR ingredients, IFN (including Peg-IFN), nucleoside analogues or biological agents (i.e., vaccines).
  • Pregnant or nursing women or a male subject with pregnant partner.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01636778

Locations
Japan
GSK Investigational Site
Aichi, Japan, 467-8602
GSK Investigational Site
Fukui, Japan, 918-8503
GSK Investigational Site
Fukuoka, Japan, 803-8505
GSK Investigational Site
Fukuoka, Japan, 830-0011
GSK Investigational Site
Gunma, Japan, 370-0829
GSK Investigational Site
Hyogo, Japan, 663-8501
GSK Investigational Site
Ibaraki, Japan, 317-0077
GSK Investigational Site
Kagawa, Japan, 760-0017
GSK Investigational Site
Kagawa, Japan, 760-8557
GSK Investigational Site
Kagoshima, Japan, 899-5112
GSK Investigational Site
Kanagawa, Japan, 213-8587
GSK Investigational Site
Nagasaki, Japan, 856-8562
GSK Investigational Site
Oita, Japan, 879-5593
GSK Investigational Site
Osaka, Japan, 540-0006
GSK Investigational Site
Tokyo, Japan, 105-8470
GSK Investigational Site
Wakayama, Japan, 646-8558
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01636778     History of Changes
Other Study ID Numbers: 116101 
Study First Received: July 5, 2012
Results First Received: January 22, 2015
Last Updated: February 1, 2016
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
Thrombocytopenia
Hepatitis C, chronic

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic

ClinicalTrials.gov processed this record on August 29, 2016