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

Hepatitis C, Chronic Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01636778
• Other study ID #: 116101
• Status: Completed
• Phase: Phase 2
• First received: July 5, 2012
• Last updated: February 1, 2016
• Start date: July 2012
• Est. completion date: November 2014

Study information

• Verified date: September 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: November 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 74 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• SB-497115-GR
TPO receptor agonist to increase platelet count

Locations

Country	Name	City	State
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Fukui
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Nagasaki
Japan	GSK Investigational Site	Oita
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Wakayama

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Whose Platelet Count Increased From a Baseline Count of < 80 Gi/L to a Count >=100 Gi/L During Part 1	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.	From Baseline up to Week 9 in Part 1	No
Primary	Number of Participants Whose Platelet Counts Maintained at >=50 Gi/L During Part 2	Participants were assessed for continuously maintaining platelet counts >=50 Gi/L during Part 2.; Platelet counts were measured by blood draw.	From Antiviral Baseline to up to Week 48 in Part 2	No
Secondary	Median Platelet Count at the Indicated Time Points in Part 1	Platelet counts were measured by blood draw	Baseline, Week1, 2, 3, 4, 5, 6, 7, 8, 9, Withdrawal in Part 1	No
Secondary	Time in Weeks to Achieve Platelet Count >= 100 Gi/L	Participants were assessed for achieving platelet counts >=100 Gi/L during Part 1. Platelet counts were measured by blood draw.	From Baseline up to Week 9 in Part 1	No
Secondary	Median Platelet Count at the Indicated Time Points in Part 2	Platelet counts were measured by blood draw	Antiviral Baseline, Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2	No
Secondary	Median Platelet Count at the Indicated Time Points During Follow-up Period After Part 2	Platelet counts were measured by blood draw at specified timepoints.	Follow-up (FU) Baseline, FU Week 4, FU Week 12 and and FU Week 24 after Part 2	No
Secondary	Minimum Platelet Count on Antiviral Therapy	Participants were assessed for platelet counts during antiviral therapy in Part 2.; Platelet counts were measured by blood draw.	From Antiviral Baseline to up to Week 48 in Part 2	No
Secondary	Dose of Eltrombopag That Enabled Initiation of Antiviral Therapy	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.	From Baseline up to Week 9 in Part 1	No
Secondary	Number of Antiviral Therapy Dose Reductions in Part 2	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.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants With the Indicated Levels of Peg-IFN Alpha-2a Therapy Dose Reductions in Part 2	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.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants With the Indicated Levels of Peg-IFN Alpha-2b Therapy Dose Reductions in Part 2	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.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants With the Indicated Levels of RBV Therapy Dose Reductions in Part 2	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	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Time to First Dose Reduction of Antiviral Therapy in Part 2	Time to first dose reduction was calucated as the time period from the first dose to the first dose reduction.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants Who Discontinued Antiviral Therapy in Part 2	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	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants Who Discontinued Peg-IFN Alpha-2a Therapy in Part 2	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	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants Who Discontinued Peg-IFN Alpha-2b Therapy in Part 2	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	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants Achieving Adherence to Antiviral Therapy in Part 2	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	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants Achieving Adherence to Peg-IFN Alpha 2a Antiviral Therapy in Part 2	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.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants Achieving Adherence to Peg-IFN Alpha-2b Antiviral Therapy in Part 2	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.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants With Sustained Virologic Response (SVR) in Part 2	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	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) in Part 2	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.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) in Part 2	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.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants With End of Treatment Response (ETR) for Undetectable HCV RNA at the End of Peg-IFN/RBV Treatment in Part 2	ETR is defined as undetectable HCV RNA at the end of Peg-IFN/RBV treatment.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Mean Serum HCV RNA at the Indicated Time Points In Part 2	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.	Screening, Antviral baseline; Week 4, 12, 24, 36, 48, Withdrawal in Part 2	No
Secondary	Mean Serum HCV RNA at the Indicated Time Points During Follow-up Period After Part 2	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	FU Baseline, FU Week 12 and FU Week 24 after Part 2	No
Secondary	Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part1	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.	From Baseline up to week 9 in Part 1	No
Secondary	Number of Participants With Any AE and Any SAE in Part 2	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.	From Antiviral Baseline up to Week 48 in Part 2	No
Secondary	Number of Participants With Any AE and Any SAE During Follow-up Period After Part 2	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.	From FU Baseline up to FU Week 24 after Part 2	No
Secondary	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	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	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	No
Secondary	Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 2	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	Baseline; Antiviral Baseline,Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2	No
Secondary	Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During Follow-up Period After Part 2	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.	FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2	No
Secondary	Mean Change From Baseline in Heart Rate at the Indicated Time Points in Part 1 With Follow-up Period	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.	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	No
Secondary	Mean Change From Antiviral Baseline in Heart Rate at the Indicated Time Points in Part 2	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.	Antiviral Baseline, Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2	No
Secondary	Mean Heart Rate at the Indicated Time Points During Follow-up Period After Part 2	The heart rate was measured in participants at the indicated time points.	FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2	No
Secondary	Mean Change From Baseline in Weight at the Indicated Time Points in Part 1 With Follow-up Period	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.	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	No
Secondary	Mean Change From Baseline in Weight at the Indicated Time Points in Part 2	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.	Baseline; Antiviral Baseline, Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2	No
Secondary	Mean Weight at the Indicated Time Points During Follow-up Period After Part 2	The weight of participants was recorded at the indicated time points.	FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2	No
Secondary	Mean Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 With Follow-up Period	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.	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	No
Secondary	Mean Change From Baseline in Body Temperature at the Indicated Time Points in Part 2	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	Baseline; Antiviral Baseline,Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2	No
Secondary	Mean Body Temperature at the Indicated Time Points During Follow-up Period After Part 2	The Body temperature of participants was recorded at the indicated time points..	FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2	No
Secondary	Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points in Part 1 With Follow-up Periodc	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	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	No
Secondary	Mean Change From Baseline in BMI at the Indicated Time Points in Part 2	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	Baseline; Antiviral Baseline,Week 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal in Part 2	No
Secondary	Mean BMI at the Indicated Time Points During Follow-up Period After Part 2	The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared.	FU Baseline, FU Week 4, FU Week 12 and FU Week 24 after Part 2	No
Secondary	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	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.	From Baseline up to Week 9	No
Secondary	Number of Participants With the Indicated Shift From Baseline in Severity Grades for Clinical Chemistry Parameters Per DAIDS in Part 2	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.	From Antiviral Baseline up to Week 48	No
Secondary	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	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.	From FU Week 4 to FU Week 24	No
Secondary	Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters Per DAIDS in Part 1	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.	From Baseline up to Week 9	No
Secondary	Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters Per DAIDS in Part 2	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.	From Antiviral Baseline up to Week 48	No
Secondary	Number of Participants With the Indicated Shifts From BL in Severity Grades for Hematology Parameters Per DAIDS During Follow-up Period After Part 2	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.	From FU Week 4 to FU Week 24	No
Secondary	Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part1 With Follow Up Period	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.	Screening, Baseline, Week 1, 2, 3, 4, 7, 8, Withdrawal, FU Week 24	No
Secondary	Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points in Part 2	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.	Antiviral Baseline,Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, Withdrawal	No
Secondary	Number of Participants With the Indicated Urinalysis Parameters Tested by Dipstick at the Indicated Time Points During Follow-up Period After Part 2	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.	FU Baseline and FU Week 24	No
Secondary	Number of Participants Assessed as Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at the Indicated Time Points	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.	Screening, Antiviral Baseline, Week 12, 24, 36, 48, Withdrawal	No
Secondary	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	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.	FU Baseline and FU Week 24	No
Secondary	Number of Participants With Abdominal Ultrasound With Doppler at the Indicated Time Points	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).	Baseline; Week 24, Week 48, Withdrawal/Completion	No
Secondary	Number of Participants With Abdominal Ultrasound With Doppler During Follow-up Period After Part 2	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).	FU Week 24	No
Secondary	Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler in the Study	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).	Baseline; Week 24, Week 48, Withdrawal/Completion	No
Secondary	Spleen Measurements as Assessed by Abdominal Ultrasound With Doppler During Follow-up Period After Part 2	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).	FU Week 24	No