Hepatitis C, Chronic
Conditions
Keywords
chronic hepatitis C, NS5A inhibitor, ribavirin, pegylated interferon, GSK2336805
Brief summary
GSK2336805 is a hepatitis C virus (HCV) NS5A inhibitor being developed for the treatment of chronic hepatitis C (CHC). This study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with chronic hepatitis C (CHC).
Detailed description
HCV infection is a major public health problem globally and a leading cause of chronic liver disease. New medications are needed that are better tolerated and offer a greater chance of achieving sustained viral clearance compared to currently available therapy. GSK2336805 is a HCV NS5A inhibitor being developed for the treatment of subjects with CHC. This Phase II, double blind, randomized, placebo-controlled study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with CHC. Subjects will be randomly allocated on a 2:1 basis to GSK2336805 or matching placebo and will be stratified by IL28B status and HCV viral genotype (genotype 1 or 4). The study consists of 2 parts. In Part 1, GSK2336805 or matching placebo will be given as single-dose monotherapy (Day 1). In Part 2, GSK2336805 or matching placebo will be co-administered with peginterferon alfa-2a and ribavirin through 4 weeks of treatment (Days 2 to 28). After completion of Part 2, GSK2336805/matching placebo will be discontinued and subjects will be offered continued standard-of-care anti-HCV therapy.
Interventions
DRUGGSK2336805
Active Investigational Drug
DRUGPegylated interferon alfa-2a
Standard of Care drug
DRUGRibavirin
Standard of Care drug
DRUGGSK2336805 Matching Placebo
Placebo of Investigational Drug
Sponsors
PPD Development, LP
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Documented chronic genotype 1 or genotype 4 HCV infection * Naïve to all HCV antiviral treatment(s) * Agree to IL28B genotyping * A body mass index \>18 kg/m2 but not exceeding 36 kg/m2 * Liver biopsy obtained within 3 years (36 calendar months) prior to the Day 1 visit, with a fibrosis classification of non-cirrhotic. If no recent (\<36 months) liver biopsy is available, a study qualifying biopsy must be performed prior to Baseline (Day 1) * All fertile males and females must use two forms of effective contraception between them during treatment and during the 24 weeks after treatment ends * Otherwise healthy as determined by the medical history, physical examination, ECG findings, and clinical laboratory measurements performed at Screening Key
Exclusion criteria
* Positive test at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody * History of any other clinically significant chronic liver disease * History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease * Positive results on urine screen for drugs of abuse test at Screening (unless used as medical treatment, e.g., with a prescription) * History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) * Screening ECG corrected QT interval value greater than 450 ms and/or clinically significant ECG findings * A personal or family history of Torsade de Pointes findings * Pregnant or nursing women * Males with a female partner who is pregnant * Abnormal hematological and biochemical parameters as specified in the protocol * History of major organ transplantation with an existing functional graft * Thyroid dysfunction not adequately controlled * Subjects with a history of suicide attempt or hospitalization for depression in the past 5 years and/or any current (within 6 months) severe or poorly controlled psychiatric disorder * History or current evidence of immunologic disorder; pulmonary, cardiac, or pulmonary disease; seizure disorder; cancer or history of malignancy that in the opinion of the investigator makes the subject unsuitable for the study * Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to first dose administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis | Day 28 | RVR was defined as the proportion of participants below the assay lower limit of detection (LOD) \<18 International units per milliliter (IU/mL) for Hepatitis C virus (HCV) ribonucleic acid (RNA) after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure . Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants. |
| Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses) | Day 28 | RVR was defined as the proportion of participants LOD \<18 IU/mL for HCV RNA after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure. Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants. The primary and supportive analysis differs from the nominal analysis as supportive analysis is assessed at Day 28 ± 2 (2 days visit window) whereas, the nominal analysis was assessed at Day 28. |
| Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis | Day 28 | The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed by nominal analysis was reported. |
| Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses | Day 28 | The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed was reported. |
| Number of Participants With HCV Genotype 1 With Virologic Response | Day 7, 14 and 21 | Serum for determination of HCV genotype was collected at the screening visit. Genotype was determined by the VERSANT HCV genotype 2.0 Assay (LiPA). Number of participants with HCV genotype 1 were reported. |
| Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | Day 1 (Baseline [Pre-dose], 1, 2, 4, 6, and 8 and 24 h) | Blood samples for determination of HCV RNA levels were collected at immediately prior to and 1, 2, 4, 6, and 8 and 24 h after the first dose in Part 1 (Day 1). Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value. Virus RNA levels reported as \<43 are undetectable levels. If the result for HCV RNA (IU/ML) was \<43, then change from Baseline was calculated using 42, and the change from Baseline on the log scale was calculated using log (42). |
| Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period | Up to Day 28 | AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. |
| Change From Baseline in QTcF Interval at Day 2 and 28 | Baseline (Day 1, Pre-dose ), Day 2 and Day 28 | Single 12-lead electrocardiogram (ECG) was obtained. The standard ECG criteria of potential clinical importance were 1) absolute QTc Interval, \> 450 milliseconds (msec), 2) absolute PR Interval, \<110 msec, 3) absolute QRS Interval, \< 75 msec and 4) increase from baseline in QTc \> 60 msec. QTc Interval was calculated using Frederica correction formula: QTcF = QT / (RR)\^1/3. Change from Baseline was calculated by subtracting the Baseline assessment value from post Baseline visit value. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. The change from Baseline in QTc Interval at Day 2 and 28 were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Area Under the Concentration-time Curve (AUC[0-24]), AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK2336805, at Day 1 | 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2) | AUC values were determined using the linear-up, log-down trapezoidal rule. The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were below quantification limit (BLQ) before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters. |
| Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1 | 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2) | The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters |
| Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Baseline (Day 1) to Day 28 | Laboratory abnormalities were graded according to the modified division of AIDS ( DAIDS）version 1.0. Shift from Baseline to worst post baseline toxicity grade (where applicable) were presented for Day 1 to Day 28. The toxicity Grades were, Grade 1: mild (no or minimal interference with usual social & functional activities); Grade 2: moderate (greater than minimal interference with usual social and functional activities); Grade 3: severe (inability to perform usual social and functional activities); Grade 4: potentially life threatening (inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death). Hematology parameters were red blood cell, hemoglobin, hematocrit, platelet white blood cell count with differential leukocyte count, mean corpuscular volume, prothrombin time and international normalized ratio. |
| Mean Apparent Clearance (CL/F) of GSK2336805 | 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1) | The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters |
| Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | 0 (pre-dose), 0 to 2 h, > 2 h up to 4 h, > 4 h up to 6 h, or > 6 h up to 10 h on Days 7, 14, 21 and 28 | The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters. |
| Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1 | 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1) | The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by non-compartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters. |
| Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Baseline (Day 1) and 28 | Abnormalities were graded according to the modified DAIDS version 1.0. Shift from Baseline to worst post Baseline toxicity grade were presented for Day 1 to Day 28. The toxicity Grades were, Grade 1: mild (no or minimal interference with usual social & functional activities); Grade 2: moderate (greater than minimal interference with usual social and functional activities); Grade 3: severe (inability to perform usual social and functional activities); Grade 4: potentially life threatening (inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death). Clinical chemistry parameters were alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatine phosphokinase, total CO2, chloride, creatinine, glucose, sodium, phosphate, potassium, total albumin, total bilirubin, and direct bilirubin. Only participants with change in toxicity grades are reported. |
| Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Day 14, 28, Follow-up (Day 42) | The urinalysis parameters analyzed were Leukocyte esterase, bilirubin, occult blood, glucose, ketones, nitrite, pH, specific gravity and dipstick assessments. Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important urinalysis findings at specified visit were reported. Visits where no abnormal values were observed not reported. |
| Number of Participants With Vital Signs of Potential Clinical Concern | Up to 42 days | The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (\<85 and \>160 millimeter of mercury \[mmHg\]), diastolic blood pressure (\<45 and \>100 mmHg) and heart rate (\<40 and \>110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported. |
| Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28 | Baseline (Day 1, pre-dose), Day 2 (24 h, Post-dose) and Day 28 | Blood samples for determination of HCV RNA levels were collected from screening, immediately prior to and 1, 2, 4, 6, and 8 h after the first dose in Part 1 (Day 1), during Part 2 on Days 2 (24 h after the Day 1 dose), 7, 14, 21, and 28, and at the post-treatment follow-up visit on Day 42. All viral load samples, with the exception of the one taken during the screening visit, were taken in duplicate. The actual time and date of each sample collection will be recorded. Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. |
| Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28 | Baseline (Day 1, Pre -dose ) and Day 2 (24 h, post-dose), Day 28 | Blood samples for determination of HCV RNA levels were collected from screening, immediately prior to and 1, 2, 4, 6, and 8 h after the first dose in Part 1 (Day 1), during Part 2 on Days 2 (24 h after the Day 1 dose), 7, 14, 21, and 28, and at the post-treatment follow-up visit on Day 42. All viral load samples, with the exception of the one taken during the screening visit, were taken in duplicate. The actual time and date of each sample collection will be recorded. Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. |
| Change From Baseline in Serum Alanine Aminotransferase Levels | Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 | Blood samples were collected at Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 for determination of serum alanine aminotransferase levels. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value. |
| Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 | Blood samples were collected at Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 for determination of serum alanine aminotransferase levels. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at 5 sites in the United States. The first participant was randomly assigned to study drug on 20 July 2011 and the last participant completed the study on 05 December 2011.
Pre-assignment details
A total of 16 participants were enrolled and randomly assigned to study medication. One participant with genotype-1 who was randomly assigned to study medication withdrew before receiving the first dose and was not included in any of the analysis populations.
Participants by arm
| Arm | Count |
|---|---|
| GSK2336805 60 mg + PEG + RIBA Eligible participants received GSK2336805 60 mg orally once daily on Day 1 (Part A) of the study. Part 2 of the study then proceeded without interruption with the co-administration of GSK2336805 60 mg once daily with PEG 180 mcg per week as SC and RIBA 1000 mg (if \<75 kg) or 1200 mg (if \<75 kg) orally in 2 divided doses with food (morning and evening) (2 or three 200 mg tablets in the morning and three 200 mg tablets in the evening) through 4 weeks of treatment from Day 2 through Day 28 of the study. | 11 |
| Placebo + PEG + RIBA Eligible participants received matching placebo orally once daily on Day 1 (Part A) of the study. Part 2 of the study then proceeded without interruption with the co-administration of matching placebo once daily with PEG 180 mcg per week as SC and RIBA 1000 mg (if \<75 kg) or 1200 mg (if \<75 kg) orally in 2 divided doses with food (morning and evening) (2 or three 200 mg tablets in the morning and three 200 mg tablets in the evening) through 4 weeks of treatment from Day 2 through Day 28 of the study. | 4 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Combined With PEG and RIBA (Day 2 to 28) | Adverse Event | 2 | 0 |
| Monotherapy (Day 1) | Participant Dropped-out at Day 1 visit | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo + PEG + RIBA | Total | GSK2336805 60 mg + PEG + RIBA |
|---|---|---|---|
| Age, Customized 31 to 67 years | 4 Particiapnts | 15 Particiapnts | 11 Particiapnts |
| Race/Ethnicity, Customized African American/African Heritage | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 2 Participants | 10 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 14 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 4 |
| other Total, other adverse events | 11 / 11 | 4 / 4 |
| serious Total, serious adverse events | 0 / 11 | 0 / 4 |
Outcome results
Primary
Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale
Blood samples for determination of HCV RNA levels were collected at immediately prior to and 1, 2, 4, 6, and 8 and 24 h after the first dose in Part 1 (Day 1). Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value. Virus RNA levels reported as \<43 are undetectable levels. If the result for HCV RNA (IU/ML) was \<43, then change from Baseline was calculated using 42, and the change from Baseline on the log scale was calculated using log (42).
Time frame: Day 1 (Baseline [Pre-dose], 1, 2, 4, 6, and 8 and 24 h)
Population: Intent-to-Treat Exposed population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 1 h post-dose | 0.02 Log IU/mL | Standard Deviation 0.31 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 2 h post-dose | -0.03 Log IU/mL | Standard Deviation 0.21 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 4 h post-dose | -0.70 Log IU/mL | Standard Deviation 0.42 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 6 h post-dose | -1.37 Log IU/mL | Standard Deviation 0.63 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 8 h post-dose | -1.83 Log IU/mL | Standard Deviation 0.81 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 24 h post-dose | -2.38 Log IU/mL | Standard Deviation 1.15 |
| Placebo + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 8 h post-dose | 0.07 Log IU/mL | Standard Deviation 0.11 |
| Placebo + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 1 h post-dose | -0.01 Log IU/mL | Standard Deviation 0.06 |
| Placebo + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 6 h post-dose | 0.08 Log IU/mL | Standard Deviation 0.15 |
| Placebo + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 2 h post-dose | -0.00 Log IU/mL | Standard Deviation 0.07 |
| Placebo + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 24 h post-dose | -0.11 Log IU/mL | Standard Deviation 0.11 |
| Placebo + PEG + RIBA | Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale | 4 h post-dose | -0.07 Log IU/mL | Standard Deviation 0.07 |
Primary
Change From Baseline in QTcF Interval at Day 2 and 28
Single 12-lead electrocardiogram (ECG) was obtained. The standard ECG criteria of potential clinical importance were 1) absolute QTc Interval, \> 450 milliseconds (msec), 2) absolute PR Interval, \<110 msec, 3) absolute QRS Interval, \< 75 msec and 4) increase from baseline in QTc \> 60 msec. QTc Interval was calculated using Frederica correction formula: QTcF = QT / (RR)\^1/3. Change from Baseline was calculated by subtracting the Baseline assessment value from post Baseline visit value. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. The change from Baseline in QTc Interval at Day 2 and 28 were reported.
Time frame: Baseline (Day 1, Pre-dose ), Day 2 and Day 28
Population: Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in QTcF Interval at Day 2 and 28 | DAY 2 | 0.01 msec | Standard Deviation 17.921 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in QTcF Interval at Day 2 and 28 | DAY 28 | -5.15 msec | Standard Deviation 15.049 |
| Placebo + PEG + RIBA | Change From Baseline in QTcF Interval at Day 2 and 28 | DAY 2 | 0.82 msec | Standard Deviation 10.714 |
| Placebo + PEG + RIBA | Change From Baseline in QTcF Interval at Day 2 and 28 | DAY 28 | 9.13 msec | Standard Deviation 9.328 |
Primary
Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis
RVR was defined as the proportion of participants below the assay lower limit of detection (LOD) \<18 International units per milliliter (IU/mL) for Hepatitis C virus (HCV) ribonucleic acid (RNA) after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure . Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants.
Time frame: Day 28
Population: Intent-to-Treat Exposed population comprised of all participants who meet study criteria and were randomly assigned to treatment in the study with documented evidence of had received at least 1 dose of randomized treatment and at least 1 post-baseline HCV RNA measurement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis | HCV RNA >= Low Limit of Quantification (LLOQ) | 3 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis | Undetectable HCV RNA | 8 Participants |
| Placebo + PEG + RIBA | Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis | HCV RNA >= Low Limit of Quantification (LLOQ) | 3 Participants |
| Placebo + PEG + RIBA | Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis | Undetectable HCV RNA | 1 Participants |
Primary
Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses)
RVR was defined as the proportion of participants LOD \<18 IU/mL for HCV RNA after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure. Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants. The primary and supportive analysis differs from the nominal analysis as supportive analysis is assessed at Day 28 ± 2 (2 days visit window) whereas, the nominal analysis was assessed at Day 28.
Time frame: Day 28
Population: Intent-to-Treat Exposed population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses) | Undetectable HCV RNA | 7 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses) | HCV RNA >= LLOQ | 4 Participants |
| Placebo + PEG + RIBA | Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses) | Undetectable HCV RNA | 1 Participants |
| Placebo + PEG + RIBA | Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses) | HCV RNA >= LLOQ | 3 Participants |
Primary
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period
AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time frame: Up to Day 28
Population: Safety population was consisted of all participants who received at least 1 dose of study medication (GSK2336805 or matching placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period | Any AE | 11 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period | Any SAE | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period | Any AE | 4 Participants |
| Placebo + PEG + RIBA | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period | Any SAE | 0 Participants |
Primary
Number of Participants With HCV Genotype 1 With Virologic Response
Serum for determination of HCV genotype was collected at the screening visit. Genotype was determined by the VERSANT HCV genotype 2.0 Assay (LiPA). Number of participants with HCV genotype 1 were reported.
Time frame: Day 7, 14 and 21
Population: Intent-to-Treat Exposed population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 7, Detectable HCV RNA but < LLOQ | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 14, HCV RNA >= LLOQ | 5 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 14, Undetectable HCV RNA | 4 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 21, Undetectable HCV RNA | 7 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 7, HCV RNA >= LLOQ | 9 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 21, Detectable HCV RNA but < LLOQ | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 14, Detectable HCV RNA but < LLOQ | 2 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 21, HCV RNA >= LLOQ | 3 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 7, Undetectable HCV RNA | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 21, HCV RNA >= LLOQ | 4 Participants |
| Placebo + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 7, Undetectable HCV RNA | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 7, Detectable HCV RNA but < LLOQ | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 7, HCV RNA >= LLOQ | 4 Participants |
| Placebo + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 14, Undetectable HCV RNA | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 14, Detectable HCV RNA but < LLOQ | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 14, HCV RNA >= LLOQ | 4 Participants |
| Placebo + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 21, Undetectable HCV RNA | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With HCV Genotype 1 With Virologic Response | Day 21, Detectable HCV RNA but < LLOQ | 0 Participants |
Primary
Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed by nominal analysis was reported.
Time frame: Day 28
Population: Intent-to-Treat Exposed population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis | 0.67 Posterior probability | Standard Deviation 0.101 |
| Placebo + PEG + RIBA | Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis | 0.21 Posterior probability | Standard Deviation 0.064 |
Bayesian probability model
Primary
Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed was reported.
Time frame: Day 28
Population: Intent-to-Treat Exposed population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses | 0.62 Posterior probability | Standard Deviation 0.104 |
| Placebo + PEG + RIBA | Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses | 0.21 Posterior probability | Standard Deviation 0.064 |
Bayesian probability model
Secondary
Change From Baseline in Serum Alanine Aminotransferase Levels
Blood samples were collected at Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 for determination of serum alanine aminotransferase levels. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Day 21 | -25.9 Units per litre (U/L) | Standard Deviation 23.78 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Day 14 | -25.7 Units per litre (U/L) | Standard Deviation 20.8 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Day 28 | -24.4 Units per litre (U/L) | Standard Deviation 22.96 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Follow-up (Day 42) | -19.5 Units per litre (U/L) | Standard Deviation 25.44 |
| GSK2336805 60 mg + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Day 7 | -15.3 Units per litre (U/L) | Standard Deviation 11.67 |
| Placebo + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Follow-up (Day 42) | -19.5 Units per litre (U/L) | Standard Deviation 12.79 |
| Placebo + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Day 7 | -15.0 Units per litre (U/L) | Standard Deviation 21.79 |
| Placebo + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Day 14 | -0.5 Units per litre (U/L) | Standard Deviation 15.29 |
| Placebo + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Day 21 | -10.0 Units per litre (U/L) | Standard Deviation 15.34 |
| Placebo + PEG + RIBA | Change From Baseline in Serum Alanine Aminotransferase Levels | Day 28 | 7.0 Units per litre (U/L) | Standard Deviation 27.68 |
Secondary
Mean Apparent Clearance (CL/F) of GSK2336805
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters
Time frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
Population: Intensive PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Mean Apparent Clearance (CL/F) of GSK2336805 | 18.27 L/h | Geometric Coefficient of Variation 61.6 |
Secondary
Mean Area Under the Concentration-time Curve (AUC[0-24]), AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK2336805, at Day 1
AUC values were determined using the linear-up, log-down trapezoidal rule. The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were below quantification limit (BLQ) before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters.
Time frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)
Population: Intensive Pharmacokinetic (PK) Population comprised of all participants who received GSK2336805, undergo intensive PK sampling during part 1 (Day 1) of the study, and provide evaluable GSK2336805 PK parameters.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Mean Area Under the Concentration-time Curve (AUC[0-24]), AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK2336805, at Day 1 | AUC (0-24) | 2977.79 Nanogram (ng)*h/mL | Geometric Coefficient of Variation 56.9 |
| GSK2336805 60 mg + PEG + RIBA | Mean Area Under the Concentration-time Curve (AUC[0-24]), AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK2336805, at Day 1 | AUC(0-inf) | 3284.90 Nanogram (ng)*h/mL | Geometric Coefficient of Variation 61.6 |
Secondary
Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28
Blood samples for determination of HCV RNA levels were collected from screening, immediately prior to and 1, 2, 4, 6, and 8 h after the first dose in Part 1 (Day 1), during Part 2 on Days 2 (24 h after the Day 1 dose), 7, 14, 21, and 28, and at the post-treatment follow-up visit on Day 42. All viral load samples, with the exception of the one taken during the screening visit, were taken in duplicate. The actual time and date of each sample collection will be recorded. Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test.
Time frame: Baseline (Day 1, Pre -dose ) and Day 2 (24 h, post-dose), Day 28
Population: Intent-to-Treat Exposed population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28 | Day 2, 24 h post-dose | -2.38 Log IU/mL | Standard Deviation 1.15 |
| GSK2336805 60 mg + PEG + RIBA | Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28 | Day 28, Pre or Post AM dose | -4.78 Log IU/mL | Standard Deviation 0.39 |
| Placebo + PEG + RIBA | Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28 | Day 2, 24 h post-dose | -0.11 Log IU/mL | Standard Deviation 0.11 |
| Placebo + PEG + RIBA | Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28 | Day 28, Pre or Post AM dose | -1.99 Log IU/mL | Standard Deviation 1.36 |
Secondary
Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by non-compartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters.
Time frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
Population: Intensive PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1 | Cmax | 404.84 ng/mL | Geometric Coefficient of Variation 51.1 |
| GSK2336805 60 mg + PEG + RIBA | Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1 | C24 | 26.98 ng/mL | Geometric Coefficient of Variation 92.6 |
Secondary
Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters.
Time frame: 0 (pre-dose), 0 to 2 h, > 2 h up to 4 h, > 4 h up to 6 h, or > 6 h up to 10 h on Days 7, 14, 21 and 28
Population: Sparse PK population included all participant who received GSK2336805, underwent sparse PK sampling during part 2 of the study, and provide at least one evaluable GSK2336805 PK concentration. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 7, Predose | 37.80 ng/ml | Geometric Coefficient of Variation 3.16 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 7, >2 to 4 h | 621.40 ng/ml | Geometric Coefficient of Variation 281.43 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 7, >4 to 6 h | 314.19 ng/ml | Geometric Coefficient of Variation 2.62 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 14, Predose | 121.57 ng/ml | Geometric Coefficient of Variation 101.4 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 14, >0 to 2 h | 518.82 ng/ml | — |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 14, >2 to 4 h | 364.75 ng/ml | Geometric Coefficient of Variation 86.48 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 14, >4 to 6 h | 304.03 ng/ml | Geometric Coefficient of Variation 257.03 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 21, Predose | 484.18 ng/ml | Geometric Coefficient of Variation 610.46 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 21, >2 to 4 h | 346.00 ng/ml | Geometric Coefficient of Variation 85.51 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 21, >4 to 6 h | 546.72 ng/ml | Geometric Coefficient of Variation 442.29 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 21, >6 to 10 h | 317.49 ng/ml | — |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 28, Predose | 16.95 ng/ml | Geometric Coefficient of Variation 14.9 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 28, >0 to 2 h | 607.02 ng/ml | Geometric Coefficient of Variation 162.62 |
| GSK2336805 60 mg + PEG + RIBA | Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 | Day 28, >2 to 4 h | 402.05 ng/ml | Geometric Coefficient of Variation 198.98 |
Secondary
Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28
Blood samples for determination of HCV RNA levels were collected from screening, immediately prior to and 1, 2, 4, 6, and 8 h after the first dose in Part 1 (Day 1), during Part 2 on Days 2 (24 h after the Day 1 dose), 7, 14, 21, and 28, and at the post-treatment follow-up visit on Day 42. All viral load samples, with the exception of the one taken during the screening visit, were taken in duplicate. The actual time and date of each sample collection will be recorded. Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test.
Time frame: Baseline (Day 1, pre-dose), Day 2 (24 h, Post-dose) and Day 28
Population: Intent-to-Treat Exposed population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28 | Day 1, Pre-dose, | 6.61 Log IU/mL | Standard Deviation 0.37 |
| GSK2336805 60 mg + PEG + RIBA | Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28 | Day 2, 24 h post-dose | 4.23 Log IU/mL | Standard Deviation 1.41 |
| GSK2336805 60 mg + PEG + RIBA | Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28 | Day 28, Pre or Post ante meridian (AM) dose | 1.80 Log IU/mL | Standard Deviation 0.45 |
| Placebo + PEG + RIBA | Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28 | Day 1, Pre-dose, | 5.43 Log IU/mL | Standard Deviation 0.43 |
| Placebo + PEG + RIBA | Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28 | Day 2, 24 h post-dose | 5.33 Log IU/mL | Standard Deviation 0.4 |
| Placebo + PEG + RIBA | Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28 | Day 28, Pre or Post ante meridian (AM) dose | 3.44 Log IU/mL | Standard Deviation 1.73 |
Secondary
Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Blood samples were collected at Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 for determination of serum alanine aminotransferase levels.
Time frame: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Day 21 | 27.0 U/L |
| GSK2336805 60 mg + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Day 7 | 41.5 U/L |
| GSK2336805 60 mg + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Day 28 | 28.0 U/L |
| GSK2336805 60 mg + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Baseline | 56.0 U/L |
| GSK2336805 60 mg + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Follow-up (Day 42) | 29.0 U/L |
| GSK2336805 60 mg + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Day 14 | 28.0 U/L |
| Placebo + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Follow-up (Day 42) | 27.0 U/L |
| Placebo + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Baseline | 43.5 U/L |
| Placebo + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Day 7 | 37.0 U/L |
| Placebo + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Day 21 | 39.0 U/L |
| Placebo + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Day 28 | 48.0 U/L |
| Placebo + PEG + RIBA | Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 | Day 14 | 48.5 U/L |
Secondary
Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters
Time frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)
Population: Intensive PK Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1 | Tmax | 2.00 h |
| GSK2336805 60 mg + PEG + RIBA | Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1 | Tlag | 0.00 h |
Secondary
Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28
Abnormalities were graded according to the modified DAIDS version 1.0. Shift from Baseline to worst post Baseline toxicity grade were presented for Day 1 to Day 28. The toxicity Grades were, Grade 1: mild (no or minimal interference with usual social & functional activities); Grade 2: moderate (greater than minimal interference with usual social and functional activities); Grade 3: severe (inability to perform usual social and functional activities); Grade 4: potentially life threatening (inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death). Clinical chemistry parameters were alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatine phosphokinase, total CO2, chloride, creatinine, glucose, sodium, phosphate, potassium, total albumin, total bilirubin, and direct bilirubin. Only participants with change in toxicity grades are reported.
Time frame: Baseline (Day 1) and 28
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Aspartate aminotransferase, Grade 2 | 0 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Alanine aminotransferase, Grade 1 | 0 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Albumin, No toxicity | 11 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Albumin, Grade 1 | 0 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Aspartate aminotransferase, No toxicity | 8 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Aspartate aminotransferase, Grade 1 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Alanine aminotransferase, No toxicity | 11 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Total Bilirubin, No toxicity | 9 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Total Bilirubin, Grade 1 | 2 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Total Bilirubin, Grade 2 | 0 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Carbon dioxide, No toxicity | 8 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Carbon dioxide, Grade 1 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Creatine phosphokinase, No toxicity | 10 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Creatine phosphokinase, Grade 1 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Glucose, No toxicity | 5 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Glucose, Grade 1 | 4 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Glucose, Grade 2 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Phosphorus, inorganic, No toxicity | 8 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Phosphorus, inorganic, Grade 1 | 2 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Phosphorus, inorganic, Grade 2 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Potassium, No toxicity | 10 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Potassium, Grade 1 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Sodium, No toxicity | 9 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Sodium, Grade 2 | 2 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Sodium, No toxicity | 4 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Alanine aminotransferase, No toxicity | 2 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Creatine phosphokinase, No toxicity | 4 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Alanine aminotransferase, Grade 1 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Phosphorus, inorganic, Grade 1 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Albumin, No toxicity | 3 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Creatine phosphokinase, Grade 1 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Albumin, Grade 1 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Potassium, Grade 1 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Aspartate aminotransferase, No toxicity | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Glucose, No toxicity | 4 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Aspartate aminotransferase, Grade 1 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Phosphorus, inorganic, Grade 2 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Aspartate aminotransferase, Grade 2 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Glucose, Grade 1 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Total Bilirubin, No toxicity | 3 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Sodium, Grade 2 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Total Bilirubin, Grade 1 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Glucose, Grade 2 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Total Bilirubin, Grade 2 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Potassium, No toxicity | 3 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Carbon dioxide, No toxicity | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Phosphorus, inorganic, No toxicity | 4 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 | Carbon dioxide, Grade 1 | 1 Participants |
Secondary
Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28
Laboratory abnormalities were graded according to the modified division of AIDS ( DAIDS）version 1.0. Shift from Baseline to worst post baseline toxicity grade (where applicable) were presented for Day 1 to Day 28. The toxicity Grades were, Grade 1: mild (no or minimal interference with usual social & functional activities); Grade 2: moderate (greater than minimal interference with usual social and functional activities); Grade 3: severe (inability to perform usual social and functional activities); Grade 4: potentially life threatening (inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death). Hematology parameters were red blood cell, hemoglobin, hematocrit, platelet white blood cell count with differential leukocyte count, mean corpuscular volume, prothrombin time and international normalized ratio.
Time frame: Baseline (Day 1) to Day 28
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Lymphocytes absolute, No toxicity | 10 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Prothrombin time, No toxicity | 10 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | International normalized ratio, No toxicity | 10 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Prothrombin time, Grade 1 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Lymphocytes absolute, Grade 4 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Total neutrophils, absolute, No toxicity | 7 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Hemoglobin, Grade 2 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Total neutrophils, absolute, Grade 1 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Platelet count, No toxicity | 10 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Total neutrophils, absolute, Grade 2 | 2 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | International normalized ratio, Grade 1 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Total neutrophils, absolute, Grade 3 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Platelet count, Grade 1 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | White cell count, No toxicity | 8 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Hemoglobin, Grade 1 | 3 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | White cell count, Grade 1 | 2 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Platelet count, Grade 2 | 0 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | White cell count, Grade 2 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Hemoglobin, No toxicity | 7 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | White cell count, Grade 2 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Hemoglobin, No toxicity | 3 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Hemoglobin, Grade 1 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Hemoglobin, Grade 2 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | International normalized ratio, No toxicity | 3 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | International normalized ratio, Grade 1 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Lymphocytes absolute, No toxicity | 4 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Lymphocytes absolute, Grade 4 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Platelet count, No toxicity | 3 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Platelet count, Grade 1 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Platelet count, Grade 2 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Prothrombin time, No toxicity | 3 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Prothrombin time, Grade 1 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Total neutrophils, absolute, No toxicity | 2 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Total neutrophils, absolute, Grade 1 | 2 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Total neutrophils, absolute, Grade 2 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | Total neutrophils, absolute, Grade 3 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | White cell count, No toxicity | 3 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 | White cell count, Grade 1 | 1 Participants |
Secondary
Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
The urinalysis parameters analyzed were Leukocyte esterase, bilirubin, occult blood, glucose, ketones, nitrite, pH, specific gravity and dipstick assessments. Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important urinalysis findings at specified visit were reported. Visits where no abnormal values were observed not reported.
Time frame: Day 14, 28, Follow-up (Day 42)
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Occult blood, Follow-up | 0 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Nitrate, Day 14 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Ketone, Day 14 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Leukocytes, Day 14 | 1 Participants |
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Occult blood, Day 14 | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Leukocytes, Day 14 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Occult blood, Day 14 | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Occult blood, Follow-up | 1 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Ketone, Day 14 | 2 Participants |
| Placebo + PEG + RIBA | Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal | Nitrate, Day 14 | 1 Participants |
Secondary
Number of Participants With Vital Signs of Potential Clinical Concern
The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (\<85 and \>160 millimeter of mercury \[mmHg\]), diastolic blood pressure (\<45 and \>100 mmHg) and heart rate (\<40 and \>110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.
Time frame: Up to 42 days
Population: Safety population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK2336805 60 mg + PEG + RIBA | Number of Participants With Vital Signs of Potential Clinical Concern | 0 Participants |
| Placebo + PEG + RIBA | Number of Participants With Vital Signs of Potential Clinical Concern | 0 Participants |