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Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 With Peginterferon and Ribavirin in Chronic Hepatitis C Subjects

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ClinicalTrials.gov Identifier: NCT01439373
Recruitment Status : Completed
First Posted : September 23, 2011
Results First Posted : December 11, 2017
Last Update Posted : December 11, 2017
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hepatitis C, Chronic
Interventions Drug: GSK2336805
Drug: Pegylated interferon alfa-2a
Drug: Ribavirin
Drug: GSK2336805 Matching Placebo
Enrollment 16
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.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description Eligible participants received GSK2336805 60 milligram (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 peginterferon alfa-2a (PEG) 180 microgram (mcg) per week as subcutaneous injection (SC) and ribavirin (RIBA) 1000 mg (if <75 kilogram [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. 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.
Period Title: Monotherapy (Day 1)
Started 11 5
Completed 11 4
Not Completed 0 1
Reason Not Completed
Participant Dropped-out at Day 1 visit             0             1
Period Title: Combined With PEG and RIBA (Day 2 to 28)
Started 11 4
Completed 9 4
Not Completed 2 0
Reason Not Completed
Adverse Event             2             0
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 11 4 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Particiapnts
31 to 67 years Number Analyzed 11 participants 4 participants 15 participants
11 4 15
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 4 participants 15 participants
Female
1
   9.1%
0
   0.0%
1
   6.7%
Male
10
  90.9%
4
 100.0%
14
  93.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 4 participants 15 participants
African American/African Heritage
3
  27.3%
2
  50.0%
5
  33.3%
White - White/Caucasian/European Heritage
8
  72.7%
2
  50.0%
10
  66.7%
1.Primary Outcome
Title Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Measure Type: Count of Participants
Unit of Measure: Participants
HCV RNA >= Low Limit of Quantification (LLOQ)
3
  27.3%
3
  75.0%
Undetectable HCV RNA
8
  72.7%
1
  25.0%
2.Primary Outcome
Title Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Exposed population.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Measure Type: Count of Participants
Unit of Measure: Participants
Undetectable HCV RNA
7
  63.6%
1
  25.0%
HCV RNA >= LLOQ
4
  36.4%
3
  75.0%
3.Primary Outcome
Title Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Exposed population.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Mean (Standard Deviation)
Unit of Measure: Posterior probability
0.67  (0.101) 0.21  (0.064)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK2336805 60 mg + PEG + RIBA, Placebo + PEG + RIBA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Bayesian probability model
Comments P1= P(p805 >pPLC +0.3 | data)= 0.905. A probability of 95% (P1 > 0.95) or greater was to be considered 'substantial evidence of superiority.
Method of Estimation Estimation Parameter Mean posterior difference
Estimated Value 0.46
Parameter Dispersion
Type: Standard Deviation
Value: 0.119
Estimation Comments Posterior Distribution of Difference= p805 - pPLC, where, p805 is the RVR rate for GSK2336805 and pPLC is the RVR rate for Placebo. 95% credible set was defined as the 2.5 and 97.5 percentiles. 95% credible interval for the estimate was 0.22 to 0.68.
4.Primary Outcome
Title Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Exposed population.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Mean (Standard Deviation)
Unit of Measure: Posterior probability
0.62  (0.104) 0.21  (0.064)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK2336805 60 mg + PEG + RIBA, Placebo + PEG + RIBA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Bayesian probability model
Comments P1= P(p805 >pPLC +0.3 | data)= 0.822. A probability of 95% (P1 > 0.95) or greater was to be considered 'substantial evidence of superiority.
Method of Estimation Estimation Parameter Mean posterior difference
Estimated Value 0.41
Parameter Dispersion
Type: Standard Deviation
Value: 0.122
Estimation Comments Posterior Distribution of Difference= p805 - pPLC, where, p805 is the RVR rate for GSK2336805 and pPLC is the RVR rate for Placebo. 95% credible set was defined as the 2.5 and 97.5 percentiles. 95% credible interval for the estimate was 0.17 to 0.6
5.Primary Outcome
Title Number of Participants With HCV Genotype 1 With Virologic Response
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Exposed population.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Measure Type: Count of Participants
Unit of Measure: Participants
Day 7, Undetectable HCV RNA
1
   9.1%
0
   0.0%
Day 7, Detectable HCV RNA but < LLOQ
1
   9.1%
0
   0.0%
Day 7, HCV RNA >= LLOQ
9
  81.8%
4
 100.0%
Day 14, Undetectable HCV RNA
4
  36.4%
0
   0.0%
Day 14, Detectable HCV RNA but < LLOQ
2
  18.2%
0
   0.0%
Day 14, HCV RNA >= LLOQ
5
  45.5%
4
 100.0%
Day 21, Undetectable HCV RNA
7
  63.6%
0
   0.0%
Day 21, Detectable HCV RNA but < LLOQ
1
   9.1%
0
   0.0%
Day 21, HCV RNA >= LLOQ
3
  27.3%
4
 100.0%
6.Primary Outcome
Title Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Exposed population.
Arm/Group Title GSK2336805 60 mg (Part A) Placebo (Part A)
Hide Arm/Group Description:
Eligible participants received GSK2336805 60 mg once daily on Day 1 (Part A) of the study.
Eligible participants received matching placebo once daily on Day 1 (Part A) of the study
Overall Number of Participants Analyzed 11 4
Mean (Standard Deviation)
Unit of Measure: Log IU/mL
1 h post-dose 0.02  (0.31) -0.01  (0.06)
2 h post-dose -0.03  (0.21) -0.00  (0.07)
4 h post-dose -0.70  (0.42) -0.07  (0.07)
6 h post-dose -1.37  (0.63) 0.08  (0.15)
8 h post-dose -1.83  (0.81) 0.07  (0.11)
24 h post-dose -2.38  (1.15) -0.11  (0.11)
7.Primary Outcome
Title Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was consisted of all participants who received at least 1 dose of study medication (GSK2336805 or matching placebo).
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
11
 100.0%
4
 100.0%
Any SAE
0
   0.0%
0
   0.0%
8.Primary Outcome
Title Change From Baseline in QTcF Interval at Day 2 and 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Mean (Standard Deviation)
Unit of Measure: msec
DAY 2 Number Analyzed 11 participants 4 participants
0.01  (17.921) 0.82  (10.714)
DAY 28 Number Analyzed 10 participants 4 participants
-5.15  (15.049) 9.13  (9.328)
9.Secondary Outcome
Title Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin, No toxicity
7
  63.6%
3
  75.0%
Hemoglobin, Grade 1
3
  27.3%
1
  25.0%
Hemoglobin, Grade 2
1
   9.1%
0
   0.0%
International normalized ratio, No toxicity
10
  90.9%
3
  75.0%
International normalized ratio, Grade 1
1
   9.1%
1
  25.0%
Lymphocytes absolute, No toxicity
10
  90.9%
4
 100.0%
Lymphocytes absolute, Grade 4
1
   9.1%
0
   0.0%
Platelet count, No toxicity
10
  90.9%
3
  75.0%
Platelet count, Grade 1
1
   9.1%
0
   0.0%
Platelet count, Grade 2
0
   0.0%
1
  25.0%
Prothrombin time, No toxicity
10
  90.9%
3
  75.0%
Prothrombin time, Grade 1
1
   9.1%
1
  25.0%
Total neutrophils, absolute, No toxicity
7
  63.6%
2
  50.0%
Total neutrophils, absolute, Grade 1
1
   9.1%
2
  50.0%
Total neutrophils, absolute, Grade 2
2
  18.2%
0
   0.0%
Total neutrophils, absolute, Grade 3
1
   9.1%
0
   0.0%
White cell count, No toxicity
8
  72.7%
3
  75.0%
White cell count, Grade 1
2
  18.2%
1
  25.0%
White cell count, Grade 2
1
   9.1%
0
   0.0%
10.Secondary Outcome
Title Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine aminotransferase, No toxicity
11
 100.0%
2
  50.0%
Alanine aminotransferase, Grade 1
0
   0.0%
1
  25.0%
Albumin, No toxicity
11
 100.0%
3
  75.0%
Albumin, Grade 1
0
   0.0%
1
  25.0%
Aspartate aminotransferase, No toxicity
8
  72.7%
1
  25.0%
Aspartate aminotransferase, Grade 1
1
   9.1%
1
  25.0%
Aspartate aminotransferase, Grade 2
0
   0.0%
1
  25.0%
Total Bilirubin, No toxicity
9
  81.8%
3
  75.0%
Total Bilirubin, Grade 1
2
  18.2%
0
   0.0%
Total Bilirubin, Grade 2
0
   0.0%
1
  25.0%
Carbon dioxide, No toxicity
8
  72.7%
1
  25.0%
Carbon dioxide, Grade 1
1
   9.1%
1
  25.0%
Creatine phosphokinase, No toxicity
10
  90.9%
4
 100.0%
Creatine phosphokinase, Grade 1
1
   9.1%
0
   0.0%
Glucose, No toxicity
5
  45.5%
4
 100.0%
Glucose, Grade 1
4
  36.4%
0
   0.0%
Glucose, Grade 2
1
   9.1%
0
   0.0%
Phosphorus, inorganic, No toxicity
8
  72.7%
4
 100.0%
Phosphorus, inorganic, Grade 1
2
  18.2%
0
   0.0%
Phosphorus, inorganic, Grade 2
1
   9.1%
0
   0.0%
Potassium, No toxicity
10
  90.9%
3
  75.0%
Potassium, Grade 1
1
   9.1%
0
   0.0%
Sodium, No toxicity
9
  81.8%
4
 100.0%
Sodium, Grade 2
2
  18.2%
0
   0.0%
11.Secondary Outcome
Title Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Measure Type: Count of Participants
Unit of Measure: Participants
Occult blood, Day 14 Number Analyzed 9 participants 4 participants
0
   0.0%
1
  25.0%
Occult blood, Follow-up Number Analyzed 10 participants 4 participants
0
   0.0%
1
  25.0%
Ketone, Day 14 Number Analyzed 9 participants 4 participants
1
  11.1%
2
  50.0%
Nitrate, Day 14 Number Analyzed 9 participants 3 participants
1
  11.1%
1
  33.3%
Leukocytes, Day 14 Number Analyzed 9 participants 2 participants
1
  11.1%
1
  50.0%
12.Secondary Outcome
Title Number of Participants With Vital Signs of Potential Clinical Concern
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Exposed population. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Mean (Standard Deviation)
Unit of Measure: Log IU/mL
Day 1, Pre-dose, Number Analyzed 11 participants 4 participants
6.61  (0.37) 5.43  (0.43)
Day 2, 24 h post-dose Number Analyzed 11 participants 4 participants
4.23  (1.41) 5.33  (0.40)
Day 28, Pre or Post ante meridian (AM) dose Number Analyzed 9 participants 4 participants
1.80  (0.45) 3.44  (1.73)
14.Secondary Outcome
Title Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Exposed population. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Mean (Standard Deviation)
Unit of Measure: Log IU/mL
Day 2, 24 h post-dose Number Analyzed 11 participants 4 participants
-2.38  (1.15) -0.11  (0.11)
Day 28, Pre or Post AM dose Number Analyzed 9 participants 4 participants
-4.78  (0.39) -1.99  (1.36)
15.Secondary Outcome
Title Change From Baseline in Serum Alanine Aminotransferase Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Mean (Standard Deviation)
Unit of Measure: Units per litre (U/L)
Day 7 Number Analyzed 10 participants 3 participants
-15.3  (11.67) -15.0  (21.79)
Day 14 Number Analyzed 10 participants 4 participants
-25.7  (20.80) -0.5  (15.29)
Day 21 Number Analyzed 10 participants 4 participants
-25.9  (23.78) -10.0  (15.34)
Day 28 Number Analyzed 10 participants 4 participants
-24.4  (22.96) 7.0  (27.68)
Follow-up (Day 42) Number Analyzed 10 participants 4 participants
-19.5  (25.44) -19.5  (12.79)
16.Secondary Outcome
Title Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 11 4
Median (Full Range)
Unit of Measure: U/L
Baseline Number Analyzed 11 participants 4 participants
56.0
(24 to 95)
43.5
(29 to 93)
Day 7 Number Analyzed 10 participants 3 participants
41.5
(22 to 59)
37.0
(29 to 53)
Day 14 Number Analyzed 10 participants 4 participants
28.0
(20 to 44)
48.5
(36 to 74)
Day 21 Number Analyzed 10 participants 4 participants
27.0
(14 to 47)
39.0
(24 to 67)
Day 28 Number Analyzed 10 participants 4 participants
28.0
(16 to 58)
48.0
(19 to 122)
Follow-up (Day 42) Number Analyzed 10 participants 4 participants
29.0
(19 to 48)
27.0
(20 to 57)
17.Secondary Outcome
Title 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
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title GSK2336805 60 mg (Part A)
Hide Arm/Group Description:
Eligible participants received GSK2336805 60 mg once daily on Day 1 (Part A) of the study
Overall Number of Participants Analyzed 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram (ng)*h/mL
AUC (0-24)
2977.79
(56.9%)
AUC(0-inf)
3284.90
(61.6%)
18.Secondary Outcome
Title Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intensive PK Population.
Arm/Group Title GSK2336805 60 mg (Part A)
Hide Arm/Group Description:
Eligible participants received GSK2336805 60 mg once daily on Day 1 (Part A) of the study
Overall Number of Participants Analyzed 11
Median (Full Range)
Unit of Measure: h
Tmax
2.00
(0.517 to 4.067)
Tlag
0.00
(0.00 to 0.00)
19.Secondary Outcome
Title Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intensive PK Population.
Arm/Group Title GSK2336805 60 mg (Part A)
Hide Arm/Group Description:
Eligible participants received GSK2336805 60 mg once daily on Day 1 (Part A) of the study
Overall Number of Participants Analyzed 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cmax
404.84
(51.1%)
C24
26.98
(92.6%)
20.Secondary Outcome
Title Mean Apparent Clearance (CL/F) of GSK2336805
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intensive PK Population.
Arm/Group Title GSK2336805 60 mg
Hide Arm/Group Description:
Eligible participants received GSK2336805 60 mg once daily on Day 1 (Part A) of the study
Overall Number of Participants Analyzed 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
18.27
(61.6%)
21.Secondary Outcome
Title Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title GSK2336805 60 mg (Part A)
Hide Arm/Group Description:
Eligible participants received GSK2336805 60 mg once daily on Day 1 (Part A) of the study
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/ml
Day 7, Predose Number Analyzed 2 participants
37.80
(3.16%)
Day 7, >2 to 4 h Number Analyzed 5 participants
621.40
(281.43%)
Day 7, >4 to 6 h Number Analyzed 2 participants
314.19
(2.62%)
Day 14, Predose Number Analyzed 2 participants
121.57
(101.40%)
Day 14, >0 to 2 h Number Analyzed 1 participants
518.82 [1] 
(NA%)
Day 14, >2 to 4 h Number Analyzed 3 participants
364.75
(86.48%)
Day 14, >4 to 6 h Number Analyzed 3 participants
304.03
(257.03%)
Day 21, Predose Number Analyzed 2 participants
484.18
(610.46%)
Day 21, >2 to 4 h Number Analyzed 3 participants
346.00
(85.51%)
Day 21, >4 to 6 h Number Analyzed 2 participants
546.72
(442.29%)
Day 21, >6 to 10 h Number Analyzed 1 participants
317.49 [1] 
(NA%)
Day 28, Predose Number Analyzed 3 participants
16.95
(14.90%)
Day 28, >0 to 2 h Number Analyzed 2 participants
607.02
(162.62%)
Day 28, >2 to 4 h Number Analyzed 9 participants
402.05
(198.98%)
[1]
Only one participant was available for analysis therefore, dispersion was not calculated.
Time Frame AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Adverse Event Reporting Description Safety population was used for collection of the AEs
 
Arm/Group Title GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Hide Arm/Group Description 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. 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.
All-Cause Mortality
GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Affected / at Risk (%) Affected / at Risk (%)
Total   0/11 (0.00%)   0/4 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Affected / at Risk (%) Affected / at Risk (%)
Total   0/11 (0.00%)   0/4 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
GSK2336805 60 mg + PEG + RIBA Placebo + PEG + RIBA
Affected / at Risk (%) Affected / at Risk (%)
Total   11/11 (100.00%)   4/4 (100.00%) 
Blood and lymphatic system disorders     
ANAEMIA  1  3/11 (27.27%)  0/4 (0.00%) 
LEUKOPENIA  1  2/11 (18.18%)  0/4 (0.00%) 
LYMPHOPENIA  1  1/11 (9.09%)  0/4 (0.00%) 
NEUTROPENIA  1  3/11 (27.27%)  0/4 (0.00%) 
THROMBOCYTOPENIA  1  2/11 (18.18%)  0/4 (0.00%) 
Gastrointestinal disorders     
DIARRHOEA  1  0/11 (0.00%)  1/4 (25.00%) 
HAEMORRHOIDAL HAEMORRHAGE  1  0/11 (0.00%)  1/4 (25.00%) 
NAUSEA  1  4/11 (36.36%)  0/4 (0.00%) 
VOMITING  1  2/11 (18.18%)  0/4 (0.00%) 
General disorders     
PYREXIA  1  0/11 (0.00%)  1/4 (25.00%) 
CHILLS  1  2/11 (18.18%)  0/4 (0.00%) 
FATIGUE  1  5/11 (45.45%)  1/4 (25.00%) 
PAIN  1  1/11 (9.09%)  1/4 (25.00%) 
Hepatobiliary disorders     
HYPERBILIRUBINAEMIA  1  1/11 (9.09%)  0/4 (0.00%) 
Infections and infestations     
BACTERAEMIA  1  0/11 (0.00%)  1/4 (25.00%) 
FOLLICULITIS  1  2/11 (18.18%)  0/4 (0.00%) 
PNEUMONIA  1  1/11 (9.09%)  0/4 (0.00%) 
UPPER RESPIRATORY TRACT INFECTION  1  1/11 (9.09%)  0/4 (0.00%) 
URINARY TRACT INFECTION  1  0/11 (0.00%)  1/4 (25.00%) 
Investigations     
INTERNATIONAL NORMALISED RATIO INCREASED  1  1/11 (9.09%)  0/4 (0.00%) 
ALANINE AMINOTRANSFERASE INCREASED  1  0/11 (0.00%)  1/4 (25.00%) 
ASPARTATE AMINOTRANSFERASE INCREASED  1  0/11 (0.00%)  1/4 (25.00%) 
BLOOD BICARBONATE DECREASED  1  0/11 (0.00%)  1/4 (25.00%) 
BLOOD PHOSPHORUS DECREASED  1  1/11 (9.09%)  0/4 (0.00%) 
CARBON DIOXIDE DECREASED  1  1/11 (9.09%)  0/4 (0.00%) 
HAEMATOCRIT DECREASED  1  1/11 (9.09%)  0/4 (0.00%) 
HAEMOGLOBIN DECREASED  1  1/11 (9.09%)  0/4 (0.00%) 
NEUTROPHIL COUNT DECREASED  1  1/11 (9.09%)  1/4 (25.00%) 
PLATELET COUNT DECREASED  1  0/11 (0.00%)  1/4 (25.00%) 
WHITE BLOOD CELL COUNT DECREASED  1  0/11 (0.00%)  1/4 (25.00%) 
Metabolism and nutrition disorders     
DECREASED APPETITE  1  0/11 (0.00%)  1/4 (25.00%) 
Musculoskeletal and connective tissue disorders     
MUSCLE SPASMS  1  1/11 (9.09%)  0/4 (0.00%) 
MUSCULOSKELETAL STIFFNESS  1  0/11 (0.00%)  1/4 (25.00%) 
MYALGIA  1  1/11 (9.09%)  0/4 (0.00%) 
Nervous system disorders     
DYSGEUSIA  1  1/11 (9.09%)  0/4 (0.00%) 
Psychiatric disorders     
INSOMNIA  1  1/11 (9.09%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
COUGH  1  2/11 (18.18%)  0/4 (0.00%) 
1
Term from vocabulary, MedDRA, Version 14.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01439373     History of Changes
Other Study ID Numbers: 115519
First Submitted: July 7, 2011
First Posted: September 23, 2011
Results First Submitted: September 26, 2017
Results First Posted: December 11, 2017
Last Update Posted: December 11, 2017