Trial Outcomes & Findings for Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 With Peginterferon and Ribavirin in Chronic Hepatitis C Subjects (NCT NCT01439373)
NCT ID: NCT01439373
Last Updated: 2017-12-11
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
16 participants
Primary outcome timeframe
Day 28
Results posted on
2017-12-11
Participant Flow
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.
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.
Participant milestones
| Measure |
GSK2336805 60 mg + PEG + RIBA
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.
|
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.
|
|---|---|---|
|
Monotherapy (Day 1)
STARTED
|
11
|
5
|
|
Monotherapy (Day 1)
COMPLETED
|
11
|
4
|
|
Monotherapy (Day 1)
NOT COMPLETED
|
0
|
1
|
|
Combined With PEG and RIBA (Day 2 to 28)
STARTED
|
11
|
4
|
|
Combined With PEG and RIBA (Day 2 to 28)
COMPLETED
|
9
|
4
|
|
Combined With PEG and RIBA (Day 2 to 28)
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
GSK2336805 60 mg + PEG + RIBA
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.
|
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.
|
|---|---|---|
|
Monotherapy (Day 1)
Participant Dropped-out at Day 1 visit
|
0
|
1
|
|
Combined With PEG and RIBA (Day 2 to 28)
Adverse Event
|
2
|
0
|
Baseline Characteristics
Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 With Peginterferon and Ribavirin in Chronic Hepatitis C Subjects
Baseline characteristics by cohort
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
31 to 67 years
|
11 Particiapnts
n=5 Participants
|
4 Particiapnts
n=7 Participants
|
15 Particiapnts
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 28Population: 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.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis
HCV RNA >= Low Limit of Quantification (LLOQ)
|
3 Participants
|
3 Participants
|
|
Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis
Undetectable HCV RNA
|
8 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 28Population: Intent-to-Treat Exposed population.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses)
Undetectable HCV RNA
|
7 Participants
|
1 Participants
|
|
Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses)
HCV RNA >= LLOQ
|
4 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Day 28Population: Intent-to-Treat Exposed population.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis
|
0.67 Posterior probability
Standard Deviation 0.101
|
0.21 Posterior probability
Standard Deviation 0.064
|
PRIMARY outcome
Timeframe: Day 28Population: Intent-to-Treat Exposed population.
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed was reported.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses
|
0.62 Posterior probability
Standard Deviation 0.104
|
0.21 Posterior probability
Standard Deviation 0.064
|
PRIMARY outcome
Timeframe: Day 7, 14 and 21Population: Intent-to-Treat Exposed population.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Number of Participants With HCV Genotype 1 With Virologic Response
Day 21, HCV RNA >= LLOQ
|
3 Participants
|
4 Participants
|
|
Number of Participants With HCV Genotype 1 With Virologic Response
Day 7, Undetectable HCV RNA
|
1 Participants
|
0 Participants
|
|
Number of Participants With HCV Genotype 1 With Virologic Response
Day 7, Detectable HCV RNA but < LLOQ
|
1 Participants
|
0 Participants
|
|
Number of Participants With HCV Genotype 1 With Virologic Response
Day 7, HCV RNA >= LLOQ
|
9 Participants
|
4 Participants
|
|
Number of Participants With HCV Genotype 1 With Virologic Response
Day 14, Undetectable HCV RNA
|
4 Participants
|
0 Participants
|
|
Number of Participants With HCV Genotype 1 With Virologic Response
Day 14, Detectable HCV RNA but < LLOQ
|
2 Participants
|
0 Participants
|
|
Number of Participants With HCV Genotype 1 With Virologic Response
Day 14, HCV RNA >= LLOQ
|
5 Participants
|
4 Participants
|
|
Number of Participants With HCV Genotype 1 With Virologic Response
Day 21, Undetectable HCV RNA
|
7 Participants
|
0 Participants
|
|
Number of Participants With HCV Genotype 1 With Virologic Response
Day 21, Detectable HCV RNA but < LLOQ
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 (Baseline [Pre-dose], 1, 2, 4, 6, and 8 and 24 h)Population: Intent-to-Treat Exposed population.
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).
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
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
|
-0.01 Log IU/mL
Standard Deviation 0.06
|
|
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
|
-0.00 Log IU/mL
Standard Deviation 0.07
|
|
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
|
-0.07 Log IU/mL
Standard Deviation 0.07
|
|
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
|
0.08 Log IU/mL
Standard Deviation 0.15
|
|
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
|
0.07 Log IU/mL
Standard Deviation 0.11
|
|
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
|
-0.11 Log IU/mL
Standard Deviation 0.11
|
PRIMARY outcome
Timeframe: Up to Day 28Population: Safety population was consisted of all participants who received at least 1 dose of study medication (GSK2336805 or matching placebo).
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period
Any AE
|
11 Participants
|
4 Participants
|
|
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period
Any SAE
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1, Pre-dose ), Day 2 and Day 28Population: Safety population.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Change From Baseline in QTcF Interval at Day 2 and 28
DAY 2
|
0.01 msec
Standard Deviation 17.921
|
0.82 msec
Standard Deviation 10.714
|
|
Change From Baseline in QTcF Interval at Day 2 and 28
DAY 28
|
-5.15 msec
Standard Deviation 15.049
|
9.13 msec
Standard Deviation 9.328
|
SECONDARY outcome
Timeframe: Baseline (Day 1) to Day 28Population: Safety population.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
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
|
3 Participants
|
|
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
|
1 Participants
|
|
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
|
0 Participants
|
|
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
|
3 Participants
|
|
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
|
1 Participants
|
|
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
|
4 Participants
|
|
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
|
0 Participants
|
|
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
|
3 Participants
|
|
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
|
0 Participants
|
|
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
|
1 Participants
|
|
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
|
3 Participants
|
|
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
|
1 Participants
|
|
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
|
2 Participants
|
|
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
|
2 Participants
|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
3 Participants
|
|
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
|
1 Participants
|
|
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
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and 28Population: Safety population.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
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
|
2 Participants
|
|
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
|
1 Participants
|
|
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
|
3 Participants
|
|
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
|
1 Participants
|
|
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
|
1 Participants
|
|
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
|
1 Participants
|
|
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
|
1 Participants
|
|
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
|
3 Participants
|
|
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
|
0 Participants
|
|
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
|
1 Participants
|
|
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
|
1 Participants
|
|
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
|
1 Participants
|
|
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
|
4 Participants
|
|
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
|
0 Participants
|
|
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
|
4 Participants
|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
4 Participants
|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
3 Participants
|
|
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
|
0 Participants
|
|
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
|
4 Participants
|
|
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
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 14, 28, Follow-up (Day 42)Population: Safety population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
Occult blood, Day 14
|
0 Participants
|
1 Participants
|
|
Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
Occult blood, Follow-up
|
0 Participants
|
1 Participants
|
|
Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
Ketone, Day 14
|
1 Participants
|
2 Participants
|
|
Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
Nitrate, Day 14
|
1 Participants
|
1 Participants
|
|
Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
Leukocytes, Day 14
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 42 daysPopulation: Safety population.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Number of Participants With Vital Signs of Potential Clinical Concern
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose), Day 2 (24 h, Post-dose) and Day 28Population: Intent-to-Treat Exposed population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
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
|
5.43 Log IU/mL
Standard Deviation 0.43
|
|
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
|
5.33 Log IU/mL
Standard Deviation 0.40
|
|
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
|
3.44 Log IU/mL
Standard Deviation 1.73
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre -dose ) and Day 2 (24 h, post-dose), Day 28Population: Intent-to-Treat Exposed population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
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
|
-0.11 Log IU/mL
Standard Deviation 0.11
|
|
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
|
-1.99 Log IU/mL
Standard Deviation 1.36
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42Population: Safety population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Change From Baseline in Serum Alanine Aminotransferase Levels
Day 7
|
-15.3 Units per litre (U/L)
Standard Deviation 11.67
|
-15.0 Units per litre (U/L)
Standard Deviation 21.79
|
|
Change From Baseline in Serum Alanine Aminotransferase Levels
Day 14
|
-25.7 Units per litre (U/L)
Standard Deviation 20.80
|
-0.5 Units per litre (U/L)
Standard Deviation 15.29
|
|
Change From Baseline in Serum Alanine Aminotransferase Levels
Day 21
|
-25.9 Units per litre (U/L)
Standard Deviation 23.78
|
-10.0 Units per litre (U/L)
Standard Deviation 15.34
|
|
Change From Baseline in Serum Alanine Aminotransferase Levels
Day 28
|
-24.4 Units per litre (U/L)
Standard Deviation 22.96
|
7.0 Units per litre (U/L)
Standard Deviation 27.68
|
|
Change From Baseline in Serum Alanine Aminotransferase Levels
Follow-up (Day 42)
|
-19.5 Units per litre (U/L)
Standard Deviation 25.44
|
-19.5 Units per litre (U/L)
Standard Deviation 12.79
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42Population: Safety Population. Only those participants available at the specified time points were analyzed.
Blood samples were collected at Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 for determination of serum alanine aminotransferase levels.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
Placebo + PEG + RIBA
n=4 Participants
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.
|
|---|---|---|
|
Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Day 21
|
27.0 U/L
Interval 14.0 to 47.0
|
39.0 U/L
Interval 24.0 to 67.0
|
|
Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Baseline
|
56.0 U/L
Interval 24.0 to 95.0
|
43.5 U/L
Interval 29.0 to 93.0
|
|
Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Day 7
|
41.5 U/L
Interval 22.0 to 59.0
|
37.0 U/L
Interval 29.0 to 53.0
|
|
Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Day 14
|
28.0 U/L
Interval 20.0 to 44.0
|
48.5 U/L
Interval 36.0 to 74.0
|
|
Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Day 28
|
28.0 U/L
Interval 16.0 to 58.0
|
48.0 U/L
Interval 19.0 to 122.0
|
|
Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Follow-up (Day 42)
|
29.0 U/L
Interval 19.0 to 48.0
|
27.0 U/L
Interval 20.0 to 57.0
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
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.
|
|---|---|---|
|
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
|
—
|
|
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 outcome
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)Population: Intensive PK Population.
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
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
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.
|
|---|---|---|
|
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
Interval 0.517 to 4.067
|
—
|
|
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
Interval 0.0 to 0.0
|
—
|
SECONDARY outcome
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)Population: Intensive PK Population.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
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.
|
|---|---|---|
|
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
|
—
|
|
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 outcome
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)Population: Intensive PK Population.
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
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 Participants
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.
|
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.
|
|---|---|---|
|
Mean Apparent Clearance (CL/F) of GSK2336805
|
18.27 L/h
Geometric Coefficient of Variation 61.6
|
—
|
SECONDARY outcome
Timeframe: 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 28Population: 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.
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.
Outcome measures
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=10 Participants
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.
|
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.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 101.40
|
—
|
|
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
Geometric Coefficient of Variation NA
Only one participant was available for analysis therefore, dispersion was not calculated.
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
Geometric Coefficient of Variation NA
Only one participant was available for analysis therefore, dispersion was not calculated.
|
—
|
|
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 14.90
|
—
|
|
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
|
—
|
|
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
|
—
|
Adverse Events
GSK2336805 60 mg + PEG + RIBA
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Placebo + PEG + RIBA
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
GSK2336805 60 mg + PEG + RIBA
n=11 participants at risk
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.
|
Placebo + PEG + RIBA
n=4 participants at risk
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.
|
|---|---|---|
|
General disorders
PYREXIA
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
INTERNATIONAL NORMALISED RATIO INCREASED
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Blood and lymphatic system disorders
ANAEMIA
|
27.3%
3/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
18.2%
2/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Blood and lymphatic system disorders
LYMPHOPENIA
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
27.3%
3/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
18.2%
2/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Gastrointestinal disorders
HAEMORRHOIDAL HAEMORRHAGE
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Gastrointestinal disorders
NAUSEA
|
36.4%
4/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Gastrointestinal disorders
VOMITING
|
18.2%
2/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
General disorders
CHILLS
|
18.2%
2/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
General disorders
FATIGUE
|
45.5%
5/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
General disorders
PAIN
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Infections and infestations
BACTERAEMIA
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Infections and infestations
FOLLICULITIS
|
18.2%
2/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Infections and infestations
PNEUMONIA
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
BLOOD BICARBONATE DECREASED
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
BLOOD PHOSPHORUS DECREASED
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
CARBON DIOXIDE DECREASED
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
HAEMATOCRIT DECREASED
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
HAEMOGLOBIN DECREASED
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
PLATELET COUNT DECREASED
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL STIFFNESS
|
0.00%
0/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
25.0%
1/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Nervous system disorders
DYSGEUSIA
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Psychiatric disorders
INSOMNIA
|
9.1%
1/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
18.2%
2/11 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
0.00%
0/4 • AEs were collected till end of the follow-up period (Day 42). On treatment SAE and non-SAEs were reported.
Safety population was used for collection of the AEs
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER