ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.

Participant Flow for 2 periods

Period 1:   Monotherapy (Day 1)
    GSK2336805 60 mg + PEG + RIBA   Placebo + PEG + RIBA
STARTED   11   5 
COMPLETED   11   4 
NOT COMPLETED   0   1 
Participant Dropped-out at Day 1 visit                0                1 

Period 2:   Combined With PEG and RIBA (Day 2 to 28)
    GSK2336805 60 mg + PEG + RIBA   Placebo + PEG + RIBA
STARTED   11   4 
COMPLETED   9   4 
NOT COMPLETED   2   0 
Adverse Event                2                0 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
GSK2336805 60 mg + PEG + RIBA Eligible participants received GSK2336805 60 mg orally once daily on Day 1 (Part A) of the study. Part 2 of the study then proceeded without interruption with the co-administration of GSK2336805 60 mg once daily with PEG 180 mcg per week as SC and RIBA 1000 mg (if <75 kg) or 1200 mg (if <75 kg) orally in 2 divided doses with food (morning and evening) (2 or three 200 mg tablets in the morning and three 200 mg tablets in the evening) through 4 weeks of treatment from Day 2 through Day 28 of the study.
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.
Total Total of all reporting groups

Baseline Measures
   GSK2336805 60 mg + PEG + RIBA   Placebo + PEG + RIBA   Total 
Overall Participants Analyzed 
[Units: Participants]
 11   4   15 
Age, Customized 
[Units: Particiapnts]
     
31 to 67 years   11   4   15 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      1   9.1%      0   0.0%      1   6.7% 
Male      10  90.9%      4 100.0%      14  93.3% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
     
African American/African Heritage   3   2   5 
White - White/Caucasian/European Heritage   8   2   10 


  Outcome Measures

1.  Primary:   Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis   [ Time Frame: Day 28 ]

2.  Primary:   Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses)   [ Time Frame: Day 28 ]

3.  Primary:   Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis   [ Time Frame: Day 28 ]

4.  Primary:   Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses   [ Time Frame: Day 28 ]

5.  Primary:   Number of Participants With HCV Genotype 1 With Virologic Response   [ Time Frame: Day 7, 14 and 21 ]

6.  Primary:   Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale   [ Time Frame: Day 1 (Baseline [Pre-dose], 1, 2, 4, 6, and 8 and 24 h) ]

7.  Primary:   Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period   [ Time Frame: Up to Day 28 ]

8.  Primary:   Change From Baseline in QTcF Interval at Day 2 and 28   [ Time Frame: Baseline (Day 1, Pre-dose ), Day 2 and Day 28 ]

9.  Secondary:   Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28   [ Time Frame: Baseline (Day 1) to Day 28 ]

10.  Secondary:   Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28   [ Time Frame: Baseline (Day 1) and 28 ]

11.  Secondary:   Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal   [ Time Frame: Day 14, 28, Follow-up (Day 42) ]

12.  Secondary:   Number of Participants With Vital Signs of Potential Clinical Concern   [ Time Frame: Up to 42 days ]

13.  Secondary:   Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28   [ Time Frame: Baseline (Day 1, pre-dose), Day 2 (24 h, Post-dose) and Day 28 ]

14.  Secondary:   Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28   [ Time Frame: Baseline (Day 1, Pre -dose ) and Day 2 (24 h, post-dose), Day 28 ]

15.  Secondary:   Change From Baseline in Serum Alanine Aminotransferase Levels   [ Time Frame: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 ]

16.  Secondary:   Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42   [ Time Frame: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 ]

17.  Secondary:   Mean Area Under the Concentration-time Curve (AUC[0-24]), AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK2336805, at Day 1   [ Time Frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2) ]

18.  Secondary:   Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1   [ Time Frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2) ]

19.  Secondary:   Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1   [ Time Frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1) ]

20.  Secondary:   Mean Apparent Clearance (CL/F) of GSK2336805   [ Time Frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1) ]

21.  Secondary:   Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28   [ 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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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