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Dose Ranging of GSK2336805 in Combination Therapy (HAI115879)

This study has been completed.
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01648140
First received: July 12, 2012
Last updated: April 25, 2017
Last verified: November 2016
Results First Received: April 25, 2017  
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 40 mg
Drug: GSK2336805 60 mg
Drug: Pegylated interferon alpha-2a
Drug: Ribavirin
Drug: Telaprevir

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted across 29 centers in 6 countries (United States, Puerto Rico, Germany, Belgium, France, and Bulgaria) from 15 August 2012 to 16 July 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with treatment-naïve(TN) chronic genotype1(G1) hepatitis C virus (HCV) infection were randomly allocated on 2:2:1 basis to 2 dose levels of GSK2336805 or telaprevir. In a nonrandomized single-arm cohort, participants with TN genotype4(G4) chronic HCV infection were enrolled in parallel at dose level of 60 milligrams (mg) of GSK2336805.

Reporting Groups
  Description
GSK2336805 40 mg, G1 HCV Participants with chronic G1 HCV infection received GSK2336805 40 mg orally (20 mg x 2 tablets) once daily in the morning with food in combination with antiviral therapy (Pegylated Interferon Alfa-2a [PEG] + Ribavirin [RIBA]) for 12 weeks followed by PEG and RIBA alone for either 12 or 36 weeks based on the extended rapid virologic response (eRVR) achievement. PEG dose was 180 micrograms (µg) once weekly subcutaneous (SC) injection and the RIBA dose was 1000 mg orally (200 mg x 5 capsules) (if body weight was <75 kilogram [kg]) or 1200 mg orally (200 mg x 6 capsules) (if body weight was >=75 kg) taken in 2 divided doses with food.
GSK2336805 60 mg, G1 HCV Participants with chronic G1 HCV infection received GSK2336805 60 mg orally (30 mg x 2 tablets) once daily in the morning with food in combination with antiviral therapy (PEG+RIBA) for 12 weeks followed by PEG and RIBA alone for either 12 or 36 weeks based on eRVR achievement. PEG dose was 180 µg once weekly SC injection and the RIBA dose was 1000 mg orally (200 mg x 5 capsules) (if body weight was <75 kg) or 1200 mg orally (200 mg x 6 capsules) (if body weight was >=75 kg) taken orally in 2 divided doses with food.
Telaprevir, G1 HCV Participants with chronic G1 HCV infection received two telaprevir 375 mg tablets orally 3 times a day (7 to 9 hours apart) with food containing approximately 20 grams of fat in combination with antiviral therapy (PEG+RIBA) for 12 weeks followed by PEG and RIBA alone for either 12 or 36 weeks based on eRVR achievement. PEG dose was 180 µg once weekly SC injection and the RIBA dose was 1000 mg orally (200 mg x 5 capsules) (if body weight was <75 kg) or 1200 mg orally (200 mg x 6 capsules) (if body weight was >=75 kg) taken orally in 2 divided doses with food.
GSK2336805 60 mg, G4 HCV Participants with chronic G4 HCV infection received GSK2336805 60 mg orally (30 mg x 2 tablets) once daily in the morning with food in combination with antiviral therapy (PEG+RIBA) for 12 weeks followed by PEG and RIBA alone for either 12 or 36 weeks based on eRVR achievement. PEG dose was 180 µg once weekly SC injection and the RIBA dose was 1000 mg orally (200 mg x 5 capsules) (if body weight was <75 kg) or 1200 mg orally (200 mg x 6 capsules) (if body weight was >=75 kg) taken orally in 2 divided doses with food.

Participant Flow:   Overall Study
    GSK2336805 40 mg, G1 HCV   GSK2336805 60 mg, G1 HCV   Telaprevir, G1 HCV   GSK2336805 60 mg, G4 HCV
STARTED   41   40   17   13 
COMPLETED   29   28   9   11 
NOT COMPLETED   12   12   8   2 
Physician Decision                1                0                0                0 
Lack of Efficacy                4                7                1                0 
Adverse Event                3                1                2                0 
Withdrawal by Subject                2                3                3                2 
Lost to Follow-up                2                1                2                0 



  Baseline Characteristics
  Hide 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 40 mg, Genotype 1 HCV Participants with chronic G1 HCV infection received GSK2336805 40 mg orally (20 mg x 2 tablets) once daily in the morning with food in combination with antiviral therapy (PEG + RIBA) for 12 weeks followed by PEG and RIBA alone for either 12 or 36 weeks based on the eRVR achievement. PEG dose was 180 µg once weekly SC injection and the RIBA dose was 1000 mg orally (200 mg x 5 capsules) (if body weight was <75 kg) or 1200 mg orally (200 mg x 6 capsules) (if body weight was >=75 kg) taken in 2 divided doses with food.
GSK2336805 60 mg, Genotype 1 HCV Participants with chronic G1 HCV infection received GSK2336805 60 mg orally (30 mg x 2 tablets) once daily in the morning with food in combination with antiviral therapy (PEG+RIBA) for 12 weeks followed by PEG and RIBA alone for either 12 or 36 weeks based on eRVR achievement. PEG dose was 180 µg once weekly SC injection and the RIBA dose was 1000 mg orally (200 mg x 5 capsules) (if body weight was <75 kg) or 1200 mg orally (200 mg x 6 capsules) (if body weight was >=75 kg) taken orally in 2 divided doses with food.
Telaprevir, Genotype 1 HCV Participants with chronic G1 HCV infection received two telaprevir 375 mg tablets orally 3 times a day (7 to 9 hours apart) with food containing approximately 20 grams of fat in combination with antiviral therapy (PEG+RIBA) for 12 weeks followed by PEG and RIBA alone for either 12 or 36 weeks based on eRVR achievement. PEG dose was 180 µg once weekly SC injection and the RIBA dose was 1000 mg orally (200 mg x 5 capsules) (if body weight was <75 kg) or 1200 mg orally (200 mg x 6 capsules) (if body weight was >=75 kg) taken orally in 2 divided doses with food.
GSK2336805 60 mg, Genotype 4 HCV Participants with chronic G4 HCV infection received GSK2336805 60 mg orally (30 mg x 2 tablets) once daily in the morning with food in combination with antiviral therapy (PEG+RIBA) for 12 weeks followed by PEG and RIBA alone for either 12 or 36 weeks based on eRVR achievement. PEG dose was 180 µg once weekly SC injection and the RIBA dose was 1000 mg orally (200 mg x 5 capsules) (if body weight was <75 kg) or 1200 mg orally (200 mg x 6 capsules) (if body weight was >=75 kg) taken orally in 2 divided doses with food.
Total Total of all reporting groups

Baseline Measures
   GSK2336805 40 mg, Genotype 1 HCV   GSK2336805 60 mg, Genotype 1 HCV   Telaprevir, Genotype 1 HCV   GSK2336805 60 mg, Genotype 4 HCV   Total 
Overall Participants Analyzed 
[Units: Participants]
 41   40   17   13   111 
Age 
[Units: Years]
Mean (Standard Deviation)
 43.7  (13.23)   40.8  (9.87)   39.4  (12.02)   45.3  (11.46)   42.2  (11.73) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female      13  31.7%      16  40.0%      6  35.3%      3  23.1%      38  34.2% 
Male      28  68.3%      24  60.0%      11  64.7%      10  76.9%      73  65.8% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
         
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Asian      0   0.0%      0   0.0%      0   0.0%      1   7.7%      1   0.9% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American      6  14.6%      6  15.0%      2  11.8%      3  23.1%      17  15.3% 
White      34  82.9%      33  82.5%      15  88.2%      9  69.2%      91  82.0% 
More than one race      1   2.4%      1   2.5%      0   0.0%      0   0.0%      2   1.8% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Achieving eRVR   [ Time Frame: Week 4 and Week 12 ]

2.  Primary:   Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) up to Week 12   [ Time Frame: From the start of study treatment up to Week 12 ]

3.  Primary:   Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) up to 12-week treatment period ]

4.  Primary:   Mean Change From Baseline in Heart Rate at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Day 2, Weeks 1, 2, 4, 6, 8, and 12 ]

5.  Primary:   Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

6.  Primary:   Mean Change From Baseline in Red Blood Cell Count at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

7.  Primary:   Mean Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

8.  Primary:   Mean Change From Baseline in Hematocrit at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

9.  Primary:   Mean Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

10.  Primary:   Mean Change From Baseline in Albumin at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

11.  Primary:   Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase (CK) and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

12.  Primary:   Mean Change From Baseline in Direct Bilirubin, Total Bilirubin and Creatinine at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

13.  Primary:   Mean Change From Baseline in Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

14.  Primary:   Mean Change From Baseline in Creatinine Clearance at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12 ]

15.  Primary:   Number of Participants With Shift From Baseline in Urinalysis Data up to Week 12   [ Time Frame: Baseline (Week 0), Weeks 2 and 12 ]

16.  Primary:   Mean Change From Baseline in Electrocardiographic (ECG) Heart Rate Values at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1 and 12 ]

17.  Primary:   Mean Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval and QT Interval Corrected Bazett's Formula (QTcB), QT Interval Corrected Using Fridericia’s Formula (QTcF) Values at the Indicated Time Points up to Week 12   [ Time Frame: Baseline (Week 0) and Weeks 1 and 12 ]

18.  Secondary:   Number of Participants With Any AEs and Any SAEs After Week 12   [ Time Frame: From Week 12 up to PT Week 24 FU ]

19.  Secondary:   Number of Participants Achieving Very Rapid Virologic Response (vRVR), Rapid Virologic Response (RVR), Complete Early Virologic Response (cEVR), Sustained Virologic Response 12 and 24 (SVR12 and SVR24) With Response Guided Treatment (RGT)   [ Time Frame: From the start of the treatment up to PT FU Week 24 ]

20.  Secondary:   Mean GSK2336805 Plasma Concentrations on Day 1, Day 2, Week 4, and Week 12   [ Time Frame: Day 1, Day 2, Week 4, and Week 12 ]

21.  Secondary:   Maximum Plasma Concentration (Cmax) and Concentration at the End of the Dosing Interval (Ctau) of GSK2336805 at Week 4   [ Time Frame: Week 4 (24 h post dose) ]

22.  Secondary:   Time of Maximal Plasma Concentration (Tmax) of GSK2336805 at Week 4   [ Time Frame: Week 4 (24 h post dose) ]

23.  Secondary:   Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) at Week 4   [ Time Frame: Week 4 (24 h post dose) ]

24.  Secondary:   Apparent Clearance (CL/F) at Week 4   [ Time Frame: Week 4 (24 h post dose) ]

25.  Secondary:   Apparent Volume of Distribution (Vz/F) at Week 4   [ Time Frame: Week 4 (24 h post dose) ]

26.  Secondary:   Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

27.  Secondary:   Mean Change From Baseline in Red Blood Cell Count at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

28.  Secondary:   Mean Change From Baseline in Hemoglobin at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

29.  Secondary:   Mean Change From Baseline in Hematocrit at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

30.  Secondary:   Mean Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

31.  Secondary:   Mean Change From Baseline in Albumin at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

32.  Secondary:   Mean Change From Baseline in ALP, ALT, AST, CK and GGT at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

33.  Secondary:   Mean Change From Baseline in Total Bilirubin and Creatinine at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

34.  Secondary:   Mean Change From Baseline in SBP and DBP at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

35.  Secondary:   Mean Change From Baseline in Heart Rate at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

36.  Secondary:   Mean Change From Baseline in ECG Heart Rate Values at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

37.  Secondary:   Mean Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QTcB, QTcF Values at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

38.  Secondary:   Mean Change From Baseline in Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/BUN at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

39.  Secondary:   Mean Change From Baseline in Creatinine Clearance at the Indicated Time Points After Week 12   [ Time Frame: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4 ]

40.  Secondary:   Correlation of Individual GSK2336805 Dose With Week 4 Plasma AUC(0-tau) Versus eRVR Status   [ Time Frame: Week 4 and Week 12 ]

41.  Secondary:   Correlation of Individual GSK2336805 Dose With Week 4 Plasma Cmax, Ctau, C0 Versus eRVR Status   [ Time Frame: Week 4 and Week 12 ]

42.  Secondary:   Correlation of Individual GSK2336805 Dose With Week 4 Plasma AUC(0-tau) Versus RVR Status   [ Time Frame: Week 4 ]

43.  Secondary:   Correlation of Individual GSK2336805 Dose With Week 4 Plasma Cmax, Ctau, C0 Versus RVR Status   [ Time Frame: Week 4 ]

44.  Secondary:   Correlation of Individual GSK2336805 Dose With Pre-dose Plasma Concentration at Week 4 and Week 12 Versus eRVR Status   [ Time Frame: Week 4 and Week 12 ]

45.  Secondary:   Correlation GSK2336805 Pre-dose Plasma Concentration on Day 2 Versus Reduction in HCV RNA on Day 2   [ Time Frame: Day 2 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
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  More Information
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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:
Protocol contains no citations


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01648140     History of Changes
Other Study ID Numbers: 115879
Study First Received: July 12, 2012
Results First Received: April 25, 2017
Last Updated: April 25, 2017