Last updated: 11/07/2018 09:36:36
Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 With Peginterferon and Ribavirin in Chronic Hepatitis C Subjects
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: Double-Blind, Randomized, Placebo-Controlled Study to Assess Safety, Efficacy, and Pharmacokinetics (PK) of GSK2336805 in Combination With Peginterferon and Ribavirin in Treatment-naive Chronic Hepatitis C Subjects With Hepatitis C Virus Genotypes 1 or 4
Trial description: GSK2336805 is a hepatitis C virus (HCV) NS5A inhibitor being developed for the treatment of chronic hepatitis C (CHC). This study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with chronic hepatitis C (CHC).
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of participant achieving rapid virological response (RVR) at Day 28, Nominal Analysis
Timeframe: Day 28
Number of participant achieving RVR at Day 28, (Primary and Supportive Analyses)
Timeframe: Day 28
Probability of participants with HCV genotype 1 achieving RVR At Day 28, Nominal Analysis
Timeframe: Day 28
Probability of participants with HCV genotype 1 achieving RVR at Day 28, Primary and Supportive Analyses
Timeframe: Day 28
Number of participants with HCV genotype 1 With virologic response
Timeframe: Day 7, 14 and 21
Change from Baseline in HCV viral load during 24 hour (h) following a single dose of GSK2336805 on the log 10 scale
Timeframe: Day 1 (Baseline [Pre-dose], 1, 2, 4, 6, and 8 and 24 h)
Number of participants with any adverse events (AEs) and any serious adverse event (SAE) during treatment period
Timeframe: Up to Day 28
Change from Baseline in QTcF Interval at Day 2 and 28
Timeframe: Baseline (Day 1, Pre-dose ), Day 2 and Day 28
Secondary outcomes:
Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28
Timeframe: Baseline (Day 1) to Day 28
Number of Participants with shift from Baseline to worst post baseline toxicity grade for serum chemistry parameters for Day 1 to Day 28
Timeframe: Baseline (Day 1) and 28
Number of participants with Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
Timeframe: Day 14, 28, Follow-up (Day 42)
Number of participants with vital signs of potential clinical concern
Timeframe: Up to 42 days
Mean serum HCV RNA levels at Baseline (Day 1), Day 2 and Day 28
Timeframe: Baseline (Day 1, pre-dose), Day 2 (24 h, Post-dose) and Day 28
Mean change from Baseline in serum HCV RNA levels at Day 2 and Day 28
Timeframe: Baseline (Day 1, Pre -dose ) and Day 2 (24 h, post-dose), Day 28
Change from Baseline in serum Alanine aminotransferase levels
Timeframe: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42
Median serum alanine aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Timeframe: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42
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
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)
Median time of maximal plasma concentration (Tmax) of GSK2336805 and lag time before first observation of quantifiable concentration (Tlag) at Day 1
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)
Mean maximum plasma concentration of GSK2336805 (Cmax) and concentration at 24 h (C24) at Day 1
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
Mean apparent clearance (CL/F) of GSK2336805
Timeframe: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
Mean pre-dose concentration and concentration at 2 to 4 h post-dose of GSK2336805 at Days 7, 14, 21, and 28
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 28
Interventions:
Drug: GSK2336805
Drug: Pegylated interferon alfa-2a
Drug: Ribavirin
Drug: GSK2336805 Matching Placebo
Enrollment:
16
Observational study model:
Not applicable
Primary completion date:
2011-05-12
Time perspective:
Not applicable
Clinical publications:
Gardner S, Cutrell A, Elko-Simms C, Adkison K, Hamatake R, Walker J, Rodriguez-Torres M, Hong Z.A Double-blind, randomized, placebo-controlled study to assess the safety, antiviral activity and pharmacokinetics of GSK2336805 when given as monotherapy and in combination with peginterferon alfa-2a and ribavirin in hepatitis C virus genotype 1-infected treatment-naive subjects.Liver Int.2014;34(6):e89-e95
Stephen Gardner, Amy Cutrell, Cindy Elko-Simms, Kimbery Adkison, Robert Hamatake, Jill Walker, Maribel Rodriguez-Torres, Zhi Hong. A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 When Given as Monotherapy and in Combination With Peginterferon alfa-2a and Ribavirin in Hepatitis C Virus Genotype 1-infected Treatment-naive Subjects. Liver Int.
Medical condition
Hepatitis C, Chronic
Product
GSK2336805
Collaborators
Pharmaceutical Product Development Clinical Research Organization (CRO)
Study date(s)
July 2011 to December 2011
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 70 years
Accepts healthy volunteers
No
- –Documented chronic genotype 1 or genotype 4 HCV infection
- –Naïve to all HCV antiviral treatment(s)
- –Positive test at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody
- –History of any other clinically significant chronic liver disease
Inclusion and exclusion criteria
Inclusion criteria:
- –Documented chronic genotype 1 or genotype 4 HCV infection –Naïve to all HCV antiviral treatment(s) –Agree to IL28B genotyping –A body mass index >18 kg/m2 but not exceeding 36 kg/m2 –Liver biopsy obtained within 3 years (36 calendar months) prior to the Day 1 visit, with a fibrosis classification of non-cirrhotic. If no recent (<36 months) liver biopsy is available, a study qualifying biopsy must be performed prior to Baseline (Day 1) –All fertile males and females must use two forms of effective contraception between them during treatment and during the 24 weeks after treatment ends –Otherwise healthy as determined by the medical history, physical examination, ECG findings, and clinical laboratory measurements performed at Screening
Exclusion criteria:
- –Positive test at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody –History of any other clinically significant chronic liver disease –History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease –Positive results on urine screen for drugs of abuse test at Screening (unless used as medical treatment, e.g., with a prescription) –History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) –Screening ECG corrected QT interval value greater than 450 ms and/or clinically significant ECG findings –A personal or family history of Torsade de Pointes findings –Pregnant or nursing women –Males with a female partner who is pregnant –Abnormal hematological and biochemical parameters as specified in the protocol –History of major organ transplantation with an existing functional graft –Thyroid dysfunction not adequately controlled –Subjects with a history of suicide attempt or hospitalization for depression in the past 5 years and/or any current (within 6 months) severe or poorly controlled psychiatric disorder –History or current evidence of immunologic disorder; pulmonary, cardiac, or pulmonary disease; seizure disorder; cancer or history of malignancy that in the opinion of the investigator makes the subject unsuitable for the study –Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to first dose administration
Trial location(s)
Location
GSK Investigational Site
Anaheim, California, United States, 92801
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Las Vegas, Nevada, United States, 89109
Status
Study Complete
Location
GSK Investigational Site
Chula Vista, California, United States, 91911
Status
Study Complete
Location
GSK Investigational Site
Coronado, California, United States, 92118
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Houston, Texas, United States, 77004
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Oceanside, California, United States, 92056
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Juan, Puerto Rico, Puerto Rico, 00927
Status
Study Complete
Location
GSK Investigational Site
La Mesa, California, United States, 91942
Status
Study Complete
Location
GSK Investigational Site
Miramar, Florida, United States, 33025
Status
Terminated/Withdrawn
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2011-05-12
Actual study completion date
2011-05-12
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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