This Trial Evaluates Safety, Pharmacokinetic Profile and Anti-viral Response of BI 207127 and BI 201335 for Patients With Chronic Hepatitis C
Primary Purpose
Hepatitis C, Chronic
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
BI 207127 NA
peginterferon
Ribavirin
Ribavirin
BI 207127 NA
BI 201335 NA
BI 201335 NA
peginterferon
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic
Eligibility Criteria
Inclusion criteria:
Chronic hepatitis C, diagnosed by positive anti-hepatitis C virus(HCV) antibodies and detected HCV ribonucleic acid(RNA) at screening in addition to:
- positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening; or,
- liver biopsy consistent with chronic HCV infection.
- HCV infection of genotype 1 confirmed by genotypic testing at screening
- Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection.
- Plasma HCV RNA = 100,000 IU/mL at screening
Exclusion criteria:
- Hepatitis C infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening
- Human immunodeficiency virus (HIV) co-infection
- Decompensated liver disease, or history of decompensated liver disease
- Body weight < 40 or > 125 kg at screening
- Hemoglobin <12.0g/dL for women and <13.0g/dL for men at screening
- White blood cell count <3000 cells/mm3 at screening
- Absolute neutrophil count < 1,500 cells/mm3 at screening
- Platelet count < 90,000 /mm3 at screening
- Serum creatinine > 1.5xUpper Limit of Normal range(ULN) or creatinine clearance =50 mL/min at screening
Sites / Locations
- 1241.25.002 Boehringer Ingelheim Investigational Site
- 1241.25.005 Boehringer Ingelheim Investigational Site
- 1241.25.003 Boehringer Ingelheim Investigational Site
- 1241.25.004 Boehringer Ingelheim Investigational Site
- 1241.25.001 Boehringer Ingelheim Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
BI 207127 NA, BI 201335 NA(high dose), R
BI 207127 NA,BI 201335 NA(low dose),RBV
Arm Description
Patients receive BI 207127 NA,BI 201335 NA(high dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
Patients receive BI 207127 NA,BI 201335 NA(low dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
Outcomes
Primary Outcome Measures
Number of Patients With Drug-related Adverse Events
Number of patients with investigator defined drug-related Adverse Events
Secondary Outcome Measures
Percentage of Participants With Virological Response at Week 4
Percentage of participants with plasma HCV RNA (hepatitis C virus (HCV) ribonucleic acid (RNA)) level <25 IU/mL (undetected or detected) at week 4.
Percentage of Participants With Virological Response at Week 8
Percentage of participants with plasma HCV RNA (hepatitis C virus ribonucleic acid ) level <25 IU/mL (undetected or detected) at week 8.
Maximum Measured Concentration (Cmax) of Deleobuvir
Maximum measured concentration of BI 207127 (Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir
Time from last dosing to the maximum concentration of Deleobuvir (BI 207127) in plasma after the morning dose of Nth day (Tmax,N).
Area Under the Curve (AUC) of Deleobuvir
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Maximum Measured Concentration (Cmax) of Faldaprevir
Maximum measured concentration of Faldaprevir (BI 201335 ZW) in plasma following the morning dose of Nth day (Cmax,N).
Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir
Time from last dosing to the maximum concentration of Faldaprevir (BI 201335 ZW) in plasma after the morning dose of Nth day (Tmax,N).
Area Under the Curve (AUC) of Faldaprevir
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Maximum Measured Concentration (Cmax) of BI 208333
Maximum measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333
Time from last dosing to the maximum concentration of BI 208333 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).
Area Under the Curve (AUC) of BI 208333
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Maximum Measured Concentration (Cmax) of CD 6168
Maximum measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168
Time from last dosing to the maximum concentration of CD 6168 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).
Area Under the Curve (AUC) of CD 6168
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Maximum Measured Concentration (Cmax) of CD 6168-AG
Maximum measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). AG=acylglucuronide.
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG
Time from last dosing to the maximum concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N). AG=acylglucuronide.
Area Under the Curve (AUC) of CD 6168-AG
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. AG=acylglucuronide.
Maximum Measured Concentration (Cmax) of RBV
Maximum measured concentration of ribavirin (RBV) in plasma following the morning dose of Nth day (Cmax,N).
Time From Last Dosing to the Maximum Concentration (Tmax) of RBV
Time from last dosing to the maximum concentration of ribavirin (RBV) in plasma after the morning dose of Nth day (Tmax,N).
Area Under the Curve (AUC) of RBV
Area under the concentration time curve (AUC) of ribavirin (RBV) in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir
Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of Deleobuvir versus itself (RA,Cmax,Met,ss).
AUC Accumulation Ratio of Deleobuvir
Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of Deleobuvir versus itself (RA,AUC,Met,ss).
Mean Residence Time (MRTpo,ss) of Deleobuvir
Mean residence time of BI 207127 (Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).
Apparent Clearance (CL/F,ss) of Deleobuvir
Apparent clearance of BI 207127 (Deleobuvir) in plasma following extravascular administration on the 57th day (CL/F,ss).
Predose Measured Concentration of Deleobuvir
Predose measured concentration of BI 207127 (Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir
Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N).
AUC Accumulation Ratio of Faldaprevir
Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N).
Mean Residence Time (MRTpo,ss) of Faldaprevir
Mean residence time of Faldaprevir (BI 201335 ZW) in the body after oral administration at steady state (MRTpo,ss).
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Apparent Clearance (CL/F,ss) of Faldaprevir
Apparent clearance of Faldaprevir (BI 201335 ZW) in plasma following extravascular administration on the 57th day (CL/F,ss).
Predose Measured Concentration of Faldaprevir
Predose measured concentration of Faldaprevir (BI 201335 ZW) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Cmax Accumulation Ratio of BI 208333
Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of BI 208333 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).
AUC Accumulation Ratio of BI 208333
Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of BI 208333 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).
Mean Residence Time (MRTpo,ss) of BI 208333
Mean residence time of BI 208333 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Predose Measured Concentration of BI 208333
Predose measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Cmax Accumulation Ratio of CD 6168
Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).
AUC Accumulation Ratio of CD 6168
Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).
Mean Residence Time (MRTpo,ss) of CD 6168
Mean residence time of CD 6168 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Predose Measured Concentration of CD 6168
Predose measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Cmax Accumulation Ratio of CD 6168-AG
Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168-AG versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss). AG=acylglucuronide.
AUC Accumulation Ratio of CD 6168-AG
Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168-AG versus AUC,ss of Deleobuvir (RA,AUC,Met,ss). AG=acylglucuronide.
Mean Residence Time (MRTpo,ss) of CD 6168-AG
Mean residence time of CD 6168-AG (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). AG=acylglucuronide.
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Predose Measured Concentration of CD 6168-AG
Predose measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). AG=acylglucuronide.
AUC Accumulation Ratio of RBV
Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the 57th day and after the first dose (RA,AUC,57).
Cmax Accumulation Ratio (RA,Cmax,57) of RBV
Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the 57th day and after the first dose (RA,Cmax,57).
Mean Residence Time (MRTpo,ss) of RBV
Mean residence time of ribavirin (RBV) in the body after oral administration at steady state (MRTpo,ss).
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Predose Measured Concentration of RBV
Predose measured concentration of ribavirin (RBV) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01528735
Brief Title
This Trial Evaluates Safety, Pharmacokinetic Profile and Anti-viral Response of BI 207127 and BI 201335 for Patients With Chronic Hepatitis C
Official Title
An Open-label, Ascending Dose, Phase II Study to Evaluate Tolerability, Safety, Antiviral Activity, and Pharmacokinetics of BI 207127 NA in Combination With BI 201335 NA and Ribavirin for 8 Weeks in Treatment-naïve Japanese Patients With Genotype 1chronic Hepatitis C Virus Infection
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
The objective of this trial is to investigate tolerability, safety, pharmacokinetics and antiviral activity of BI 207127 NA in combination with BI 201335 NA and ribavirin for 8 weeks in Japanese treatment-naive patients with chronic GT-1 HCV infection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BI 207127 NA, BI 201335 NA(high dose), R
Arm Type
Experimental
Arm Description
Patients receive BI 207127 NA,BI 201335 NA(high dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
Arm Title
BI 207127 NA,BI 201335 NA(low dose),RBV
Arm Type
Experimental
Arm Description
Patients receive BI 207127 NA,BI 201335 NA(low dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
Intervention Type
Drug
Intervention Name(s)
BI 207127 NA
Intervention Description
one fix dose
Intervention Type
Drug
Intervention Name(s)
peginterferon
Intervention Description
per package insert
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
per weight BID
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
per weight BID
Intervention Type
Drug
Intervention Name(s)
BI 207127 NA
Intervention Description
one fix dose
Intervention Type
Drug
Intervention Name(s)
BI 201335 NA
Intervention Description
high dose
Intervention Type
Drug
Intervention Name(s)
BI 201335 NA
Intervention Description
low dose
Intervention Type
Drug
Intervention Name(s)
peginterferon
Intervention Description
per package insert
Primary Outcome Measure Information:
Title
Number of Patients With Drug-related Adverse Events
Description
Number of patients with investigator defined drug-related Adverse Events
Time Frame
From first dose of study medication until 30 days after last dose of study medication, up to 199 days
Secondary Outcome Measure Information:
Title
Percentage of Participants With Virological Response at Week 4
Description
Percentage of participants with plasma HCV RNA (hepatitis C virus (HCV) ribonucleic acid (RNA)) level <25 IU/mL (undetected or detected) at week 4.
Time Frame
4 weeks
Title
Percentage of Participants With Virological Response at Week 8
Description
Percentage of participants with plasma HCV RNA (hepatitis C virus ribonucleic acid ) level <25 IU/mL (undetected or detected) at week 8.
Time Frame
8 weeks
Title
Maximum Measured Concentration (Cmax) of Deleobuvir
Description
Maximum measured concentration of BI 207127 (Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir
Description
Time from last dosing to the maximum concentration of Deleobuvir (BI 207127) in plasma after the morning dose of Nth day (Tmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Area Under the Curve (AUC) of Deleobuvir
Description
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Maximum Measured Concentration (Cmax) of Faldaprevir
Description
Maximum measured concentration of Faldaprevir (BI 201335 ZW) in plasma following the morning dose of Nth day (Cmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir
Description
Time from last dosing to the maximum concentration of Faldaprevir (BI 201335 ZW) in plasma after the morning dose of Nth day (Tmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Area Under the Curve (AUC) of Faldaprevir
Description
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Maximum Measured Concentration (Cmax) of BI 208333
Description
Maximum measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333
Description
Time from last dosing to the maximum concentration of BI 208333 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Area Under the Curve (AUC) of BI 208333
Description
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Maximum Measured Concentration (Cmax) of CD 6168
Description
Maximum measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Title
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168
Description
Time from last dosing to the maximum concentration of CD 6168 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Area Under the Curve (AUC) of CD 6168
Description
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Maximum Measured Concentration (Cmax) of CD 6168-AG
Description
Maximum measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). AG=acylglucuronide.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Title
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG
Description
Time from last dosing to the maximum concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N). AG=acylglucuronide.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Area Under the Curve (AUC) of CD 6168-AG
Description
Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. AG=acylglucuronide.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Maximum Measured Concentration (Cmax) of RBV
Description
Maximum measured concentration of ribavirin (RBV) in plasma following the morning dose of Nth day (Cmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Title
Time From Last Dosing to the Maximum Concentration (Tmax) of RBV
Description
Time from last dosing to the maximum concentration of ribavirin (RBV) in plasma after the morning dose of Nth day (Tmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Title
Area Under the Curve (AUC) of RBV
Description
Area under the concentration time curve (AUC) of ribavirin (RBV) in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Title
Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir
Description
Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of Deleobuvir versus itself (RA,Cmax,Met,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
AUC Accumulation Ratio of Deleobuvir
Description
Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of Deleobuvir versus itself (RA,AUC,Met,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Mean Residence Time (MRTpo,ss) of Deleobuvir
Description
Mean residence time of BI 207127 (Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Title
Apparent Clearance (CL/F,ss) of Deleobuvir
Description
Apparent clearance of BI 207127 (Deleobuvir) in plasma following extravascular administration on the 57th day (CL/F,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Title
Predose Measured Concentration of Deleobuvir
Description
Predose measured concentration of BI 207127 (Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57
Title
Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir
Description
Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
AUC Accumulation Ratio of Faldaprevir
Description
Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Mean Residence Time (MRTpo,ss) of Faldaprevir
Description
Mean residence time of Faldaprevir (BI 201335 ZW) in the body after oral administration at steady state (MRTpo,ss).
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Title
Apparent Clearance (CL/F,ss) of Faldaprevir
Description
Apparent clearance of Faldaprevir (BI 201335 ZW) in plasma following extravascular administration on the 57th day (CL/F,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Title
Predose Measured Concentration of Faldaprevir
Description
Predose measured concentration of Faldaprevir (BI 201335 ZW) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57
Title
Cmax Accumulation Ratio of BI 208333
Description
Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of BI 208333 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
AUC Accumulation Ratio of BI 208333
Description
Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of BI 208333 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57
Title
Mean Residence Time (MRTpo,ss) of BI 208333
Description
Mean residence time of BI 208333 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57
Title
Predose Measured Concentration of BI 208333
Description
Predose measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57
Title
Cmax Accumulation Ratio of CD 6168
Description
Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Title
AUC Accumulation Ratio of CD 6168
Description
Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Title
Mean Residence Time (MRTpo,ss) of CD 6168
Description
Mean residence time of CD 6168 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57
Title
Predose Measured Concentration of CD 6168
Description
Predose measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57
Title
Cmax Accumulation Ratio of CD 6168-AG
Description
Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168-AG versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss). AG=acylglucuronide.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Title
AUC Accumulation Ratio of CD 6168-AG
Description
Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168-AG versus AUC,ss of Deleobuvir (RA,AUC,Met,ss). AG=acylglucuronide.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57
Title
Mean Residence Time (MRTpo,ss) of CD 6168-AG
Description
Mean residence time of CD 6168-AG (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). AG=acylglucuronide.
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57
Title
Predose Measured Concentration of CD 6168-AG
Description
Predose measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). AG=acylglucuronide.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57
Title
AUC Accumulation Ratio of RBV
Description
Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the 57th day and after the first dose (RA,AUC,57).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Title
Cmax Accumulation Ratio (RA,Cmax,57) of RBV
Description
Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the 57th day and after the first dose (RA,Cmax,57).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57
Title
Mean Residence Time (MRTpo,ss) of RBV
Description
Mean residence time of ribavirin (RBV) in the body after oral administration at steady state (MRTpo,ss).
This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on day 57
Title
Predose Measured Concentration of RBV
Description
Predose measured concentration of ribavirin (RBV) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).
Time Frame
10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 11 and 57
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Chronic hepatitis C, diagnosed by positive anti-hepatitis C virus(HCV) antibodies and detected HCV ribonucleic acid(RNA) at screening in addition to:
positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening; or,
liver biopsy consistent with chronic HCV infection.
HCV infection of genotype 1 confirmed by genotypic testing at screening
Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection.
Plasma HCV RNA = 100,000 IU/mL at screening
Exclusion criteria:
Hepatitis C infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening
Human immunodeficiency virus (HIV) co-infection
Decompensated liver disease, or history of decompensated liver disease
Body weight < 40 or > 125 kg at screening
Hemoglobin <12.0g/dL for women and <13.0g/dL for men at screening
White blood cell count <3000 cells/mm3 at screening
Absolute neutrophil count < 1,500 cells/mm3 at screening
Platelet count < 90,000 /mm3 at screening
Serum creatinine > 1.5xUpper Limit of Normal range(ULN) or creatinine clearance =50 mL/min at screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1241.25.002 Boehringer Ingelheim Investigational Site
City
Kofu, Yamanashi
Country
Japan
Facility Name
1241.25.005 Boehringer Ingelheim Investigational Site
City
Kurashiki, Okayama
Country
Japan
Facility Name
1241.25.003 Boehringer Ingelheim Investigational Site
City
Nagoya, Aichi
Country
Japan
Facility Name
1241.25.004 Boehringer Ingelheim Investigational Site
City
Nishinomiya, Hyogo
Country
Japan
Facility Name
1241.25.001 Boehringer Ingelheim Investigational Site
City
Omura, Nagasaki
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
25991083
Citation
Yatsuhashi H, Kodani N, Ugai H, Omata M. Open-label phase 2 study of faldaprevir, deleobuvir and ribavirin in Japanese treatment-naive patients with chronic hepatitis C virus genotype 1 infection. Hepatol Res. 2016 Mar;46(3):E189-93. doi: 10.1111/hepr.12535. Epub 2015 Jun 18.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/
Description
Related Info
Learn more about this trial
This Trial Evaluates Safety, Pharmacokinetic Profile and Anti-viral Response of BI 207127 and BI 201335 for Patients With Chronic Hepatitis C
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