Safety, Antiviral Activity and PK of MRD of BI 201335 in Chronic Hepatitis C Patients Both Treatment Naive and -Experienced
- Conditions
- Hepatitis C, Chronic
- Interventions
- Drug: BI201335Drug: Placebo
- Registration Number
- NCT00793793
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
This study will investigate safety, antiviral activity, and pharmacokinetics of BI 201335 NA in HCV genotype 1 infected patients treated for 14 days monotherapy followed by BI 201335 NA combination therapy with PegIFN/RBV for an additional 14 days for treatment-naïve patients; or for 28 days as BI 201335 NA combination therapy with PegIFN/RBV for treatment-experienced patients.
A secondary objective is to investigate antiviral activity, potential drug-drug interactions and safety of combination therapy of BI 201335 NA and PegIFN/RBV up to 28 days for treatment-naïve patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 96
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 48mg BI201335 patient to receive 48mg solution BI201335 qd +/- PegIFN/RBV fore 28 days Placebo Placebo - 240mg BI201335 patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days 20mg BI201335 patient to receive 20mg solution BI201335 qd +/- PegIFN/RBV fore 28 days 120mg BI201335 patient to receive 120mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
- Primary Outcome Measures
Name Time Method Efficacy: VR (Virologic Response) of >=2 log10 Reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Any Time up to Day 14 (naïve Patients) or Day 28 (Experienced Patients) Baseline and up to 4 weeks Efficacy endpoint: VR (virologic response) of \>=2 log10 reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) from baseline at any time up to Day 14 (naïve patients) or Day 28 (experienced patients).
Occurrence of Adverse Events (AEs) During BI201335 + Washout Period from day 1 and up to 4 weeks + 4 days washout Occurrence of Adverse Events (AEs) during BI201335 + washout period. For placebo patients include all AEs through 30 days after trial discontinuation.
Occurrence of Serious Adverse Events (SAEs) During BI201335 + Washout Period from day 1 and up to 4 weeks + 4 days washout Occurrence of Serious Adverse Events (SAEs)during BI201335 or BI201335+ washout period. For placebo patients include all SAEs through 30 days after trial discontinuation.
Occurrence of Laboratory Test Abnormalities and With Respect to Division of AIDS (DAIDS) Classification and Laboratory Test Values Change Over Time Baseline and up to 4 weeks Occurrence of laboratory test abnormalities and with respect to Division of AIDS (DAIDS) classification and laboratory test values change over time.
ALT=Alanine transaminase (SGPT), AST=Aspartate transaminase (SGOT).
- Secondary Outcome Measures
Name Time Method PK Parameter at Steady State After the Last Dose: Tmax,ss (Time From Last Dosing to the Maximum Measured Concentration of the Analyte in Plasma at Steady State ) Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28) PK parameter at steady state after the last dose: tmax,ss (Time from last dosing to the maximum measured concentration of the analyte in plasma at steady state ).
Rapid Virologic Response (RVR) week 4 Rapid virologic response (RVR): Plasma HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) on Day 28 for all patients.
Sustained Virologic Response (SVR) week 72 Sustained Virologic Response (SVR): Plasma HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at week 72 (Day 504).
PK (Pharmacokinetic) Parameter After the First Dose: Cmax ( Maximum Measured Concentration of the Analyte in Plasma) Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1) PK (pharmacokinetic) parameter after the first dose: Cmax ( Maximum measured concentration of the analyte in plasma ).
.PK Parameter After the First Dose: AUCτ,1 (Area Under the Concentration-time Curve of the Analyte in Plasma Over a Uniform Dosing Interval τ on Day 1) Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1) PK parameter after the first dose: AUCτ,1 (Area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ on day 1).
PK Parameter at Steady State After the Last Dose: t1/2,ss (Terminal Half-life of the Analyte in Plasma at Steady State ) Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28) PK parameter at steady state after the last dose: t1/2,ss (Terminal half-life of the analyte in plasma at steady state \[h\] )
Change From Baseline in Viral Load on Day 14 for Treatment-naïve Patients and on Day 28 Treatment for Treatment-experienced Patients Baseline and up to 4 weeks Change from baseline in viral load on Day 14 for treatment-naïve patients and on Day 28 treatment for treatment-experienced patients.
Early Virologic Response (EVR) week 12 Early Virologic Response (EVR): \>=2 log10 reduction in plasma HCV RNA level from baseline at week 12 (day 84)
Complete EVR1 (cEVR1) week 4 and week 12 VL (Viral load) below the limit of quantification of the Roche COBAS Taqman HCV/HPS assay (25 IU/mL) at 4 weeks and below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at 12 weeks
Complete EVR2 (cEVR2) week 4 and week 12 VL below the limit of detection at both 4 weeks and 12 weeks
Achievement of an HCV RNA Level Below the Limit of Detection Over Time from day 1 and up to 4 weeks Achievement of an HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) over time
Maximum Viral Load Reduction From Baseline up to Day 14 for Treatment-naïve Patients and Day 28 Treatment for Treatment-experienced Patients Baseline and up to 4 weeks Maximum viral load reduction from baseline up to Day 14 for treatment-naïve patients and Day 28 treatment for treatment-experienced patients.
Achievement of an HCV RNA Level Below the Limit of Quantification Over Time from day 1 and up to 4 weeks Achievement of an HCV RNA Level Below the Limit of quantification of the Roche COBAS Taqman HCV/HPS assay (25 IU/mL) Over Time
Achievement of a >= 2 log10 Reduction in Plasma HCV RNA Level From Baseline Over Time from day 1 and up to 4 weeks Achievement of a \>= 2 log10 reduction in plasma HCV RNA level from baseline over time.
Occurrence of Discontinuations Due to AEs During BI201335 or BI201335+PegIFN/RBV Combination Treatment Period from day 1 and up to 4 weeks Occurrence of discontinuations due to AEs during BI201335 or BI201335+PegIFN/RBV combination treatment period.
PK Parameter at Steady State After the Last Dose: MRTpo,ss (Mean Residence Time of the Analyte in the Body at Steady State After Oral Administration) Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28) PK parameter at steady state after the last dose: MRTpo,ss (Mean residence time of the analyte in the body at steady state after oral administration \[h\] )
PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): AUCτ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ ) Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to administration of trial medication in the morning of Day 14 (on day 14) PK parameter for drug-drug interaction (naïve patients with ≥1 log reduction on Day 10): AUCτ,ss ( Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ ).
Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAcmax Day 1, Day 14, and Day 28 For TN patients, comparing exposure on Day 14 to the first dose on Day 1; for TE patients, comparing exposure on Day 28 to the first dose on Day 1.
PK Parameter After the First Dose: Tmax (Time From (Last) Dosing to the Maximum Measured Concentration of the Analyte in Plasma) Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1) PK parameter after the first dose: tmax (Time from (last) dosing to the maximum measured concentration of the analyte in plasma).
PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): Cmax,ss Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to administration of trial medication in the morning of Day 14 (on day 14) PK parameter for drug-drug interaction (naïve patients with ≥1 log reduction on Day 10): Cmax,ss.
PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): Cmin, ss Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to administration of trial medication in the morning of Day 14 (on day 14) PK parameter for drug-drug interaction (naïve patients with ≥1 log reduction on Day 10): Cmin, ss.
PK Parameter at Steady State After the Last Dose: Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ) Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28) PK parameter at steady state after the last dose: Cmax,ss (Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ).
PK Parameter at Steady State After the Last Dose: Cmin,ss (Minimum Measured Concentration of the Analyte in Plasma) Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28) PK parameter at steady state after the last dose: Cmin,ss (Minimum measured concentration of the analyte in plasma).
Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAauc Day 1, Day 14, and Day 28 For TN patients, comparing exposure on Day 14 to the first dose on Day 1; for TE patients, comparing exposure on Day 28 to the first dose on Day 1.
PK Parameter at Steady State After the Last Dose: AUCτ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ) Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28) PK parameter at steady state after the last dose: AUCτ,ss ((Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ).
PK Parameter at Steady State After the Last Dose: CL/F,ss (Apparent Clearance of the Analyte in Plasma at Steady State Following Multiple Oral Dose Administration ) Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28) PK parameter at steady state after the last dose (if applicable): CL/F,ss (ss Apparent clearance of the analyte in plasma at steady state following multiple oral dose administration \[mL/min\] )
PK Parameter at Steady State After the Last Dose: Vz/F,ss (Apparent Volume of Distribution During the Terminal Phase z at Steady State Following an Oral Administration ) Times of -0:05, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, 16:00, 24:00 h relative to last administration of trial medication (on day 28) PK parameter at steady state after the last dose: Vz/F,ss (Apparent volume of distribution during the terminal phase z at steady state following an oral administration \[L\] )
End of Treatment Response (ETR) week 48 End of Treatment Response (ETR): Plasma HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at week 48 (Day 336).
Occurrence of AEs, by Action Taken With Regard to Study Medication from day 1 and up to 4 weeks Occurrence of AEs, by action taken with regard to study medication.
Trial Locations
- Locations (16)
1220.2.10 Boehringer Ingelheim Investigational Site
🇺🇸San Francisco, California, United States
1220.2.15 Boehringer Ingelheim Investigational Site
🇺🇸San Francisco, California, United States
1220.2.17 Boehringer Ingelheim Investigational Site
🇺🇸Baltimore, Maryland, United States
1220.2.11 Boehringer Ingelheim Investigational Site
🇺🇸New York, New York, United States
1220.2.12 Boehringer Ingelheim Investigational Site
🇺🇸New York, New York, United States
1220.2.14 Boehringer Ingelheim Investigational Site
🇺🇸Austin, Texas, United States
1220.2.3304A Boehringer Ingelheim Investigational Site
🇫🇷Lyon, France
1220.2.3303A Boehringer Ingelheim Investigational Site
🇫🇷Marseille, France
1220.2.3301A Boehringer Ingelheim Investigational Site
🇫🇷Paris, France
1220.2.3302A Boehringer Ingelheim Investigational Site
🇫🇷Paris, France
1220.2.49002 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1220.2.49005 Boehringer Ingelheim Investigational Site
🇩🇪Düsseldorf, Germany
1220.2.49004 Boehringer Ingelheim Investigational Site
🇩🇪Kiel, Germany
1220.2.49003 Boehringer Ingelheim Investigational Site
🇩🇪Mainz, Germany
1220.2.34001 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1220.2.49006 Boehringer Ingelheim Investigational Site
🇩🇪Hannover, Germany