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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 201335 as Softgel Capsule in Naive Hepatitis C Virus (HCV) Patients

Primary Purpose

Hepatitis C, Pharmacokinetics

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
ribavirin (RBV)
pegylated interferon (PegIFN) alfa-2a
pegylated interferon (PegIFN) alfa-2a
ribavirin (RBV)
BI 201335 NA low placebo
pegylated interferon (PegIFN) alfa-2a
ribavirin (RBV)
BI 201335 NA high
BI 201335 NA low
BI 201335 NA high placebo
BI 201335 NA high
Placebo
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • chronic HCV genotype-1;
  • high viral load

Exclusion criteria:

  • Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening
  • Previous treatment with protease inhibitor

Sites / Locations

  • 1220.14.003 Boehringer Ingelheim Investigational Site
  • 1220.14.001 Boehringer Ingelheim Investigational Site
  • 1220.14.002 Boehringer Ingelheim Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

BI 201335 NA low TN

BI 201335 NA high TN

BI 201335 NA high TE

Placebo in Treatment Naive (TN) Patients

Arm Description

patient to receive a capsule containing low dose of BI 201335 NA/Drug for treatment-naive (TN) patients

patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-naive (TN )patients

patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-experienced (TE) patients

Outcomes

Primary Outcome Measures

Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy
Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy
Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in triple combination therapy for treatment naive patients and treatment experienced patients.
Assessment of Tolerability in Triple Combination Therapy
An assessment of tolerability for the safety of the triple combination therapy with BI 201335 NA, PegIFN α -2a and RBV.

Secondary Outcome Measures

Week 2 Virological Response (W2VR)
Number of patients satisfying W2VR (plasma HCV RNA (Hepatitis C Virus Ribonucleic acid) level below the limit of quantification (BLQ))
Week 4 Virological Response (W4VR)
Number of patients satisfying W4VR (plasma HCV RNA level below the limit of quantification (BLQ))
Rapid Virological Response (RVR)
Number of patients satisfying RVR (plasma HCV RNA level below the limit of detection (BLD) at Week 4)
Change From Baseline in HCV Viral Load
Change form baseline in HCV viral load (log10) after 4 weeks
Day 28 Virologic Response
Number of patients with HCV viral load reduction >= 2 log10 at Week 4
Early Virological Response (EVR)
Number of patients with reduction >= 2 log10 in plasma HCV RNA level at Week 12
Complete Early Virological Response (cEVR)
Number of patients with plasma HCV RNA level BLD at Week 12
End of Treatment Response (ETR)
Number of patients with plasma HCV RNA level BLD at week 48
Sustained Virologic Response (SVR)
Number of patients with plasma HCV RNA level BLD 24 weeks after treatment completion
Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV
Drug-related AEs in SOC treatment period were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV
Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in SOC period for treatment naive patients and treatment experienced patients.
Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV
An assessment of tolerability for the safety of the SOC with PegIFN alfa-2a and RBV.
AUCτ,1 for BI 201335 ZW
Area under the curve (AUC) concentration after the first dose of BI 201335 ZW
Cmax of BI 201335 ZW
Maximum concentration of BI 201335 ZW after multiple oral admin. of BI 201335 NA with RBV and PegIFN alfa-2a
AUCτ,ss of BI 201335 ZW
AUC at steady state after 4 weeks combination of the last dose
Cmax,ss of BI 201335 ZW
Maximum concentration of BI 201335 ZW at steady state
AUCτ,1 for Ribavirin (RBV)
Area under the plasma concentration curve of RBV after the first dose of placebo or BI 201335 NA with with RBV and PegIFN alfa-2a
Cmax of RBV
Maximum Plasma concentration of RBV after multiple oral admin. of placebo with RBV and PegIFN alfa-2a
AUCτ,ss of RBV
Area under the plasma concentration curve of RBV after the multiple oral administration of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state
Cmax,ss of RBV
Maximum Plasma concentration of RBV after multiple oral admin. of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state
Tmax for BI 201335 ZW
Time to maximum plasma concentration (tmax) of BI 201335 ZW after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a
Tmax for RBV
Time to maximum plasma concentration (tmax) of RBV after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a
Tmax, ss for BI 201335 ZW
Time from last dosing to the maximum plasma concentration (tmax) of BI 201335 ZW after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state
Tmax, ss for RBV
Time to the maximum plasma concentration (tmax) of RBV after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state
t1/2,ss for BI 201335 ZW
terminal half-life of the analyte in plasma at steady state (t1/2,ss)
Cmin,ss for BI 201335 ZW
Minimum concentration of the analyte (BI 201335 ZW) in plasma over the dosing interval at steady state
Cmin,ss for RBV
Minimum concentration of the analyte (RBV) in plasma over the dosing interval at steady state
Cavg for BI 201335 ZW
average plasma concentration (Cavg) of BI 201335 ZW
Cavg for RBV
average plasma concentration (Cavg) of RBV
CL/F,ss for BI 201335 ZW
apparent clearance of the analyte (BI 201335 ZW) in plasma at steady state (CL/F,ss) following multiple oral administration

Full Information

First Posted
July 21, 2009
Last Updated
July 3, 2015
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT00947349
Brief Title
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 201335 as Softgel Capsule in Naive Hepatitis C Virus (HCV) Patients
Official Title
Safety, Pharmacokinetics and Antiviral Effect of BI 201335 NA in HCV-1 Infected Patients Treated for 28 Days for Treatment naïve and Experienced Patients Treated in Combination With Peg Interferon Alfa-2a and Ribavirin
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary
The current Standard of Care (SOC) for chronic HCV infection, which is pegylated interferon-alfa as combination therapy with ribavirin for 24-48 weeks of treatment, is effective in only part of the patients and is often associated with severe adverse effects leading to discontinuation of treatment and dose modifications. A number of compounds with direct activity are currently under clinical development, incl. BI 201335. BI 201335 works by preventing the Hepatitis C virus from replicating by binding to the HCV protease (enzyme). The main purpose of this clinical trial with BI 201335 is to see how well BI 201335 works and how safe BI 201335 is to use daily in combination with PegIFN and RBV in HCV infected patients

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Pharmacokinetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BI 201335 NA low TN
Arm Type
Experimental
Arm Description
patient to receive a capsule containing low dose of BI 201335 NA/Drug for treatment-naive (TN) patients
Arm Title
BI 201335 NA high TN
Arm Type
Experimental
Arm Description
patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-naive (TN )patients
Arm Title
BI 201335 NA high TE
Arm Type
Experimental
Arm Description
patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-experienced (TE) patients
Arm Title
Placebo in Treatment Naive (TN) Patients
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ribavirin (RBV)
Intervention Description
ribavirin (RBV)
Intervention Type
Drug
Intervention Name(s)
pegylated interferon (PegIFN) alfa-2a
Intervention Description
pegylated interferon (PegIFN) alfa-2a
Intervention Type
Drug
Intervention Name(s)
pegylated interferon (PegIFN) alfa-2a
Intervention Description
pegylated interferon (PegIFN) alfa-2a
Intervention Type
Drug
Intervention Name(s)
ribavirin (RBV)
Intervention Description
ribavirin (RBV)
Intervention Type
Drug
Intervention Name(s)
BI 201335 NA low placebo
Intervention Description
Placebo
Intervention Type
Drug
Intervention Name(s)
pegylated interferon (PegIFN) alfa-2a
Intervention Description
pegylated interferon (PegIFN) alfa-2a
Intervention Type
Drug
Intervention Name(s)
ribavirin (RBV)
Intervention Description
ribavirin (RBV)
Intervention Type
Drug
Intervention Name(s)
BI 201335 NA high
Intervention Description
BI 201335 NA high
Intervention Type
Drug
Intervention Name(s)
BI 201335 NA low
Intervention Description
BI 201335 NA
Intervention Type
Drug
Intervention Name(s)
BI 201335 NA high placebo
Intervention Description
placebo
Intervention Type
Drug
Intervention Name(s)
BI 201335 NA high
Intervention Description
BI 201335 NA high
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy
Description
Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.
Time Frame
4 weeks
Title
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy
Description
Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in triple combination therapy for treatment naive patients and treatment experienced patients.
Time Frame
4 weeks
Title
Assessment of Tolerability in Triple Combination Therapy
Description
An assessment of tolerability for the safety of the triple combination therapy with BI 201335 NA, PegIFN α -2a and RBV.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Week 2 Virological Response (W2VR)
Description
Number of patients satisfying W2VR (plasma HCV RNA (Hepatitis C Virus Ribonucleic acid) level below the limit of quantification (BLQ))
Time Frame
2 weeks
Title
Week 4 Virological Response (W4VR)
Description
Number of patients satisfying W4VR (plasma HCV RNA level below the limit of quantification (BLQ))
Time Frame
4 weeks
Title
Rapid Virological Response (RVR)
Description
Number of patients satisfying RVR (plasma HCV RNA level below the limit of detection (BLD) at Week 4)
Time Frame
4 weeks
Title
Change From Baseline in HCV Viral Load
Description
Change form baseline in HCV viral load (log10) after 4 weeks
Time Frame
baseline and week 4
Title
Day 28 Virologic Response
Description
Number of patients with HCV viral load reduction >= 2 log10 at Week 4
Time Frame
4 weeks
Title
Early Virological Response (EVR)
Description
Number of patients with reduction >= 2 log10 in plasma HCV RNA level at Week 12
Time Frame
12 Weeks
Title
Complete Early Virological Response (cEVR)
Description
Number of patients with plasma HCV RNA level BLD at Week 12
Time Frame
12 weeks
Title
End of Treatment Response (ETR)
Description
Number of patients with plasma HCV RNA level BLD at week 48
Time Frame
48 weeks
Title
Sustained Virologic Response (SVR)
Description
Number of patients with plasma HCV RNA level BLD 24 weeks after treatment completion
Time Frame
72 weeks
Title
Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV
Description
Drug-related AEs in SOC treatment period were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.
Time Frame
44 weeks
Title
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV
Description
Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in SOC period for treatment naive patients and treatment experienced patients.
Time Frame
44 weeks
Title
Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV
Description
An assessment of tolerability for the safety of the SOC with PegIFN alfa-2a and RBV.
Time Frame
44 weeks
Title
AUCτ,1 for BI 201335 ZW
Description
Area under the curve (AUC) concentration after the first dose of BI 201335 ZW
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
Title
Cmax of BI 201335 ZW
Description
Maximum concentration of BI 201335 ZW after multiple oral admin. of BI 201335 NA with RBV and PegIFN alfa-2a
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
Title
AUCτ,ss of BI 201335 ZW
Description
AUC at steady state after 4 weeks combination of the last dose
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Title
Cmax,ss of BI 201335 ZW
Description
Maximum concentration of BI 201335 ZW at steady state
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Title
AUCτ,1 for Ribavirin (RBV)
Description
Area under the plasma concentration curve of RBV after the first dose of placebo or BI 201335 NA with with RBV and PegIFN alfa-2a
Time Frame
-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose
Title
Cmax of RBV
Description
Maximum Plasma concentration of RBV after multiple oral admin. of placebo with RBV and PegIFN alfa-2a
Time Frame
-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose
Title
AUCτ,ss of RBV
Description
Area under the plasma concentration curve of RBV after the multiple oral administration of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state
Time Frame
-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose
Title
Cmax,ss of RBV
Description
Maximum Plasma concentration of RBV after multiple oral admin. of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state
Time Frame
-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose
Title
Tmax for BI 201335 ZW
Description
Time to maximum plasma concentration (tmax) of BI 201335 ZW after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
Title
Tmax for RBV
Description
Time to maximum plasma concentration (tmax) of RBV after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose
Title
Tmax, ss for BI 201335 ZW
Description
Time from last dosing to the maximum plasma concentration (tmax) of BI 201335 ZW after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Title
Tmax, ss for RBV
Description
Time to the maximum plasma concentration (tmax) of RBV after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Title
t1/2,ss for BI 201335 ZW
Description
terminal half-life of the analyte in plasma at steady state (t1/2,ss)
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Title
Cmin,ss for BI 201335 ZW
Description
Minimum concentration of the analyte (BI 201335 ZW) in plasma over the dosing interval at steady state
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Title
Cmin,ss for RBV
Description
Minimum concentration of the analyte (RBV) in plasma over the dosing interval at steady state
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Title
Cavg for BI 201335 ZW
Description
average plasma concentration (Cavg) of BI 201335 ZW
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Title
Cavg for RBV
Description
average plasma concentration (Cavg) of RBV
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose
Title
CL/F,ss for BI 201335 ZW
Description
apparent clearance of the analyte (BI 201335 ZW) in plasma at steady state (CL/F,ss) following multiple oral administration
Time Frame
10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose

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 HCV genotype-1; high viral load Exclusion criteria: Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening Previous treatment with protease inhibitor
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
1220.14.003 Boehringer Ingelheim Investigational Site
City
Kurashiki, Okayama
Country
Japan
Facility Name
1220.14.001 Boehringer Ingelheim Investigational Site
City
Minato-ku, Tokyo
Country
Japan
Facility Name
1220.14.002 Boehringer Ingelheim Investigational Site
City
Nishinomiya, Hyogo
Country
Japan

12. IPD Sharing Statement

Links:
URL
http://trials.boehringer-ingelheim.com/
Description
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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 201335 as Softgel Capsule in Naive Hepatitis C Virus (HCV) Patients

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