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4 Week Combination of BI 207127 NA With Peg-IFN and Ribavirin in Chronic HCV Patients

Primary Purpose

Hepatitis C, Chronic

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BI 207127 middle dose +SOC
BI 207127 high dose+SOC
Placebo + SOC
BI 207127 low dose + SOC
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic

Eligibility Criteria

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

Inclusion criteria:

  1. HCV genotype 1
  2. HCV viral load >100,000 IU/mL
  3. histology or fibroscan to rule out cirrhosis
  4. Absence of retinopathy
  5. treatment naive patients and treatment experienced patients
  6. Age 18 - 70 years
  7. Male OR female with documented hysterectomy OR postmenopausal

Exclusion criteria:

  1. Fertile males not willing to use an adequate form of contraception
  2. Pretreatment with any HCV-polymerase inhibitor
  3. Any concurrent disease if clinically significant based on the investigator's medical assessment
  4. Current alcohol or drug abuse, or history of the same
  5. Positive test for HIV or HBs
  6. History of malignancy
  7. Planned or concurrent usage of any other pharmacological therapy including any antiviral therapy or vaccination
  8. Usage of any investigational drug within thirty (30) days prior to enrolment or 5 halflives, whichever is longer
  9. Any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening
  10. Patients treated with any interferon (approved or investigational) or Peg-IFN and/or Ribavirin within 3 months prior to screening
  11. Known hypersensitivity to drugs or excipients; Further exclusion criteria apply

Sites / Locations

  • 1241.7.3307A CHU de Grenoble
  • 1241.7.3303A Hôpital Claude Huriez
  • 1241.7.3302A Hopital de l'Hotel Dieu
  • 1241.7.3301A Hôpital Saint Eloi
  • 1241.7.3305A HOP Archet 2
  • 1241.7.3306A Hôpital Haut-Lévêque
  • 1241.7.3304A HOP de Brabois
  • 1241.7.49010 Boehringer Ingelheim Investigational Site
  • 1241.7.49012 Boehringer Ingelheim Investigational Site
  • 1241.7.49004 Boehringer Ingelheim Investigational Site
  • 1241.7.49011 Boehringer Ingelheim Investigational Site
  • 1241.7.49001 Boehringer Ingelheim Investigational Site
  • 1241.7.49013 Boehringer Ingelheim Investigational Site
  • 1241.7.49009 Boehringer Ingelheim Investigational Site
  • 1241.7.49002 Boehringer Ingelheim Investigational Site
  • 1241.7.41003 Boehringer Ingelheim Investigational Site
  • 1241.7.41004 Boehringer Ingelheim Investigational Site
  • 1241.7.41001 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 207127 low dose + SOC

BI 207127 middle dose +SOC

BI 207127 high dose+SOC

Placebo + SOC

Arm Description

BI 207127 low dose tid + SOC

BI 207127 middle dose tid + SOC

BI 207127 high dose tid +SOC

Placebo tid +SOC

Outcomes

Primary Outcome Measures

Number of Participants With Virologic Response Defined as >= 3 Log Drop in Viral Load From Baseline at Day 28 With no Evidence of Virologic Rebound During These 28 Days. Virologic Rebound is Defined as >= 1 Log Increase in Viral Load From Nadir.
The primary efficacy endpoint is the number of participants with virologic response defined as >= 3 log drop in viral load from baseline at day 28 with no evidence of virologic rebound during these 28 days. Virologic rebound is defined as >= 1 log increase in viral load from nadir.

Secondary Outcome Measures

Viral Load (Log10) at Each Visit up to Day 28, Change From Baseline
Reductions of viral load (Log10) at each visit up to day 28, change from baseline. Change from baseline was calculated as the value at baseline minus the value at each later visit. A negative value represents an increase in viral load, a positive value represents a decrease in viral load.
Viral Load at Each Visit up to Day 28
Viral load (VL) (original values) at each visit up to day 28.
Number of Participants With Virologic Response at Day 28
Number of participants with virologic response at day 28, defined as achieving viral load below the limit of quantification (BLQ), <10 IU/mL, at day 28
Number of Participants With Rapid Virological Response
Number of participants with rapid virological response - defined as serum Hepatitis C virus (HCV) RNA level below the limit of detection (BLD) of the Roche COBAS Taqman HCV/High Pure System (HPS) for extraction assay (10 IU/mL) on Day 28.
Number of Participants With Early Virological Response
Number of participants with early virological response (EVR) defined as at least 2log10 reduction in HCV Ribonucleic acid (RNA) from baseline at Week 12. Number of responders* - Response = At least a 2 log10 reduction in viral load from baseline at Week 12 (Day 84)
Number of Participants With End of Treatment Response
Number of participants with end of treatment response (ETR) - defined as serum HCV RNA level below the limit of detection (BLD) of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at end of treatment (including 5-day washout). Number of responders* - Response = Viral load below the limit of detection at end of all treatment.
Number of Participants With Sustained Virological Response
Number of participants with sustained virological response. Sustained virological response was defined as serum HCV RNA below the limit of detection (<10 IU/mL) at least 85 days after stopping standard care (SOC).
Plasma Concentration Time Profiles of BI 207127
Plasma concentration time profiles of BI 207127
Plasma Concentration Time Profiles of CD 6168
Plasma concentration time profiles of CD 6168
Cmax of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State)
Maximum measured concentration of the analyte in plasma (Cmax) after first dose on day 1 (Cmax) and after last dose (steady state) on day 28 (Cmax,ss) of BI 207127 and CD 6168
Tmax of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State)
tmax [h] Time from (last) dosing to the maximum measured concentration of the analyte in plasma after first dose on day 1 and after last dose on day 28 (steady state).
AUC0-6 of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State)
Area under the concentration-time curve of the analyte in plasma (AUC) after first dose on day 1 (AUC0-6) and after last dose on day 28 (AUC0-6,ss) of BI 207127 and CD 6168
Cpre Pharmacokinetic Parameter of BI 207127 and CD 6168
Cpre,N [ng/mL] - Predose concentration of the analyte in plasma immediately before administration of the Nth dose after N-1 doses were administered for BI 207127 and CD 6168. Descriptive statistics were calculated only if at least 2/3 plasma concentrations were available. All values for Cpre,1 were not available, therefore no results are presented below.
C6,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
C6,ss Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose. C6,ss is the concentration 6 hours after dosing at steady-state (reported as 654 h).
AUC0-infinity,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
Area under the concentration time curve of the analyte in plasma over the time interval of 0 to infinity at steady state (AUC0-infinity,ss): Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State (SS) After the Last Dose
λz Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
Terminal rate constant in plasma (λz): Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose
t1/2,ss and MRTpo,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
Terminal half-life of the analyte in plasma at steady state (t1/2,ss) and mean residence time of the analyte in the body at steady state after oral administration (MRTpo,ss): Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose
RA,Cmax Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
Accumulation ratio of maximum measured concentration of the analyte in plasma (RA,Cmax): Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose. Ratio was calculated as Cmax,ss divided by Cmax.
Number of Participants With Clinical Relevant Abnormalities for Vital Signs, Body Temperature, Physical Examination, Blood Chemistry, Haematology, Coagulation, Urinalysis and ECG
Number of participants with clinically relevant abnormalities for vital signs, blood chemistry, body temperature, physical examination, haematology, coagulation, urinalysis and electrocardiography (ECG). New abnormal findings or worsening of baseline conditions were reported as adverse events.
Number of Participants With Discontinuations Due to AEs
Number of participants with adverse events (AEs) leading to discontinuation of trial drug

Full Information

First Posted
May 19, 2009
Last Updated
March 17, 2016
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT00905632
Brief Title
4 Week Combination of BI 207127 NA With Peg-IFN and Ribavirin in Chronic HCV Patients
Official Title
Safety, Antiviral Activity, and Pharmacokinetics of BI 207127 NA Administered in Combination With Peg-IFN and Ribavirin in Chronic HCV-infected Patients for 4 Weeks, a Randomised, Double-blind, Placebo Controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary
The main purpose of this clinical trial with BI 207127 is to see the effect of 4 week combination of BI 207127 with Peginterferon alfa (Peg-IFN) and Ribavirin (RBV) on hepatitis C virus (HCV) virus load and how safe BI 207127 is in this combination 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, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BI 207127 low dose + SOC
Arm Type
Experimental
Arm Description
BI 207127 low dose tid + SOC
Arm Title
BI 207127 middle dose +SOC
Arm Type
Experimental
Arm Description
BI 207127 middle dose tid + SOC
Arm Title
BI 207127 high dose+SOC
Arm Type
Experimental
Arm Description
BI 207127 high dose tid +SOC
Arm Title
Placebo + SOC
Arm Type
Placebo Comparator
Arm Description
Placebo tid +SOC
Intervention Type
Drug
Intervention Name(s)
BI 207127 middle dose +SOC
Intervention Description
BI 207127 middle dose tid + SOC
Intervention Type
Drug
Intervention Name(s)
BI 207127 high dose+SOC
Intervention Description
BI 207127 high dose tid +SOC
Intervention Type
Drug
Intervention Name(s)
Placebo + SOC
Intervention Description
Placebo tid +SOC
Intervention Type
Drug
Intervention Name(s)
BI 207127 low dose + SOC
Intervention Description
BI 207127 low dose tid + SOC
Primary Outcome Measure Information:
Title
Number of Participants With Virologic Response Defined as >= 3 Log Drop in Viral Load From Baseline at Day 28 With no Evidence of Virologic Rebound During These 28 Days. Virologic Rebound is Defined as >= 1 Log Increase in Viral Load From Nadir.
Description
The primary efficacy endpoint is the number of participants with virologic response defined as >= 3 log drop in viral load from baseline at day 28 with no evidence of virologic rebound during these 28 days. Virologic rebound is defined as >= 1 log increase in viral load from nadir.
Time Frame
Baseline and 4 weeks
Secondary Outcome Measure Information:
Title
Viral Load (Log10) at Each Visit up to Day 28, Change From Baseline
Description
Reductions of viral load (Log10) at each visit up to day 28, change from baseline. Change from baseline was calculated as the value at baseline minus the value at each later visit. A negative value represents an increase in viral load, a positive value represents a decrease in viral load.
Time Frame
Baseline and days 1, 2, 4, 8, 15, 22 and 28
Title
Viral Load at Each Visit up to Day 28
Description
Viral load (VL) (original values) at each visit up to day 28.
Time Frame
Baseline and days 8, 15, 22 and 28
Title
Number of Participants With Virologic Response at Day 28
Description
Number of participants with virologic response at day 28, defined as achieving viral load below the limit of quantification (BLQ), <10 IU/mL, at day 28
Time Frame
day 28
Title
Number of Participants With Rapid Virological Response
Description
Number of participants with rapid virological response - defined as serum Hepatitis C virus (HCV) RNA level below the limit of detection (BLD) of the Roche COBAS Taqman HCV/High Pure System (HPS) for extraction assay (10 IU/mL) on Day 28.
Time Frame
4 weeks
Title
Number of Participants With Early Virological Response
Description
Number of participants with early virological response (EVR) defined as at least 2log10 reduction in HCV Ribonucleic acid (RNA) from baseline at Week 12. Number of responders* - Response = At least a 2 log10 reduction in viral load from baseline at Week 12 (Day 84)
Time Frame
Baseline and week 12
Title
Number of Participants With End of Treatment Response
Description
Number of participants with end of treatment response (ETR) - defined as serum HCV RNA level below the limit of detection (BLD) of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at end of treatment (including 5-day washout). Number of responders* - Response = Viral load below the limit of detection at end of all treatment.
Time Frame
Week 12
Title
Number of Participants With Sustained Virological Response
Description
Number of participants with sustained virological response. Sustained virological response was defined as serum HCV RNA below the limit of detection (<10 IU/mL) at least 85 days after stopping standard care (SOC).
Time Frame
Until end of treatment, up to 570 days
Title
Plasma Concentration Time Profiles of BI 207127
Description
Plasma concentration time profiles of BI 207127
Time Frame
0.5 hours (h), 3h, 8h, 15h, 23.917h, 503.917h, 649h, 652h, 656h and 672h after drug administration
Title
Plasma Concentration Time Profiles of CD 6168
Description
Plasma concentration time profiles of CD 6168
Time Frame
0.5 hours (h), 3h, 8h, 15h, 23.917h, 503.917h, 649h, 652h, 656h and 672h after drug administration
Title
Cmax of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State)
Description
Maximum measured concentration of the analyte in plasma (Cmax) after first dose on day 1 (Cmax) and after last dose (steady state) on day 28 (Cmax,ss) of BI 207127 and CD 6168
Time Frame
5 min before drug admin and 30min, 1 hour (h), 2h, 3h, 4h, 5h 55min, 8h, 10h, 11h 55min and 15h after drug administration on day 1: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
Title
Tmax of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State)
Description
tmax [h] Time from (last) dosing to the maximum measured concentration of the analyte in plasma after first dose on day 1 and after last dose on day 28 (steady state).
Time Frame
5 min before drug admin and 30min, 1 hour (h), 2h, 3h, 4h, 5h 55min, 8h, 10h, 11h 55min and 15h after drug administration on day 1: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
Title
AUC0-6 of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State)
Description
Area under the concentration-time curve of the analyte in plasma (AUC) after first dose on day 1 (AUC0-6) and after last dose on day 28 (AUC0-6,ss) of BI 207127 and CD 6168
Time Frame
30min, 1 hour (h), 2h, 3h, 4h and 5h 55min after drug administration on day 1: 30min, 1h, 2h, 3h, 4h and 6h after admin on day 28
Title
Cpre Pharmacokinetic Parameter of BI 207127 and CD 6168
Description
Cpre,N [ng/mL] - Predose concentration of the analyte in plasma immediately before administration of the Nth dose after N-1 doses were administered for BI 207127 and CD 6168. Descriptive statistics were calculated only if at least 2/3 plasma concentrations were available. All values for Cpre,1 were not available, therefore no results are presented below.
Time Frame
5 minutes before drug administration on days 1, 2, 4, 8, 15, 22 and 27
Title
C6,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
Description
C6,ss Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose. C6,ss is the concentration 6 hours after dosing at steady-state (reported as 654 h).
Time Frame
654 hours after drug administration on day 28
Title
AUC0-infinity,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
Description
Area under the concentration time curve of the analyte in plasma over the time interval of 0 to infinity at steady state (AUC0-infinity,ss): Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State (SS) After the Last Dose
Time Frame
5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
Title
λz Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
Description
Terminal rate constant in plasma (λz): Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose
Time Frame
5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
Title
t1/2,ss and MRTpo,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
Description
Terminal half-life of the analyte in plasma at steady state (t1/2,ss) and mean residence time of the analyte in the body at steady state after oral administration (MRTpo,ss): Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose
Time Frame
5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
Title
RA,Cmax Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose
Description
Accumulation ratio of maximum measured concentration of the analyte in plasma (RA,Cmax): Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose. Ratio was calculated as Cmax,ss divided by Cmax.
Time Frame
5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28
Title
Number of Participants With Clinical Relevant Abnormalities for Vital Signs, Body Temperature, Physical Examination, Blood Chemistry, Haematology, Coagulation, Urinalysis and ECG
Description
Number of participants with clinically relevant abnormalities for vital signs, blood chemistry, body temperature, physical examination, haematology, coagulation, urinalysis and electrocardiography (ECG). New abnormal findings or worsening of baseline conditions were reported as adverse events.
Time Frame
From the start of the study to Day 30 (2 days after last dose)
Title
Number of Participants With Discontinuations Due to AEs
Description
Number of participants with adverse events (AEs) leading to discontinuation of trial drug
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: HCV genotype 1 HCV viral load >100,000 IU/mL histology or fibroscan to rule out cirrhosis Absence of retinopathy treatment naive patients and treatment experienced patients Age 18 - 70 years Male OR female with documented hysterectomy OR postmenopausal Exclusion criteria: Fertile males not willing to use an adequate form of contraception Pretreatment with any HCV-polymerase inhibitor Any concurrent disease if clinically significant based on the investigator's medical assessment Current alcohol or drug abuse, or history of the same Positive test for HIV or HBs History of malignancy Planned or concurrent usage of any other pharmacological therapy including any antiviral therapy or vaccination Usage of any investigational drug within thirty (30) days prior to enrolment or 5 halflives, whichever is longer Any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening Patients treated with any interferon (approved or investigational) or Peg-IFN and/or Ribavirin within 3 months prior to screening Known hypersensitivity to drugs or excipients; Further exclusion criteria apply
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
1241.7.3307A CHU de Grenoble
City
Grenoble cédex 9
Country
France
Facility Name
1241.7.3303A Hôpital Claude Huriez
City
Lille
Country
France
Facility Name
1241.7.3302A Hopital de l'Hotel Dieu
City
Lyon cedex 02
Country
France
Facility Name
1241.7.3301A Hôpital Saint Eloi
City
Montpellier
Country
France
Facility Name
1241.7.3305A HOP Archet 2
City
Nice Cedex 3
Country
France
Facility Name
1241.7.3306A Hôpital Haut-Lévêque
City
Pessac Cedex
Country
France
Facility Name
1241.7.3304A HOP de Brabois
City
Vandoeuvre
Country
France
Facility Name
1241.7.49010 Boehringer Ingelheim Investigational Site
City
Aachen
Country
Germany
Facility Name
1241.7.49012 Boehringer Ingelheim Investigational Site
City
Berlin
Country
Germany
Facility Name
1241.7.49004 Boehringer Ingelheim Investigational Site
City
Essen
Country
Germany
Facility Name
1241.7.49011 Boehringer Ingelheim Investigational Site
City
Freiburg
Country
Germany
Facility Name
1241.7.49001 Boehringer Ingelheim Investigational Site
City
Hamburg
Country
Germany
Facility Name
1241.7.49013 Boehringer Ingelheim Investigational Site
City
Mainz
Country
Germany
Facility Name
1241.7.49009 Boehringer Ingelheim Investigational Site
City
Regensburg
Country
Germany
Facility Name
1241.7.49002 Boehringer Ingelheim Investigational Site
City
Ulm
Country
Germany
Facility Name
1241.7.41003 Boehringer Ingelheim Investigational Site
City
Basel
Country
Switzerland
Facility Name
1241.7.41004 Boehringer Ingelheim Investigational Site
City
Lugano
Country
Switzerland
Facility Name
1241.7.41001 Boehringer Ingelheim Investigational Site
City
St. Gallen
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
22414766
Citation
Larrey D, Lohse AW, de Ledinghen V, Trepo C, Gerlach T, Zarski JP, Tran A, Mathurin P, Thimme R, Arasteh K, Trautwein C, Cerny A, Dikopoulos N, Schuchmann M, Heim MH, Gerken G, Stern JO, Wu K, Abdallah N, Girlich B, Scherer J, Berger F, Marquis M, Kukolj G, Bocher W, Steffgen J. Rapid and strong antiviral activity of the non-nucleosidic NS5B polymerase inhibitor BI 207127 in combination with peginterferon alfa 2a and ribavirin. J Hepatol. 2012 Jul;57(1):39-46. doi: 10.1016/j.jhep.2012.02.015. Epub 2012 Mar 10.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/
Description
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4 Week Combination of BI 207127 NA With Peg-IFN and Ribavirin in Chronic HCV Patients

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