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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00905632
First received: May 19, 2009
Last updated: March 17, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Hepatitis C, Chronic
Drug: BI 207127 middle dose +SOC
Drug: BI 207127 high dose+SOC
Drug: Placebo + SOC
Drug: BI 207127 low dose + SOC
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

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. [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and days 1, 2, 4, 8, 15, 22 and 28 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and days 8, 15, 22 and 28 ] [ Designated as safety issue: No ]
    Viral load (VL) (original values) at each visit up to day 28.

  • Number of Participants With Virologic Response at Day 28 [ Time Frame: day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Until end of treatment, up to 570 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0.5 hours (h), 3h, 8h, 15h, 23.917h, 503.917h, 649h, 652h, 656h and 672h after drug administration ] [ Designated as safety issue: No ]
    Plasma concentration time profiles of BI 207127

  • 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 minutes before drug administration on days 1, 2, 4, 8, 15, 22 and 27 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 654 hours after drug administration on day 28 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the start of the study to Day 30 (2 days after last dose) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Number of participants with adverse events (AEs) leading to discontinuation of trial drug


Enrollment: 75
Study Start Date: May 2009
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 207127 low dose + SOC
BI 207127 low dose tid + SOC
Drug: BI 207127 low dose + SOC
BI 207127 low dose tid + SOC
Experimental: BI 207127 middle dose +SOC
BI 207127 middle dose tid + SOC
Drug: BI 207127 middle dose +SOC
BI 207127 middle dose tid + SOC
Experimental: BI 207127 high dose+SOC
BI 207127 high dose tid +SOC
Drug: BI 207127 high dose+SOC
BI 207127 high dose tid +SOC
Placebo Comparator: Placebo + SOC
Placebo tid +SOC
Drug: Placebo + SOC
Placebo tid +SOC

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00905632

Locations
France
1241.7.3307A CHU de Grenoble
Grenoble cédex 9, France
1241.7.3303A Hôpital Claude Huriez
Lille, France
1241.7.3302A Hopital de l'Hotel Dieu
Lyon cedex 02, France
1241.7.3301A Hôpital Saint Eloi
Montpellier, France
1241.7.3305A HOP Archet 2
Nice Cedex 3, France
1241.7.3306A Hôpital Haut-Lévêque
Pessac Cedex, France
1241.7.3304A HOP de Brabois
Vandoeuvre, France
Germany
1241.7.49010 Boehringer Ingelheim Investigational Site
Aachen, Germany
1241.7.49012 Boehringer Ingelheim Investigational Site
Berlin, Germany
1241.7.49004 Boehringer Ingelheim Investigational Site
Essen, Germany
1241.7.49011 Boehringer Ingelheim Investigational Site
Freiburg, Germany
1241.7.49001 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1241.7.49013 Boehringer Ingelheim Investigational Site
Mainz, Germany
1241.7.49009 Boehringer Ingelheim Investigational Site
Regensburg, Germany
1241.7.49002 Boehringer Ingelheim Investigational Site
Ulm, Germany
Switzerland
1241.7.41003 Boehringer Ingelheim Investigational Site
Basel, Switzerland
1241.7.41004 Boehringer Ingelheim Investigational Site
Lugano, Switzerland
1241.7.41001 Boehringer Ingelheim Investigational Site
St. Gallen, Switzerland
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00905632     History of Changes
Other Study ID Numbers: 1241.7  2008-008292-34 
Study First Received: May 19, 2009
Results First Received: January 21, 2016
Last Updated: March 17, 2016
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Swissmedic

Additional relevant MeSH terms:
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Chronic
Ribavirin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 21, 2016