Safety, Antiviral Activity and PK of MRD of BI 201335 in Chronic Hepatitis C Patients Both Treatment Naive and -Experienced

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00793793
First received: September 23, 2008
Last updated: August 18, 2015
Last verified: August 2015
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: BI201335
Drug: Placebo
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 Multiple Rising Oral Doses of BI 201335 NA in Treatment-naïve Patients With Chronic Hepatitis C Infection for 14 Days Monotherapy Followed by Combination With Pegylated Interferon and Ribavirin for an Additional 14 Days (Double-blind, Placebo Controlled), and in Treatment-experienced Patients With Chronic Hepatitis C Infection for 28 Days as Combination Therapy With Pegylated Interferon and Ribavirin (Open-label)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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) [ Time Frame: Baseline and up to 4 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: from day 1 and up to 4 weeks + 4 days washout ] [ Designated as safety issue: No ]
    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 [ Time Frame: from day 1 and up to 4 weeks + 4 days washout ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and up to 4 weeks ] [ Designated as safety issue: No ]

    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:
  • Maximum Viral Load Reduction From Baseline up to Day 14 for Treatment-naïve Patients and Day 28 Treatment for Treatment-experienced Patients [ Time Frame: Baseline and up to 4 weeks ] [ Designated as safety issue: No ]
    Maximum viral load reduction from baseline up to Day 14 for treatment-naïve patients and Day 28 treatment for treatment-experienced patients.

  • Change From Baseline in Viral Load on Day 14 for Treatment-naïve Patients and on Day 28 Treatment for Treatment-experienced Patients [ Time Frame: Baseline and up to 4 weeks ] [ Designated as safety issue: No ]
    Change from baseline in viral load on Day 14 for treatment-naïve patients and on Day 28 treatment for treatment-experienced patients.

  • Rapid Virologic Response (RVR) [ Time Frame: week 4 ] [ Designated as safety issue: No ]
    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.

  • Early Virologic Response (EVR) [ Time Frame: week 12 ] [ Designated as safety issue: No ]
    Early Virologic Response (EVR): >=2 log10 reduction in plasma HCV RNA level from baseline at week 12 (day 84)

  • Complete EVR1 (cEVR1) [ Time Frame: week 4 and week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: week 4 and week 12 ] [ Designated as safety issue: No ]
    VL below the limit of detection at both 4 weeks and 12 weeks

  • End of Treatment Response (ETR) [ Time Frame: week 48 ] [ Designated as safety issue: No ]
    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).

  • Sustained Virologic Response (SVR) [ Time Frame: week 72 ] [ Designated as safety issue: No ]
    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).

  • Achievement of an HCV RNA Level Below the Limit of Detection Over Time [ Time Frame: from day 1 and up to 4 weeks ] [ Designated as safety issue: No ]
    Achievement of an HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) over time

  • Achievement of an HCV RNA Level Below the Limit of Quantification Over Time [ Time Frame: from day 1 and up to 4 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: from day 1 and up to 4 weeks ] [ Designated as safety issue: No ]
    Achievement of a >= 2 log10 reduction in plasma HCV RNA level from baseline over time.

  • Occurrence of AEs, by Action Taken With Regard to Study Medication [ Time Frame: from day 1 and up to 4 weeks ] [ Designated as safety issue: No ]
    Occurrence of AEs, by action taken with regard to study medication.

  • Occurrence of Discontinuations Due to AEs During BI201335 or BI201335+PegIFN/RBV Combination Treatment Period [ Time Frame: from day 1 and up to 4 weeks ] [ Designated as safety issue: No ]
    Occurrence of discontinuations due to AEs during BI201335 or BI201335+PegIFN/RBV combination treatment period.

  • PK (Pharmacokinetic) Parameter After the First Dose: Cmax ( Maximum Measured Concentration of the Analyte in Plasma) [ Time Frame: 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) ] [ Designated as safety issue: No ]

    PK (pharmacokinetic) parameter after the first dose: Cmax ( Maximum measured concentration of the analyte in plasma ).


  • PK Parameter After the First Dose: Tmax (Time From (Last) Dosing to the Maximum Measured Concentration of the Analyte in Plasma) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    PK parameter after the first dose: tmax (Time from (last) dosing to the 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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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: Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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: Tmax,ss (Time From Last Dosing to the Maximum Measured Concentration of the Analyte in Plasma at Steady State ) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 ).

  • PK Parameter at Steady State After the Last Dose: Cmin,ss (Minimum Measured Concentration of the Analyte in Plasma) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    PK parameter at steady state after the last dose: Cmin,ss (Minimum measured concentration of the analyte in plasma).

  • 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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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: t1/2,ss (Terminal Half-life of the Analyte in Plasma at Steady State ) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    PK parameter at steady state after the last dose: t1/2,ss (Terminal half-life of the analyte in plasma at steady state [h] )

  • 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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 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 ) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 ) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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] )

  • 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 ) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 ).

  • PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): Cmax,ss [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    PK parameter for drug-drug interaction (naïve patients with ≥1 log reduction on Day 10): Cmin, ss.

  • Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAcmax [ Time Frame: Day 1, Day 14, and Day 28 ] [ Designated as safety issue: No ]
    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.

  • Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAauc [ Time Frame: Day 1, Day 14, and Day 28 ] [ Designated as safety issue: No ]
    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.


Enrollment: 96
Study Start Date: September 2007
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 20mg
patient to receive 20mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
Drug: BI201335
patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
Experimental: 48mg
patient to receive 48mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
Drug: BI201335
patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days
Experimental: 120mg
patient to receive 120mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
Drug: BI201335
patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days
Experimental: 240mg
patient to receive 240mg solution BI201335 qd +/- PegIFN/RBV fore 28 days
Drug: BI201335
patient to receive rising doses of BI201335 solution qd +/- PegIFN/RBV fore 28 days
Placebo Comparator: Placebo Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

1a. For treatment-naïve patients: no prior therapy with interferon, peginterferon, or ribavirin for acute or chronic hepatitis C infection

1b. For treatment-experienced patients: confirmed virological failure during or after combination treatment with an approved dose of alfa-2a or alfa-2b peginterferon combined with ribavirin; such patients must have received at least 12 weeks of therapy with a 90 day washout period prior to screening and must have documentation of medical history prior to enrolment in 1220.2 2. Age 18 years or older 3. Signed informed consent form prior to trial participation 4. Male or female with documented hysterectomy or menopausal female with last menstrual period at least 6 months prior to screening 5. Chronic hepatitis C infection of genotype 1, diagnosed by positive HCV serology test (HCV Ab positive) or detectable HCV RNA at least 6 months prior to screening 6. HCV viral load >= 100,000 IU/mL at screening 7. TSH and T4 within normal limits or adequately controlled thyroid function 8. Histological evidence within 36 months prior to study enrolment of any degree of chronic necroinflammatory activity or the presence of fibrosis (Ishak Grade 1-4 or Metavir Grade 1-3)

Exclusion criteria:

  1. Patients who have been previously treated with at least one dose of any protease inhibitor for acute or chronic hepatitis C infection
  2. Evidence of liver disease due to causes other than chronic HCV infection
  3. Positive ELISA for HIV-1 or HIV-2
  4. Hepatitis B virus (HBV) infection based on presence of Hbs Ag or HBV DNA
  5. Any previous liver biopsy consistent with cirrhosis
  6. Decompensated liver diseases as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy
  7. Haemophilia
  8. Hemoglobinopathy (e.g., thalassemia major or sickle cell anemia)
  9. Severe pre-existing psychiatric disease
  10. Poorly controlled diabetes mellitus
  11. Ischaemic heart disease
  12. Chronic obstructive airway disease
  13. Autoimmune disease; including autoimmune hepatitis
  14. History of alcohol abuse within the past 12 months
  15. Hyperbilirubinemia (conjugated bilirubin) >1.5x ULN
  16. Alkaline phosphatase >1.5x ULN
  17. ALT and AST levels >= 5 x ULN
  18. Hemoglobin < 12.0 g/dL for women and < 13.0 g/dL for men
  19. White blood cell count < 2000 cells/mm3
  20. Absolute Neutrophil Count < 1500 cells/mm3
  21. Platelet count < 100,000 cells/mm3
  22. Prothrombin time INR (Institutional Normalized Ratio) prolonged to > 1.5 x ULN
  23. Usage of any investigational drug within 30 days prior to enrolment; or the planned usage of an investigational drug during the course of the current study
  24. Known hypersensitivity to study drugs
  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: NCT00793793

Locations
United States, California
1220.2.10 Boehringer Ingelheim Investigational Site
San Francisco, California, United States
1220.2.15 Boehringer Ingelheim Investigational Site
San Francisco, California, United States
United States, Maryland
1220.2.17 Boehringer Ingelheim Investigational Site
Baltimore, Maryland, United States
United States, New York
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
United States, Texas
1220.2.14 Boehringer Ingelheim Investigational Site
Austin, Texas, United States
France
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
Germany
1220.2.49002 Boehringer Ingelheim Investigational Site
Berlin, Germany
1220.2.49005 Boehringer Ingelheim Investigational Site
Düsseldorf, Germany
1220.2.49006 Boehringer Ingelheim Investigational Site
Hannover, Germany
1220.2.49004 Boehringer Ingelheim Investigational Site
Kiel, Germany
1220.2.49003 Boehringer Ingelheim Investigational Site
Mainz, Germany
Spain
1220.2.34001 Boehringer Ingelheim Investigational Site
Madrid, Spain
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: NCT00793793     History of Changes
Other Study ID Numbers: 1220.2  2007-001158-19 
Study First Received: September 23, 2008
Results First Received: July 3, 2015
Last Updated: August 18, 2015
Health Authority: France: AFSSAPS
Germany: BfArM-Bundesinstitut fuer Arzneimittel und Medizinprodukte (Federal Authoriteis for Drugs and Medical Devices)
Spain: Spanish Agency for Medicines and Health Products
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis C, Chronic
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on May 05, 2016