Phase 1
Completed N=96
Safety, Antiviral Activity and PK of MRD of BI 201335 in Chronic Hepatitis C Patients Both Treatment Naive and -Experienced
Hepatitis C, Chronic
Source: ClinicalTrials.gov NCT00793793 ↗
Enrolled (actual)
96
Serious AEs
4.2%
Results posted
Sep 2015
Primary outcomePrimary: 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) — 0.00; 83.33; 100.00; 100.00 percentage of responders
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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) |
0.00; 83.33; 100.00; 100.00; 100.00; 100.00 | — |
| PRIMARY Occurrence of Adverse Events (AEs) During BI201335 + Washout Period |
62.5; 100.0; 100.0; 57.1; 100.0; 100.0 | — |
| PRIMARY Occurrence of Serious Adverse Events (SAEs) During BI201335 + Washout Period |
0.0; 16.7; 14.3; 0.0; 0.0; 0.0 | — |
| PRIMARY Occurrence of Laboratory Test Abnormalities and With Respect to Division of AIDS (DAIDS) Classification and Laboratory Test Values Change Over Time |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Maximum Viral Load Reduction From Baseline up to Day 14 for Treatment-naïve Patients and Day 28 Treatment for Treatment-experienced Patients |
-0.060; -3.049; -3.624; -3.740; -4.413; -5.023 | — |
| SECONDARY Change From Baseline in Viral Load on Day 14 for Treatment-naïve Patients and on Day 28 Treatment for Treatment-experienced Patients |
0.209; -1.226; -1.539; -0.781; -2.449; -5.023 | — |
| SECONDARY Rapid Virologic Response (RVR) |
0.00; 0.00; 28.57; 14.29; 16.67; 33.33 | — |
| SECONDARY Early Virologic Response (EVR) |
0.0; 100.0; 100.0; 85.7; 83.3; 83.3 | — |
| SECONDARY Complete EVR1 (cEVR1) |
0.0; 16.7; 28.6; 28.6; 50.0; 50.0 | — |
| SECONDARY Complete EVR2 (cEVR2) |
0.0; 0.0; 28.6; 14.3; 33.3; 50.0 | — |
| SECONDARY End of Treatment Response (ETR) |
0.0; 83.3; 57.1; 57.1; 66.7; 33.3 | — |
| SECONDARY Sustained Virologic Response (SVR) |
0.0; 50.0; 42.9; 42.9; 50.0; 50.0 | — |
| SECONDARY Achievement of an HCV RNA Level Below the Limit of Detection Over Time |
0.0; 0.0; 28.6; 14.3; 16.7; 33.3 | — |
| SECONDARY Achievement of an HCV RNA Level Below the Limit of Quantification Over Time |
0.0; 16.7; 28.6; 28.6; 50.0; 50.0 | — |
| SECONDARY Achievement of a >= 2 log10 Reduction in Plasma HCV RNA Level From Baseline Over Time |
0.0; 83.3; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY Occurrence of AEs, by Action Taken With Regard to Study Medication |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Occurrence of Discontinuations Due to AEs During BI201335 or BI201335+PegIFN/RBV Combination Treatment Period |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY PK (Pharmacokinetic) Parameter After the First Dose: Cmax ( Maximum Measured Concentration of the Analyte in Plasma) |
45.3; 170; 964; 2910; 164; 954 | — |
| SECONDARY PK Parameter After the First Dose: Tmax (Time From (Last) Dosing to the Maximum Measured Concentration of the Analyte in Plasma) |
7.07; 2.48; 2.12; 3.89; 3.89; 2.25 | — |
| SECONDARY 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) |
736; 2650; 11600; 35700; 2550; 12300 | — |
| SECONDARY 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) |
150; 616; 4050; 15400; 478; 4170 | — |
| SECONDARY 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 ) |
4.89; 3.38; 2.75; 3.36; 2.15; 1.94 | — |
| SECONDARY PK Parameter at Steady State After the Last Dose: Cmin,ss (Minimum Measured Concentration of the Analyte in Plasma) |
68.0; 199; 1120; 4040; 147; 863 | — |
| SECONDARY 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) |
2460; 8520; 49400; 185000; 6820; 43400 | — |
| SECONDARY PK Parameter at Steady State After the Last Dose: t1/2,ss (Terminal Half-life of the Analyte in Plasma at Steady State ) |
30.5; 38.8; 25.5; 19.3; 33.2; 22.5 | — |
| SECONDARY 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) |
44.4; 60.2; 33.3; 26.7; 39.7; 26.6 | — |
| SECONDARY 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 ) |
136; 93.9; 40.4; 21.6; 117; 46.1 | — |
| SECONDARY 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 ) |
358; 315; 89.4; 36.1; 337; 89.9 | — |
| SECONDARY 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 ) |
1970; 8740; 45800; 180000 | — |
| SECONDARY PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): Cmax,ss |
106; 693; 3880; 13100 | — |
| SECONDARY PK Parameter for Drug-drug Interaction (naïve Patients With ≥1 Log Reduction on Day 10): Cmin, ss |
57.8; 185; 1010; 4320 | — |
| SECONDARY Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAcmax |
2.34; 4.08; 3.74; 4.49; 2.91; 4.37 | — |
| SECONDARY Accumulation Ratio of the Analyte in Plasma Following Multiple Doses Over a Uniform Dosing Interval: RAauc |
2.68; 3.30; 3.61; 5.03; 2.68; 3.52 | — |
Eligibility 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
- Patients who have been previously treated with at least one dose of any protease inhibitor for acute or chronic hepatitis C infection
- Evidence of liver disease due to causes other than chronic HCV infection
- Positive ELISA for HIV-1 or HIV-2
- Hepatitis B virus (HBV) infection based on presence of Hbs Ag or HBV DNA
- Any previous liver biopsy consistent with cirrhosis
- Decompensated liver diseases as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy
- Haemophilia
- Hemoglobinopathy (e.g., thalassemia major or sickle cell anemia)
- Severe pre-existing psychiatric disease
- Poorly controlled diabetes mellitus
- Ischaemic heart disease
- Chronic obstructive airway disease
- Autoimmune disease; including autoimmune hepatitis
- History of alcohol abuse within the past 12 months
- Hyperbilirubinemia (conjugated bilirubin) >1.5x ULN
- Alkaline phosphatase >1.5x ULN
- ALT and AST levels >= 5 x ULN
- Hemoglobin 1.5 x ULN
- 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
- Known hypersensitivity to study drugs
Data sourced from ClinicalTrials.gov (NCT00793793). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.