This Trial Evaluates Safety, Pharmacokinetic Profile and Anti-viral Response of BI 207127 and BI 201335 for Patients With Chronic Hepatitis C

Boehringer Ingelheim25 enrolled

Overview

The objective of this trial is to investigate tolerability, safety, pharmacokinetics and antiviral activity of BI 207127 NA in combination with BI 201335 NA and ribavirin for 8 weeks in Japanese treatment-naive patients with chronic GT-1 HCV infection.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatitis C, Chronic

Interventions

BI 207127 NADRUG

one fix dose

peginterferonDRUG

per package insert

RibavirinDRUG

per weight BID

Ribavirin

Eligibility

Sex: ALLMin age: 20 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion criteria: * Chronic hepatitis C, diagnosed by positive anti-hepatitis C virus(HCV) antibodies and detected HCV ribonucleic acid(RNA) at screening in addition to: 1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening; or, 2. liver biopsy consistent with chronic HCV infection. * HCV infection of genotype 1 confirmed by genotypic testing at screening * Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection. * Plasma HCV RNA = 100,000 IU/mL at screening Exclusion criteria: * Hepatitis C infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening * Human immunodeficiency virus (HIV) co-infection * Decompensated liver disease, or history of decompensated liver disease * Body weight \< 40 or \> 125 kg at screening * Hemoglobin \<12.0g/dL for women and \<13.0g/dL for men at screening * White blood cell count \<3000 cells/mm3 at screening * Absolute neutrophil count \< 1,500 cells/mm3 at screening * Platelet count \< 90,000 /mm3 at screening * Serum creatinine \> 1.5xUpper Limit of Normal range(ULN) or creatinine clearance =50 mL/min at screening

Locations (5)

1241.25.002 Boehringer Ingelheim Investigational Site

Kofu, Yamanashi, Japan

1241.25.005 Boehringer Ingelheim Investigational Site

Kurashiki, Okayama, Japan

1241.25.003 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, Japan

1241.25.004 Boehringer Ingelheim Investigational Site

Nishinomiya, Hyogo, Japan

Outcomes

Primary Outcomes

Number of Patients With Drug-related Adverse Events

Number of patients with investigator defined drug-related Adverse Events

Time frame: From first dose of study medication until 30 days after last dose of study medication, up to 199 days

Secondary Outcomes

Percentage of Participants With Virological Response at Week 4

Percentage of participants with plasma HCV RNA (hepatitis C virus (HCV) ribonucleic acid (RNA)) level \<25 IU/mL (undetected or detected) at week 4.

Time frame: 4 weeks

Percentage of Participants With Virological Response at Week 8

Percentage of participants with plasma HCV RNA (hepatitis C virus ribonucleic acid ) level \<25 IU/mL (undetected or detected) at week 8.

Time frame: 8 weeks

Maximum Measured Concentration (Cmax) of Deleobuvir

Maximum measured concentration of BI 207127 (Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir

Time from last dosing to the maximum concentration of Deleobuvir (BI 207127) in plasma after the morning dose of Nth day (Tmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area Under the Curve (AUC) of Deleobuvir

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Data from ClinicalTrials.gov

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BI 207127 NADRUG

one fix dose

BI 201335 NADRUG

high dose

BI 201335 NADRUG

low dose

peginterferonDRUG

per package insert

1241.25.001 Boehringer Ingelheim Investigational Site

Omura, Nagasaki, Japan

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Maximum Measured Concentration (Cmax) of Faldaprevir

Maximum measured concentration of Faldaprevir (BI 201335 ZW) in plasma following the morning dose of Nth day (Cmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir

Time from last dosing to the maximum concentration of Faldaprevir (BI 201335 ZW) in plasma after the morning dose of Nth day (Tmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area Under the Curve (AUC) of Faldaprevir

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Maximum Measured Concentration (Cmax) of BI 208333

Maximum measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333

Time from last dosing to the maximum concentration of BI 208333 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area Under the Curve (AUC) of BI 208333

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Maximum Measured Concentration (Cmax) of CD 6168

Maximum measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168

Time from last dosing to the maximum concentration of CD 6168 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area Under the Curve (AUC) of CD 6168

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Maximum Measured Concentration (Cmax) of CD 6168-AG

Maximum measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). AG=acylglucuronide.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG

Time from last dosing to the maximum concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N). AG=acylglucuronide.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area Under the Curve (AUC) of CD 6168-AG

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. AG=acylglucuronide.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Maximum Measured Concentration (Cmax) of RBV

Maximum measured concentration of ribavirin (RBV) in plasma following the morning dose of Nth day (Cmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Time From Last Dosing to the Maximum Concentration (Tmax) of RBV

Time from last dosing to the maximum concentration of ribavirin (RBV) in plasma after the morning dose of Nth day (Tmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Area Under the Curve (AUC) of RBV

Area under the concentration time curve (AUC) of ribavirin (RBV) in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir

Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of Deleobuvir versus itself (RA,Cmax,Met,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

AUC Accumulation Ratio of Deleobuvir

Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of Deleobuvir versus itself (RA,AUC,Met,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Mean Residence Time (MRTpo,ss) of Deleobuvir

Mean residence time of BI 207127 (Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Apparent Clearance (CL/F,ss) of Deleobuvir

Apparent clearance of BI 207127 (Deleobuvir) in plasma following extravascular administration on the 57th day (CL/F,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Predose Measured Concentration of Deleobuvir

Predose measured concentration of BI 207127 (Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57

Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir

Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

AUC Accumulation Ratio of Faldaprevir

Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Mean Residence Time (MRTpo,ss) of Faldaprevir

Mean residence time of Faldaprevir (BI 201335 ZW) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Apparent Clearance (CL/F,ss) of Faldaprevir

Apparent clearance of Faldaprevir (BI 201335 ZW) in plasma following extravascular administration on the 57th day (CL/F,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Predose Measured Concentration of Faldaprevir

Predose measured concentration of Faldaprevir (BI 201335 ZW) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57

Cmax Accumulation Ratio of BI 208333

Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of BI 208333 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

AUC Accumulation Ratio of BI 208333

Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of BI 208333 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Mean Residence Time (MRTpo,ss) of BI 208333

Mean residence time of BI 208333 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Predose Measured Concentration of BI 208333

Predose measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57

Cmax Accumulation Ratio of CD 6168

Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

AUC Accumulation Ratio of CD 6168

Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Mean Residence Time (MRTpo,ss) of CD 6168

Mean residence time of CD 6168 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57

Predose Measured Concentration of CD 6168

Predose measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57

Cmax Accumulation Ratio of CD 6168-AG

Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168-AG versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss). AG=acylglucuronide.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

AUC Accumulation Ratio of CD 6168-AG

Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168-AG versus AUC,ss of Deleobuvir (RA,AUC,Met,ss). AG=acylglucuronide.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Mean Residence Time (MRTpo,ss) of CD 6168-AG

Mean residence time of CD 6168-AG (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). AG=acylglucuronide. This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57

Predose Measured Concentration of CD 6168-AG

Predose measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). AG=acylglucuronide.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57

AUC Accumulation Ratio of RBV

Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the 57th day and after the first dose (RA,AUC,57).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Cmax Accumulation Ratio (RA,Cmax,57) of RBV

Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the 57th day and after the first dose (RA,Cmax,57).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Mean Residence Time (MRTpo,ss) of RBV

Mean residence time of ribavirin (RBV) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on day 57

Predose Measured Concentration of RBV

Predose measured concentration of ribavirin (RBV) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Time frame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 11 and 57