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

Phase 2

Completed

• Conditions: Hepatitis C, Chronic
• Interventions: Drug: peginterferon; Drug: Ribavirin; Drug: BI 207127 NA; Drug: BI 201335 NA

• Registration Number: NCT01528735
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2012-02
• Study First Submitted: 2012-02-06
• Study First Submitted QC: 2012-02-06
• Study First Posted: 2012-02-08
• Primary Completion: 2013-08
• Study Completion: 2013-08
• Disposition First Submitted: 2014-04-30
• Disposition First Submitted QC: 2014-04-30
• Disposition First Posted: 2014-05-16
• Results First Submitted: 2016-01-21
• Status Verified: 2016-03
• Results First Submitted QC: 2016-03-14
• Last Update Submitted: 2016-03-14
• Results First Posted: 2016-04-13
• Last Update Posted: 2016-04-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BI 207127 NA, BI 201335 NA(high dose), R	peginterferon	Patients receive BI 207127 NA,BI 201335 NA(high dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
BI 207127 NA, BI 201335 NA(high dose), R	Ribavirin	Patients receive BI 207127 NA,BI 201335 NA(high dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
BI 207127 NA, BI 201335 NA(high dose), R	BI 207127 NA	Patients receive BI 207127 NA,BI 201335 NA(high dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
BI 207127 NA, BI 201335 NA(high dose), R	BI 201335 NA	Patients receive BI 207127 NA,BI 201335 NA(high dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
BI 207127 NA,BI 201335 NA(low dose),RBV	BI 207127 NA	Patients receive BI 207127 NA,BI 201335 NA(low dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
BI 207127 NA,BI 201335 NA(low dose),RBV	BI 201335 NA	Patients receive BI 207127 NA,BI 201335 NA(low dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
BI 207127 NA,BI 201335 NA(low dose),RBV	peginterferon	Patients receive BI 207127 NA,BI 201335 NA(low dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks
BI 207127 NA,BI 201335 NA(low dose),RBV	Ribavirin	Patients receive BI 207127 NA,BI 201335 NA(low dose) and RBV for 8 wks followed by BI 201335 NA,PegIFN/RBV for 24 wks

Primary Outcome Measures

Name	Time	Method
Number of Patients With Drug-related Adverse Events	From first dose of study medication until 30 days after last dose of study medication, up to 199 days	Number of patients with investigator defined drug-related Adverse Events

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Virological Response at Week 8	8 weeks	Percentage of participants with plasma HCV RNA (hepatitis C virus ribonucleic acid ) level \<25 IU/mL (undetected or detected) at week 8.
Percentage of Participants With Virological Response at Week 4	4 weeks	Percentage of participants with plasma HCV RNA (hepatitis C virus (HCV) ribonucleic acid (RNA)) level \<25 IU/mL (undetected or detected) at week 4.
Maximum Measured Concentration (Cmax) of Deleobuvir	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 of BI 207127 (Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Maximum Measured Concentration (Cmax) of Faldaprevir	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 of Faldaprevir (BI 201335 ZW) in plasma following the morning dose of Nth day (Cmax,N).
Maximum Measured Concentration (Cmax) of CD 6168	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	Maximum measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir	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 of Deleobuvir (BI 207127) in plasma after the morning dose of Nth day (Tmax,N).
Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir	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 of Faldaprevir (BI 201335 ZW) in plasma after the morning dose of Nth day (Tmax,N).
Maximum Measured Concentration (Cmax) of BI 208333	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 of BI 208333 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG	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 of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N). AG=acylglucuronide.
Area Under the Curve (AUC) of Deleobuvir	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 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 From Last Dosing to the Maximum Concentration (Tmax) of BI 208333	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 of BI 208333 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).
Area Under the Curve (AUC) of Faldaprevir	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 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.
Area Under the Curve (AUC) of CD 6168	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 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.
Predose Measured Concentration of Deleobuvir	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	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).
Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir	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	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).
Area Under the Curve (AUC) of BI 208333	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 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.
Maximum Measured Concentration (Cmax) of CD 6168-AG	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	Maximum measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). AG=acylglucuronide.
Area Under the Curve (AUC) of CD 6168-AG	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 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 From Last Dosing to the Maximum Concentration (Tmax) of CD 6168	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 of CD 6168 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).
AUC Accumulation Ratio of Faldaprevir	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	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).
Mean Residence Time (MRTpo,ss) of Faldaprevir	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	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.
Maximum Measured Concentration (Cmax) of RBV	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	Maximum measured concentration of ribavirin (RBV) in plasma following the morning dose of Nth day (Cmax,N).
Time From Last Dosing to the Maximum Concentration (Tmax) of RBV	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 of ribavirin (RBV) in plasma after the morning dose of Nth day (Tmax,N).
Area Under the Curve (AUC) of RBV	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 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.
Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir	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	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).
AUC Accumulation Ratio of Deleobuvir	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	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).
Mean Residence Time (MRTpo,ss) of Deleobuvir	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	Mean residence time of BI 207127 (Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).
Apparent Clearance (CL/F,ss) of Deleobuvir	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 of BI 207127 (Deleobuvir) in plasma following extravascular administration on the 57th day (CL/F,ss).
Apparent Clearance (CL/F,ss) of Faldaprevir	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 of Faldaprevir (BI 201335 ZW) in plasma following extravascular administration on the 57th day (CL/F,ss).
Predose Measured Concentration of Faldaprevir	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	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).
Cmax Accumulation Ratio of BI 208333	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	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).
AUC Accumulation Ratio of BI 208333	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	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).
Mean Residence Time (MRTpo,ss) of BI 208333	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	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.
Predose Measured Concentration of BI 208333	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	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).
Cmax Accumulation Ratio of CD 6168	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	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).
AUC Accumulation Ratio of CD 6168	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	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).
Mean Residence Time (MRTpo,ss) of CD 6168	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	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.
Predose Measured Concentration of CD 6168	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	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).
Cmax Accumulation Ratio of CD 6168-AG	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	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.
AUC Accumulation Ratio of CD 6168-AG	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	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.
Mean Residence Time (MRTpo,ss) of CD 6168-AG	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	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.
Predose Measured Concentration of CD 6168-AG	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	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.
AUC Accumulation Ratio of RBV	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	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).
Cmax Accumulation Ratio (RA,Cmax,57) of RBV	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	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).
Mean Residence Time (MRTpo,ss) of RBV	10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on day 57	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.
Predose Measured Concentration of RBV	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	Predose measured concentration of ribavirin (RBV) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Trial Locations

Locations (5)

1241.25.002 Boehringer Ingelheim Investigational Site; 🇯🇵 Kofu, Yamanashi, Japan

1241.25.001 Boehringer Ingelheim Investigational Site; 🇯🇵 Omura, Nagasaki, Japan

1241.25.005 Boehringer Ingelheim Investigational Site; 🇯🇵 Kurashiki, Okayama, Japan

1241.25.004 Boehringer Ingelheim Investigational Site; 🇯🇵 Nishinomiya, Hyogo, Japan

1241.25.003 Boehringer Ingelheim Investigational Site; 🇯🇵 Nagoya, Aichi, Japan