Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 201335 as Softgel Capsule in Naive Hepatitis C Virus (HCV) Patients

Phase 2

Completed

• Conditions: Hepatitis C; Pharmacokinetics
• Interventions: Drug: pegylated interferon (PegIFN) alfa-2a; Drug: Placebo; Drug: BI 201335 NA low placebo; Drug: ribavirin (RBV); Drug: BI 201335 NA high; Drug: BI 201335 NA low; Drug: BI 201335 NA high placebo

• Registration Number: NCT00947349
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The current Standard of Care (SOC) for chronic HCV infection, which is pegylated interferon-alfa as combination therapy with ribavirin for 24-48 weeks of treatment, is effective in only part of the patients and is often associated with severe adverse effects leading to discontinuation of treatment and dose modifications.

A number of compounds with direct activity are currently under clinical development, incl. BI 201335. BI 201335 works by preventing the Hepatitis C virus from replicating by binding to the HCV protease (enzyme). The main purpose of this clinical trial with BI 201335 is to see how well BI 201335 works and how safe BI 201335 is to use daily in combination with PegIFN and RBV in HCV infected patients

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: 2009-07
• Study First Submitted: 2009-07-21
• Study First Submitted QC: 2009-07-27
• Study First Posted: 2009-07-28
• Primary Completion: 2011-08
• Study Completion: 2011-08
• Disposition First Submitted: 2014-07-10
• Disposition First Submitted QC: 2014-07-10
• Disposition First Posted: 2014-07-11
• Results First Submitted: 2015-01-22
• Status Verified: 2015-07
• Results First Submitted QC: 2015-07-03
• Last Update Submitted: 2015-07-03
• Results First Posted: 2015-07-07
• Last Update Posted: 2015-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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 201335 NA low TN	pegylated interferon (PegIFN) alfa-2a	patient to receive a capsule containing low dose of BI 201335 NA/Drug for treatment-naive (TN) patients
BI 201335 NA low TN	BI 201335 NA low	patient to receive a capsule containing low dose of BI 201335 NA/Drug for treatment-naive (TN) patients
BI 201335 NA low TN	ribavirin (RBV)	patient to receive a capsule containing low dose of BI 201335 NA/Drug for treatment-naive (TN) patients
BI 201335 NA low TN	BI 201335 NA low placebo	patient to receive a capsule containing low dose of BI 201335 NA/Drug for treatment-naive (TN) patients
BI 201335 NA high TN	ribavirin (RBV)	patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-naive (TN )patients
BI 201335 NA high TN	pegylated interferon (PegIFN) alfa-2a	patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-naive (TN )patients
BI 201335 NA high TN	BI 201335 NA high	patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-naive (TN )patients
BI 201335 NA high TN	BI 201335 NA high placebo	patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-naive (TN )patients
Placebo in Treatment Naive (TN) Patients	Placebo	-
BI 201335 NA high TE	pegylated interferon (PegIFN) alfa-2a	patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-experienced (TE) patients
BI 201335 NA high TE	ribavirin (RBV)	patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-experienced (TE) patients
BI 201335 NA high TE	BI 201335 NA high	patient to receive a capsule containing high dose of BI 201335 NA/Drug for treatment-experienced (TE) patients

Primary Outcome Measures

Name	Time	Method
Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy	4 weeks	Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy	4 weeks	Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in triple combination therapy for treatment naive patients and treatment experienced patients.
Assessment of Tolerability in Triple Combination Therapy	4 weeks	An assessment of tolerability for the safety of the triple combination therapy with BI 201335 NA, PegIFN α -2a and RBV.

Secondary Outcome Measures

Name	Time	Method
Rapid Virological Response (RVR)	4 weeks	Number of patients satisfying RVR (plasma HCV RNA level below the limit of detection (BLD) at Week 4)
Change From Baseline in HCV Viral Load	baseline and week 4	Change form baseline in HCV viral load (log10) after 4 weeks
Day 28 Virologic Response	4 weeks	Number of patients with HCV viral load reduction \>= 2 log10 at Week 4
Week 2 Virological Response (W2VR)	2 weeks	Number of patients satisfying W2VR (plasma HCV RNA (Hepatitis C Virus Ribonucleic acid) level below the limit of quantification (BLQ))
Week 4 Virological Response (W4VR)	4 weeks	Number of patients satisfying W4VR (plasma HCV RNA level below the limit of quantification (BLQ))
Early Virological Response (EVR)	12 Weeks	Number of patients with reduction \>= 2 log10 in plasma HCV RNA level at Week 12
Complete Early Virological Response (cEVR)	12 weeks	Number of patients with plasma HCV RNA level BLD at Week 12
End of Treatment Response (ETR)	48 weeks	Number of patients with plasma HCV RNA level BLD at week 48
Sustained Virologic Response (SVR)	72 weeks	Number of patients with plasma HCV RNA level BLD 24 weeks after treatment completion
Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN α-2a and RBV	44 weeks	Drug-related AEs in SOC treatment period were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.
Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN α-2a and RBV	44 weeks	Frequency of patients with possible clinically significant abnormalities or clinically significant laboratory test value changes over time in SOC period for treatment naive patients and treatment experienced patients.
Assessment of Tolerability in Standard of Care (SOC) With PegIFN α -2a and RBV	44 weeks	An assessment of tolerability for the safety of the SOC with PegIFN alfa-2a and RBV.
AUCτ,1 for BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose	Area under the curve (AUC) concentration after the first dose of BI 201335 ZW
Cmax of BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose	Maximum concentration of BI 201335 ZW after multiple oral admin. of BI 201335 NA with RBV and PegIFN alfa-2a
AUCτ,ss of BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	AUC at steady state after 4 weeks combination of the last dose
Cmax,ss of BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	Maximum concentration of BI 201335 ZW at steady state
AUCτ,1 for Ribavirin (RBV)	-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose	Area under the plasma concentration curve of RBV after the first dose of placebo or BI 201335 NA with with RBV and PegIFN alfa-2a
Cmax of RBV	-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose	Maximum Plasma concentration of RBV after multiple oral admin. of placebo with RBV and PegIFN alfa-2a
AUCτ,ss of RBV	-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose	Area under the plasma concentration curve of RBV after the multiple oral administration of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state
Cmax,ss of RBV	-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose	Maximum Plasma concentration of RBV after multiple oral admin. of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state
Tmax for BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose	Time to maximum plasma concentration (tmax) of BI 201335 ZW after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a
Tmax for RBV	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose	Time to maximum plasma concentration (tmax) of RBV after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a
Tmax, ss for BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	Time from last dosing to the maximum plasma concentration (tmax) of BI 201335 ZW after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state
Tmax, ss for RBV	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	Time to the maximum plasma concentration (tmax) of RBV after the last dose of BI 201335 NA with RBV and PegIFN alfa-2a at steady state
t1/2,ss for BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	terminal half-life of the analyte in plasma at steady state (t1/2,ss)
Cmin,ss for BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	Minimum concentration of the analyte (BI 201335 ZW) in plasma over the dosing interval at steady state
Cmin,ss for RBV	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	Minimum concentration of the analyte (RBV) in plasma over the dosing interval at steady state
Cavg for BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	average plasma concentration (Cavg) of BI 201335 ZW
Cavg for RBV	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	average plasma concentration (Cavg) of RBV
CL/F,ss for BI 201335 ZW	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	apparent clearance of the analyte (BI 201335 ZW) in plasma at steady state (CL/F,ss) following multiple oral administration

Trial Locations

Locations (3)

1220.14.003 Boehringer Ingelheim Investigational Site; 🇯🇵 Kurashiki, Okayama, Japan

1220.14.002 Boehringer Ingelheim Investigational Site; 🇯🇵 Nishinomiya, Hyogo, Japan

1220.14.001 Boehringer Ingelheim Investigational Site; 🇯🇵 Minato-ku, Tokyo, Japan