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

Hepatitis C Clinical Trial

Official title:

Safety, Pharmacokinetics and Antiviral Effect of BI 201335 NA in HCV-1 Infected Patients Treated for 28 Days for Treatment naïve and Experienced Patients Treated in Combination With Peg Interferon Alfa-2a and Ribavirin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00947349
• Other study ID #: 1220.14
• Status: Completed
• Phase: Phase 2
• First received: July 21, 2009
• Last updated: July 3, 2015
• Start date: July 2009
• Est. completion date: August 2011

Study information

• Verified date: July 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 70 Years

Eligibility

Inclusion criteria:

• chronic HCV genotype-1;

• high viral load

Exclusion criteria:

• Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening

• Previous treatment with protease inhibitor

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Pharmacokinetics

Intervention

Drug:
• ribavirin (RBV)
ribavirin (RBV)
• pegylated interferon (PegIFN) alfa-2a
pegylated interferon (PegIFN) alfa-2a
• pegylated interferon (PegIFN) alfa-2a
pegylated interferon (PegIFN) alfa-2a
• ribavirin (RBV)
ribavirin (RBV)
• BI 201335 NA low placebo
Placebo
• pegylated interferon (PegIFN) alfa-2a
pegylated interferon (PegIFN) alfa-2a
• ribavirin (RBV)
ribavirin (RBV)
• BI 201335 NA high
BI 201335 NA high
• BI 201335 NA low
BI 201335 NA
• BI 201335 NA high placebo
placebo
• BI 201335 NA high
BI 201335 NA high
• Placebo

Locations

Country	Name	City	State
Japan	1220.14.003 Boehringer Ingelheim Investigational Site	Kurashiki, Okayama
Japan	1220.14.001 Boehringer Ingelheim Investigational Site	Minato-ku, Tokyo
Japan	1220.14.002 Boehringer Ingelheim Investigational Site	Nishinomiya, Hyogo

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Investigator Defined Drug-related Adverse Events in Triple Combination Therapy	Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.	4 weeks	No
Primary	Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Triple Combination Therapy	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.	4 weeks	No
Primary	Assessment of Tolerability in Triple Combination Therapy	An assessment of tolerability for the safety of the triple combination therapy with BI 201335 NA, PegIFN a -2a and RBV.	4 weeks	No
Secondary	Week 2 Virological Response (W2VR)	Number of patients satisfying W2VR (plasma HCV RNA (Hepatitis C Virus Ribonucleic acid) level below the limit of quantification (BLQ))	2 weeks	No
Secondary	Week 4 Virological Response (W4VR)	Number of patients satisfying W4VR (plasma HCV RNA level below the limit of quantification (BLQ))	4 weeks	No
Secondary	Rapid Virological Response (RVR)	Number of patients satisfying RVR (plasma HCV RNA level below the limit of detection (BLD) at Week 4)	4 weeks	No
Secondary	Change From Baseline in HCV Viral Load	Change form baseline in HCV viral load (log10) after 4 weeks	baseline and week 4	No
Secondary	Day 28 Virologic Response	Number of patients with HCV viral load reduction >= 2 log10 at Week 4	4 weeks	No
Secondary	Early Virological Response (EVR)	Number of patients with reduction >= 2 log10 in plasma HCV RNA level at Week 12	12 Weeks	No
Secondary	Complete Early Virological Response (cEVR)	Number of patients with plasma HCV RNA level BLD at Week 12	12 weeks	No
Secondary	End of Treatment Response (ETR)	Number of patients with plasma HCV RNA level BLD at week 48	48 weeks	No
Secondary	Sustained Virologic Response (SVR)	Number of patients with plasma HCV RNA level BLD 24 weeks after treatment completion	72 weeks	No
Secondary	Number of Participants With Investigator Defined Drug-related Adverse Events in Standard of Care (SOC) With PegIFN a-2a and RBV	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.	44 weeks	No
Secondary	Number of Patients With Possible Clinically Significant Laboratory Abnormalities in Standard of Care (SOC) With PegIFN a-2a and RBV	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.	44 weeks	No
Secondary	Assessment of Tolerability in Standard of Care (SOC) With PegIFN a -2a and RBV	An assessment of tolerability for the safety of the SOC with PegIFN alfa-2a and RBV.	44 weeks	No
Secondary	AUCt,1 for BI 201335 ZW	Area under the curve (AUC) concentration after the first dose 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	No
Secondary	Cmax of BI 201335 ZW	Maximum concentration of BI 201335 ZW after multiple oral admin. of BI 201335 NA with RBV and PegIFN alfa-2a	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose	No
Secondary	AUCt,ss of BI 201335 ZW	AUC at steady state after 4 weeks combination of the last dose	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	No
Secondary	Cmax,ss of BI 201335 ZW	Maximum concentration of BI 201335 ZW at steady state	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	No
Secondary	AUCt,1 for Ribavirin (RBV)	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	-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose	No
Secondary	Cmax of RBV	Maximum Plasma concentration of RBV after multiple oral admin. of placebo with RBV and PegIFN alfa-2a	-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the first dose	No
Secondary	AUCt,ss of RBV	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	-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose	No
Secondary	Cmax,ss of RBV	Maximum Plasma concentration of RBV after multiple oral admin. of BI 201335 NA (or placebo) with RBV and PegIFN alfa-2a at steady state	-0:10, 1,2,3,4,5,6,8,10,11:50, 23:50 hours on the last dose	No
Secondary	Tmax for BI 201335 ZW	Time to maximum plasma concentration (tmax) of BI 201335 ZW after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose	No
Secondary	Tmax for RBV	Time to maximum plasma concentration (tmax) of RBV after the first dose of BI 201335 NA with RBV and PegIFN alfa-2a	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the first dose	No
Secondary	Tmax, ss for BI 201335 ZW	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	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	No
Secondary	Tmax, ss for RBV	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	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	No
Secondary	t1/2,ss for BI 201335 ZW	terminal half-life of the analyte in plasma at steady state (t1/2,ss)	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	No
Secondary	Cmin,ss for BI 201335 ZW	Minimum concentration of the analyte (BI 201335 ZW) in plasma over the dosing interval at steady state	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	No
Secondary	Cmin,ss for RBV	Minimum concentration of the analyte (RBV) in plasma over the dosing interval at steady state	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	No
Secondary	Cavg for BI 201335 ZW	average plasma concentration (Cavg) 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	No
Secondary	Cavg for RBV	average plasma concentration (Cavg) of 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	No
Secondary	CL/F,ss for BI 201335 ZW	apparent clearance of the analyte (BI 201335 ZW) in plasma at steady state (CL/F,ss) following multiple oral administration	10 minutes before drug administration and 1 hour (h),2h,3h,4h,5h,6h,8h,10h,11:50h, 23:50h on the last dose	No

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