Clinical trial NCT01528735: This Trial Evaluates Safety, Pharmacokinetic Profile and Anti-viral Response of BI 207127 and BI 201335 for Patients With Chronic Hepatitis C
Official title: An Open-label, Ascending Dose, Phase II Study to Evaluate Tolerability, Safety, Antiviral Activity, and Pharmacokinetics of BI 207127 NA in Combination With BI 201335 NA and Ribavirin for 8 Weeks in Treatment-naïve Japanese Patients With Genotype 1chronic Hepatitis C Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-02-08
Enrollment: 25
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Drug-related Adverse Events
timeFrame: From first dose of study medication until 30 days after last dose of study medication, up to 199 days
Secondary outcomes:
measure: Percentage of Participants With Virological Response at Week 4
timeFrame: 4 weeks
measure: Percentage of Participants With Virological Response at Week 8
timeFrame: 8 weeks
measure: Maximum Measured Concentration (Cmax) of Deleobuvir
timeFrame: 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
measure: Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir
timeFrame: 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
measure: Area Under the Curve (AUC) of Deleobuvir
timeFrame: 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
measure: Maximum Measured Concentration (Cmax) of Faldaprevir
timeFrame: 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
measure: Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir
timeFrame: 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
measure: Area Under the Curve (AUC) of Faldaprevir
timeFrame: 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
measure: Maximum Measured Concentration (Cmax) of BI 208333
timeFrame: 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
measure: Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333
timeFrame: 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
measure: Area Under the Curve (AUC) of BI 208333
timeFrame: 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
measure: Maximum Measured Concentration (Cmax) of CD 6168
timeFrame: 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
measure: Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168
timeFrame: 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
measure: Area Under the Curve (AUC) of CD 6168
timeFrame: 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
measure: Maximum Measured Concentration (Cmax) of CD 6168-AG
timeFrame: 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
measure: Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG
timeFrame: 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
measure: Area Under the Curve (AUC) of CD 6168-AG
timeFrame: 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
measure: Maximum Measured Concentration (Cmax) of RBV
timeFrame: 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
measure: Time From Last Dosing to the Maximum Concentration (Tmax) of RBV
timeFrame: 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
measure: Area Under the Curve (AUC) of RBV
timeFrame: 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
measure: Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir
timeFrame: 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
measure: AUC Accumulation Ratio of Deleobuvir
timeFrame: 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
measure: Mean Residence Time (MRTpo,ss) of Deleobuvir
timeFrame: 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
measure: Apparent Clearance (CL/F,ss) of Deleobuvir
timeFrame: 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
measure: Predose Measured Concentration of Deleobuvir
timeFrame: 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
measure: Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir
timeFrame: 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
measure: AUC Accumulation Ratio of Faldaprevir
timeFrame: 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
measure: Mean Residence Time (MRTpo,ss) of Faldaprevir
timeFrame: 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
measure: Apparent Clearance (CL/F,ss) of Faldaprevir
timeFrame: 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
measure: Predose Measured Concentration of Faldaprevir
timeFrame: 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
measure: Cmax Accumulation Ratio of BI 208333
timeFrame: 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
measure: AUC Accumulation Ratio of BI 208333
timeFrame: 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
measure: Mean Residence Time (MRTpo,ss) of BI 208333
timeFrame: 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
measure: Predose Measured Concentration of BI 208333
timeFrame: 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
measure: Cmax Accumulation Ratio of CD 6168
timeFrame: 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
measure: AUC Accumulation Ratio of CD 6168
timeFrame: 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
measure: Mean Residence Time (MRTpo,ss) of CD 6168
timeFrame: 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
measure: Predose Measured Concentration of CD 6168
timeFrame: 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
measure: Cmax Accumulation Ratio of CD 6168-AG
timeFrame: 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
measure: AUC Accumulation Ratio of CD 6168-AG
timeFrame: 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
measure: Mean Residence Time (MRTpo,ss) of CD 6168-AG
timeFrame: 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
measure: Predose Measured Concentration of CD 6168-AG
timeFrame: 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
measure: AUC Accumulation Ratio of RBV
timeFrame: 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
measure: Cmax Accumulation Ratio (RA,Cmax,57) of RBV
timeFrame: 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
measure: Mean Residence Time (MRTpo,ss) of RBV
timeFrame: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on day 57
measure: Predose Measured Concentration of RBV
timeFrame: 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
Other outcomes:
Locations:
city: Kofu, Yamanashi
country: Japan
facility: 1241.25.002 Boehringer Ingelheim Investigational Site
city: Kurashiki, Okayama
country: Japan
facility: 1241.25.005 Boehringer Ingelheim Investigational Site
city: Nagoya, Aichi
country: Japan
facility: 1241.25.003 Boehringer Ingelheim Investigational Site
city: Nishinomiya, Hyogo
country: Japan
facility: 1241.25.004 Boehringer Ingelheim Investigational Site
city: Omura, Nagasaki
country: Japan
facility: 1241.25.001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Yatsuhashi H, Kodani N, Ugai H, Omata M. Open-label phase 2 study of faldaprevir, deleobuvir and ribavirin in Japanese treatment-naive patients with chronic hepatitis C virus genotype 1 infection. Hepatol Res. 2016 Mar;46(3):E189-93. doi: 10.1111/hepr.12535. Epub 2015 Jun 18.