Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients
- Conditions
- Hepatitis C, Chronic
- Interventions
- Registration Number
- NCT01525628
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
To evaluate the drug-drug interactions between BI 201335 and BI 207127 as well as their combined effect on CYP probe drug substrates and on tenofovir and raltegravir in treatment naive or prior treatment relapse patients with chronic hepatitis C infection.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 72
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A BI 201335 Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam Group C BI 207127 Effect of Dual oral DAAs on tenofovir Group C BI 201335 Effect of Dual oral DAAs on tenofovir Group A BI 207127 Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam Group B BI 201335 Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam Group A pegylated interferon Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam Group B BI 207127 Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam Group B pegylated interferon Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam Group A caffeine Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam Group C tenofovir Effect of Dual oral DAAs on tenofovir Group E BI 207127 Effect of BI 201335 and BI 207127 on raltegravir Group D BI 201335 Effect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam Group E BI 201335 Effect of BI 201335 and BI 207127 on raltegravir Group D BI 207127 Effect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam Group A tolbutamide Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam Group A midazolam Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam Group B ribavirin Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam Group A ribavirin Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam Group B tolbutamide Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam Group B caffeine Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam Group B midazolam Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam Group C ribavirin Effect of Dual oral DAAs on tenofovir Group D midazolam Effect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam Group D tolbutamide Effect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam Group D ribavirin Effect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam Group D caffeine Effect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam Group E ribavirin Effect of BI 201335 and BI 207127 on raltegravir
- Primary Outcome Measures
Name Time Method Cmax of Faldaprevir (BI 201335) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Maximum concentration of an analyte in plasma
C24hr of Faldaprevir (BI 201335) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Concentration of an analyte in plasma at 24 hours
Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours
Cmax of Deleobuvir (BI 207127) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Maximum concentration of an analyte in plasma
C6hr of Deleobuvir (BI 207127) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Concentration of an analyte in plasma at 6 hours
AUC 0-6hr of Deleobuvir (BI 207127) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
C6hr of Deleobuvir Reduction Metabolite CD 6168 PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Concentration of an analyte in plasma at 6 hours
Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Maximum concentration of an analyte in plasma
C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Concentration of an analyte in plasma at 6 hours
AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Cmax of Deleobuvir Reduction Metabolite CD 6168 PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Maximum concentration of an analyte in plasma
AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Maximum concentration of an analyte in plasma
C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Concentration of an analyte in plasma at 6 hours
AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Cmax of Caffeine 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. Maximum concentration of an analyte in plasma
AUC 0-infinity of Caffeine 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Cmax of Tolbutamide 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. Maximum concentration of an analyte in plasma
AUC 0-infinity of Tolbutamide 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Cmax of Midazolam 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. Maximum concentration of an analyte in plasma
AUC 0-infinity of Midazolam 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. Maximum concentration of an analyte in plasma
AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Cmax of Tenofovir PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 Maximum concentration of an analyte in plasma.
C24hr of Tenofovir PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 Concentration of an analyte in plasma at 24 hours.
AUC 0-24hr of Tenofovir PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours.
Cmax of Raltegravir PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 Maximum concentration of an analyte in plasma.
AUC 0-12hr of Raltegravir PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 hours.
C12hr of Raltegravir PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 Concentration of an analyte in plasma at 12 hours.
- Secondary Outcome Measures
Name Time Method Number of Participants With Sustained Virological Response (SVR12) 12 weeks post treatment Sustained virologic response (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level \<25 IU/mL(international units per millilitre) undetectable at 12 weeks after the end of treatment. SVR12 was analyzed in a descriptive manner using frequency of participants who achieved SVR12.
Trial Locations
- Locations (16)
1241.27.0006 Boehringer Ingelheim Investigational Site
🇺🇸La Mesa, California, United States
1241.27.0003 Boehringer Ingelheim Investigational Site
🇺🇸Philadelphia, Pennsylvania, United States
1241.27.0004 Boehringer Ingelheim Investigational Site
🇺🇸Marlton, New Jersey, United States
1241.27.4903 Boehringer Ingelheim Investigational Site
🇩🇪Leipzig, Germany
1241.27.0600 Boehringer Ingelheim Investigational Site
🇨🇦Vancouver, British Columbia, Canada
1241.27.0700 Boehringer Ingelheim Investigational Site
🇨🇦Vancouver, British Columbia, Canada
1241.27.4907 Boehringer Ingelheim Investigational Site
🇩🇪Köln, Germany
1241.27.4906 Boehringer Ingelheim Investigational Site
🇩🇪Mainz, Germany
1241.27.0300 Boehringer Ingelheim Investigational Site
🇨🇦Ottawa, Ontario, Canada
1241.27.0001 Boehringer Ingelheim Investigational Site
🇺🇸Salt Lake City, Utah, United States
1241.27.0200 Boehringer Ingelheim Investigational Site
🇨🇦Vancouver, British Columbia, Canada
1241.27.0005 Boehringer Ingelheim Investigational Site
🇺🇸Rockville, Maryland, United States
1241.27.0500 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
1241.27.4901 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt am Main, Germany
1241.27.0400 Boehringer Ingelheim Investigational Site
🇨🇦Victoria, British Columbia, Canada
1241.27.0100 Boehringer Ingelheim Investigational Site
🇨🇦London, Ontario, Canada