Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients

Boehringer Ingelheim72 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatitis C, Chronic

Interventions

midazolamDRUG

CYP3A probe drug

BI 201335DRUG

HCV protease inhibitor

tenofovirDRUG

nucleoside analogue

caffeine

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. Chronic hepatitis C genotype 1 infection, diagnosed at least 6 months prior to screening 2. Treatment naive or confirmed prior treatment relapse or partial response following treatment with interferon and ribavirin 3. Age 18 to 70 years 4. HCV RNA (Hepatitis C Virus RiboNucleic Acid) = 1,000 IU/mL at screening 5. Liver biopsy or fibroscan to exclude cirrhosis Exclusion criteria: 1. Hepatitis C Virus (HCV) infection of mixed genotype; Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV) co-infection 2. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection, 3. Decompensated liver disease, or history of decompensated liver disease, 4. Body weight \< 40 or \> 125 kg, 5. Clinical evidence of significant or unstable cardiovascular disease, chronic pulmonary disease, history or evidence of retinopathy or clinically significant ophthalmological disorder 6. Pre-existing psychiatric condition that could interfere with the subject's participation in and completion of the study 7. Laboratory parameters disorders (thalassemia major, sickle cell anemia or glucose 6 phosphate dehydrogenase deficit) 8. Hemoglobin \< 12 g/dL for women and \< 13 g/dL for men 9. Patients who have been previously treated with at least one dose of any antiviral or immunomodulatory drug other than interferon alfa or ribavirin for acute or chronic HCV infection

Locations (16)

1241.27.0006 Boehringer Ingelheim Investigational Site

La Mesa, California, United States

1241.27.0005 Boehringer Ingelheim Investigational Site

Rockville, Maryland, United States

Outcomes

Primary Outcomes

Cmax of Faldaprevir (BI 201335)

Maximum concentration of an analyte in plasma

Time frame: 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.

C24hr of Faldaprevir (BI 201335)

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

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)

Maximum concentration of an analyte in plasma

C6hr of Deleobuvir (BI 207127)

Concentration of an analyte in plasma at 6 hours

AUC 0-6hr of Deleobuvir (BI 207127)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours

Data from ClinicalTrials.gov

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tolbutamideDRUG

CYP2C9 probe drug

tolbutamideDRUG

CYP2C9 probe drug

midazolamDRUG

CYP3A probe drug

caffeineDRUG

CYP1A2 probe drug

pegylated interferonDRUG

HCV treatment

BI 201335DRUG

HCV protease inhibitor

BI 201335DRUG

HCV protease inhibitor

BI 207127DRUG

HCV polymerase inhibitor

BI 207127DRUG

HCV polymerase inhibitor

BI 201335DRUG

HCV protease inhibitor

BI 207127DRUG

HCV polymerase inhibitor

ribavirinDRUG

HCV treatment

ribavirinDRUG

HCV treatment

ribavirinDRUG

HCV treatment

pegylated interferonDRUG

HCV treatment

ribavirinDRUG

HCV treatment

caffeineDRUG

CYP1A2 probe drug

tolbutamideDRUG

CYP2C9 probe drug

BI 207127DRUG

HCV polymerase inhibitor

midazolamDRUG

CYP3A probe drug

BI 201335DRUG

HCV protease inhibitor

BI 207127DRUG

HCV polymerase inhibitor

ribavirinDRUG

HCV treatment

1241.27.0004 Boehringer Ingelheim Investigational Site

Marlton, New Jersey, United States

1241.27.0003 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

1241.27.0001 Boehringer Ingelheim Investigational Site

Salt Lake City, Utah, United States

1241.27.0200 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

1241.27.0600 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

1241.27.0700 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

1241.27.0400 Boehringer Ingelheim Investigational Site

Victoria, British Columbia, Canada

1241.27.0100 Boehringer Ingelheim Investigational Site

London, Ontario, Canada

...and 6 more locations

Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

Maximum concentration of an analyte in plasma

C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

Concentration of an analyte in plasma at 6 hours

AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

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

Maximum concentration of an analyte in plasma

C6hr of Deleobuvir Reduction Metabolite CD 6168

Concentration of an analyte in plasma at 6 hours

AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168

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)

Maximum concentration of an analyte in plasma

C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

Concentration of an analyte in plasma at 6 hours

AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours

Cmax of Caffeine

Maximum concentration of an analyte in plasma

Time frame: 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.

AUC 0-infinity of Caffeine

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Cmax of Tolbutamide

Maximum concentration of an analyte in plasma

AUC 0-infinity of Tolbutamide

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Cmax of Midazolam

Maximum concentration of an analyte in plasma

AUC 0-infinity of Midazolam

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)

Maximum concentration of an analyte in plasma

AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Cmax of Tenofovir

Maximum concentration of an analyte in plasma.

Time frame: 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

C24hr of Tenofovir

Concentration of an analyte in plasma at 24 hours.

Time frame: 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

AUC 0-24hr of Tenofovir

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours.

Time frame: 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

Cmax of Raltegravir

Maximum concentration of an analyte in plasma.

Time frame: 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

C12hr of Raltegravir

Concentration of an analyte in plasma at 12 hours.

Time frame: 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

AUC 0-12hr of Raltegravir

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 hours.

Time frame: 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

Secondary Outcomes

Number of Participants With Sustained Virological Response (SVR12)

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.

Time frame: 12 weeks post treatment