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

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Hepatitis C, Chronic

Treatments: Drug: BI 207127; Drug: ribavirin; Drug: tolbutamide; Drug: pegylated interferon; Drug: BI 201335; Drug: tenofovir; Drug: caffeine; Drug: midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT01525628

2012-004102-10 (EudraCT Number)

1241.27

Details and patient eligibility

About

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.

Enrollment: 72 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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72 participants in 5 patient groups

Group A

Experimental group

Description:

Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam

Treatment:

Drug: caffeine

Drug: caffeine

Drug: pegylated interferon

Drug: BI 207127

Drug: ribavirin

Drug: tolbutamide

Drug: BI 207127

Drug: pegylated interferon

Drug: ribavirin

Drug: BI 201335

Drug: caffeine

Drug: BI 201335

Drug: BI 201335

Drug: ribavirin

Drug: BI 201335

Drug: BI 201335

Drug: ribavirin

Drug: BI 207127

Drug: tolbutamide

Drug: tolbutamide

Drug: BI 207127

Drug: ribavirin

Drug: BI 207127

Drug: midazolam

Drug: midazolam

Drug: midazolam

Group B

Experimental group

Description:

Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam

Treatment:

Drug: caffeine

Drug: caffeine

Drug: pegylated interferon

Drug: BI 207127

Drug: ribavirin

Drug: tolbutamide

Drug: BI 207127

Drug: pegylated interferon

Drug: ribavirin

Drug: BI 201335

Drug: caffeine

Drug: BI 201335

Drug: BI 201335

Drug: ribavirin

Drug: BI 201335

Drug: BI 201335

Drug: ribavirin

Drug: BI 207127

Drug: tolbutamide

Drug: tolbutamide

Drug: BI 207127

Drug: ribavirin

Drug: BI 207127

Drug: midazolam

Drug: midazolam

Drug: midazolam

Group C

Experimental group

Description:

Effect of Dual oral DAAs on tenofovir

Treatment:

Drug: BI 207127

Drug: ribavirin

Drug: BI 207127

Drug: ribavirin

Drug: BI 201335

Drug: BI 201335

Drug: BI 201335

Drug: ribavirin

Drug: BI 201335

Drug: BI 201335

Drug: tenofovir

Drug: ribavirin

Drug: BI 207127

Drug: BI 207127

Drug: ribavirin

Drug: BI 207127

Group D

Experimental group

Description:

Effect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam

Treatment:

Drug: caffeine

Drug: caffeine

Drug: BI 207127

Drug: ribavirin

Drug: tolbutamide

Drug: BI 207127

Drug: ribavirin

Drug: BI 201335

Drug: caffeine

Drug: BI 201335

Drug: BI 201335

Drug: ribavirin

Drug: BI 201335

Drug: BI 201335

Drug: ribavirin

Drug: BI 207127

Drug: tolbutamide

Drug: tolbutamide

Drug: BI 207127

Drug: ribavirin

Drug: BI 207127

Drug: midazolam

Drug: midazolam

Drug: midazolam

Group E

Experimental group

Description:

Effect of BI 201335 and BI 207127 on raltegravir

Treatment:

Drug: BI 207127

Drug: ribavirin

Drug: BI 207127

Drug: ribavirin

Drug: BI 201335

Drug: BI 201335

Drug: BI 201335

Drug: ribavirin

Drug: BI 201335

Drug: BI 201335

Drug: ribavirin

Drug: BI 207127

Drug: BI 207127

Drug: ribavirin

Drug: BI 207127