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

Hepatitis C, Chronic Clinical Trial

Official title:

A Multi-centre, Open Label, Parallel Group Trial to Evaluate the Pharmacokinetic Interactions Between BI 207127 (600 mg t.i.d. or 600 mg b.i.d.) and BI 201335 (120 mg q.d.) Given in Combination With Ribavirin for 24 Weeks, and Their Combined Effect on the Pharmacokinetics of Tenofovir, Raltegravir, Caffeine (the Probe Drug Substrate for CYP1A2), Tolbutamide (the Probe Drug Substrate for CYP2C9) and Midazolam (the Probe Drug Substrate for CYP3A4) in Treatment naïve Patients and Prior Treatment Relapse or Partial Responder Patients With Genotype 1 Chronic Hepatitis C Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01525628
• Other study ID #: 1241.27
• Secondary ID: 2012-004102-10
• Status: Completed
• Phase: Phase 1
• First received: February 1, 2012
• Last updated: February 4, 2015
• Start date: April 2012
• Est. completion date: October 2014

Study information

• Verified date: February 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• midazolam
CYP3A probe drug
• BI 201335
HCV protease inhibitor
• tenofovir
nucleoside analogue
• caffeine
CYP1A2 probe drug
• tolbutamide
CYP2C9 probe drug
• tolbutamide
CYP2C9 probe drug
• midazolam
CYP3A probe drug
• caffeine
CYP1A2 probe drug
• pegylated interferon
HCV treatment
• BI 201335
HCV protease inhibitor
• BI 201335
HCV protease inhibitor
• BI 207127
HCV polymerase inhibitor
• BI 207127
HCV polymerase inhibitor
• BI 201335
HCV protease inhibitor
• BI 207127
HCV polymerase inhibitor
• ribavirin
HCV treatment
• ribavirin
HCV treatment
• ribavirin
HCV treatment
• pegylated interferon
HCV treatment
• ribavirin
HCV treatment
• caffeine
CYP1A2 probe drug
• tolbutamide
CYP2C9 probe drug
• BI 207127
HCV polymerase inhibitor
• midazolam
CYP3A probe drug
• BI 201335
HCV protease inhibitor
• BI 207127
HCV polymerase inhibitor
• ribavirin
HCV treatment

Locations

Country	Name	City	State
Canada	1241.27.0100 Boehringer Ingelheim Investigational Site	London	Ontario
Canada	1241.27.0500 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1241.27.0300 Boehringer Ingelheim Investigational Site	Ottawa	Ontario
Canada	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
Germany	1241.27.4901 Boehringer Ingelheim Investigational Site	Frankfurt am Main
Germany	1241.27.4907 Boehringer Ingelheim Investigational Site	Köln
Germany	1241.27.4903 Boehringer Ingelheim Investigational Site	Leipzig
Germany	1241.27.4906 Boehringer Ingelheim Investigational Site	Mainz
United States	1241.27.0006 Boehringer Ingelheim Investigational Site	La Mesa	California
United States	1241.27.0004 Boehringer Ingelheim Investigational Site	Marlton	New Jersey
United States	1241.27.0003 Boehringer Ingelheim Investigational Site	Philadelphia	Pennsylvania
United States	1241.27.0005 Boehringer Ingelheim Investigational Site	Rockville	Maryland
United States	1241.27.0001 Boehringer Ingelheim Investigational Site	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax BI 201335		Day 9, 17, 38 and 66	No
Primary	C24hr BI 201335		Day 9, 17, 38 and 66	No
Primary	AUC 0-24hr BI 201335		Day 9, 17, 38 and 66	No
Primary	AUC 0-24h BI 201335		Day 9, 17, 38 and 66	No
Primary	Cmax BI 207127		Day 9, 17, 38 and 66	No
Primary	C6h BI 207127		Day 9, 17, 38 and 66	No
Primary	AUC0-6h BI 207127		Day 9, 17, 38 and 66	No
Primary	Cmax Midazolam		Day 9, 17 and 66	No
Primary	AUC 0-24h Midazolam		Day 9, 17 and 66	No
Primary	Cmax Caffeine		Day 9, 17 and 66	No
Primary	AUC 0-24h Caffeine		Day 9, 17 and 66	No
Primary	Cmax Tenofovir		Day 9 and 17	No
Primary	C24h Tenofovir		Day 9 and 17	No
Primary	AUC 0-24hr Tenofovir		Day 9 and 17	No
Primary	Cmax Raltegravir		Day 9 and 17	No
Primary	C12h Raltegravir		Day 9 and 17	No
Primary	AUC 0-12h Raltegravir		Day 9 and 17	No
Primary	C12 hr BI 207127		Day 9, 17, 38 and 66	No
Primary	AUC 0-12 hr BI 207127		Day 9, 17, 38 and 66	No
Primary	Cmax Tolbutamide		Day 9, 17 and 66	No
Primary	AUC 0-24 hr Tolbutamide		Day 9, 17 and 66	No
Secondary	Sustained Virological Response		12 weeks post treatment	No