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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01525628
First received: February 1, 2012
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: midazolam
Drug: BI 201335
Drug: tenofovir
Drug: caffeine
Drug: tolbutamide
Drug: pegylated interferon
Drug: BI 207127
Drug: ribavirin
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Cmax BI 201335 [ Time Frame: Day 9, 17, 38 and 66 ] [ Designated as safety issue: No ]
  • C24hr BI 201335 [ Time Frame: Day 9, 17, 38 and 66 ] [ Designated as safety issue: No ]
  • AUC 0-24hr BI 201335 [ Time Frame: Day 9, 17, 38 and 66 ] [ Designated as safety issue: No ]
  • AUC 0-24h BI 201335 [ Time Frame: Day 9, 17, 38 and 66 ] [ Designated as safety issue: No ]
  • Cmax BI 207127 [ Time Frame: Day 9, 17, 38 and 66 ] [ Designated as safety issue: No ]
  • C6h BI 207127 [ Time Frame: Day 9, 17, 38 and 66 ] [ Designated as safety issue: No ]
  • AUC0-6h BI 207127 [ Time Frame: Day 9, 17, 38 and 66 ] [ Designated as safety issue: No ]
  • Cmax Midazolam [ Time Frame: Day 9, 17 and 66 ] [ Designated as safety issue: No ]
  • AUC 0-24h Midazolam [ Time Frame: Day 9, 17 and 66 ] [ Designated as safety issue: No ]
  • Cmax Caffeine [ Time Frame: Day 9, 17 and 66 ] [ Designated as safety issue: No ]
  • AUC 0-24h Caffeine [ Time Frame: Day 9, 17 and 66 ] [ Designated as safety issue: No ]
  • Cmax Tenofovir [ Time Frame: Day 9 and 17 ] [ Designated as safety issue: No ]
  • C24h Tenofovir [ Time Frame: Day 9 and 17 ] [ Designated as safety issue: No ]
  • AUC 0-24hr Tenofovir [ Time Frame: Day 9 and 17 ] [ Designated as safety issue: No ]
  • Cmax Raltegravir [ Time Frame: Day 9 and 17 ] [ Designated as safety issue: No ]
  • C12h Raltegravir [ Time Frame: Day 9 and 17 ] [ Designated as safety issue: No ]
  • AUC 0-12h Raltegravir [ Time Frame: Day 9 and 17 ] [ Designated as safety issue: No ]
  • C12 hr BI 207127 [ Time Frame: Day 9, 17, 38 and 66 ] [ Designated as safety issue: No ]
  • AUC 0-12 hr BI 207127 [ Time Frame: Day 9, 17, 38 and 66 ] [ Designated as safety issue: No ]
  • Cmax Tolbutamide [ Time Frame: Day 9, 17 and 66 ] [ Designated as safety issue: No ]
  • AUC 0-24 hr Tolbutamide [ Time Frame: Day 9, 17 and 66 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Sustained Virological Response [ Time Frame: 12 weeks post treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 72
Study Start Date: April 2012
Estimated Study Completion Date: October 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Effect of BI 207127 on BI 201335, the effect of BI 201335 and dual oral direct acting antiviral (DAAs) on caffeine, tolbutamide and midazolam
Drug: tolbutamide
CYP2C9 probe drug
Drug: midazolam
CYP3A probe drug
Drug: caffeine
CYP1A2 probe drug
Drug: BI 201335
HCV protease inhibitor
Drug: pegylated interferon
HCV treatment
Drug: BI 207127
HCV polymerase inhibitor
Drug: ribavirin
HCV treatment
Experimental: Group B
Effect of BI 201335 on BI 207127, the effect of BI 207127 and metabolites and dual oral DAAs on caffeine, tolbutamide and midazolam
Drug: BI 201335
HCV protease inhibitor
Drug: caffeine
CYP1A2 probe drug
Drug: tolbutamide
CYP2C9 probe drug
Drug: pegylated interferon
HCV treatment
Drug: BI 207127
HCV polymerase inhibitor
Drug: ribavirin
HCV treatment
Drug: midazolam
CYP3A probe drug
Experimental: Group C
Effect of Dual oral DAAs on tenofovir
Drug: tenofovir
nucleoside analogue
Drug: BI 207127
HCV polymerase inhibitor
Drug: ribavirin
HCV treatment
Drug: BI 201335
HCV protease inhibitor
Experimental: Group D
Effect of BI 201335 and BI 207127 at 600 mg b.i.d. on caffeine, tolbutamide and midazolam
Drug: midazolam
CYP3A probe drug
Drug: BI 201335
HCV protease inhibitor
Drug: BI 207127
HCV polymerase inhibitor
Drug: ribavirin
HCV treatment
Drug: caffeine
CYP1A2 probe drug
Drug: tolbutamide
CYP2C9 probe drug
Experimental: Group E
Effect of BI 201335 and BI 207127 on raltegravir
Drug: BI 201335
HCV protease inhibitor
Drug: ribavirin
HCV treatment
Drug: BI 207127
HCV polymerase inhibitor

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01525628

Locations
United States, California
1241.27.0006 Boehringer Ingelheim Investigational Site
La Mesa, California, United States
United States, Maryland
1241.27.0005 Boehringer Ingelheim Investigational Site
Rockville, Maryland, United States
United States, New Jersey
1241.27.0004 Boehringer Ingelheim Investigational Site
Marlton, New Jersey, United States
United States, Pennsylvania
1241.27.0003 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania, United States
United States, Utah
1241.27.0001 Boehringer Ingelheim Investigational Site
Salt Lake City, Utah, United States
Canada, British Columbia
1241.27.0700 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
1241.27.0200 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
1241.27.0600 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
1241.27.0400 Boehringer Ingelheim Investigational Site
Victoria, British Columbia, Canada
Canada, Ontario
1241.27.0100 Boehringer Ingelheim Investigational Site
London, Ontario, Canada
1241.27.0300 Boehringer Ingelheim Investigational Site
Ottawa, Ontario, Canada
Canada, Quebec
1241.27.0500 Boehringer Ingelheim Investigational Site
Montreal, Quebec, Canada
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, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01525628     History of Changes
Other Study ID Numbers: 1241.27, 2012-004102-10
Study First Received: February 1, 2012
Last Updated: October 14, 2014
Health Authority: Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Caffeine
Interferons
Midazolam
Ribavirin
Tenofovir
Tenofovir disoproxil
Tolbutamide
Adjuvants, Anesthesia
Anesthetics
Anesthetics, General
Anesthetics, Intravenous
Anti-Anxiety Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antineoplastic Agents

ClinicalTrials.gov processed this record on October 23, 2014