Clinical trial NCT01525628: Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C, Chronic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-02-03
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Cmax of Faldaprevir (BI 201335)
timeFrame: 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.
measure: C24hr of Faldaprevir (BI 201335)
timeFrame: 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.
measure: Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours
timeFrame: 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.
measure: Cmax of Deleobuvir (BI 207127)
timeFrame: 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.
measure: C6hr of Deleobuvir (BI 207127)
timeFrame: 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.
measure: AUC 0-6hr of Deleobuvir (BI 207127)
timeFrame: 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.
measure: Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
timeFrame: 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.
measure: C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
timeFrame: 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.
measure: AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
timeFrame: 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.
measure: Cmax of Deleobuvir Reduction Metabolite CD 6168
timeFrame: 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.
measure: C6hr of Deleobuvir Reduction Metabolite CD 6168
timeFrame: 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.
measure: AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168
timeFrame: 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.
measure: Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
timeFrame: 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.
measure: C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
timeFrame: 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.
measure: AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
timeFrame: 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.
measure: Cmax of Caffeine
timeFrame: 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.
measure: AUC 0-infinity of Caffeine
timeFrame: 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.
measure: Cmax of Tolbutamide
timeFrame: 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.
measure: AUC 0-infinity of Tolbutamide
timeFrame: 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.
measure: Cmax of Midazolam
timeFrame: 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.
measure: AUC 0-infinity of Midazolam
timeFrame: 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.
measure: Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)
timeFrame: 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.
measure: AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)
timeFrame: 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.
measure: Cmax of Tenofovir
timeFrame: 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
measure: C24hr of Tenofovir
timeFrame: 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
measure: AUC 0-24hr of Tenofovir
timeFrame: 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
measure: Cmax of Raltegravir
timeFrame: 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
measure: C12hr of Raltegravir
timeFrame: 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
measure: AUC 0-12hr of Raltegravir
timeFrame: 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:
measure: Number of Participants With Sustained Virological Response (SVR12)
timeFrame: 12 weeks post treatment
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: 1241.27.0006 Boehringer Ingelheim Investigational Site
state: California
city: Rockville
country: United States
facility: 1241.27.0005 Boehringer Ingelheim Investigational Site
state: Maryland
city: Marlton
country: United States
facility: 1241.27.0004 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Philadelphia
country: United States
facility: 1241.27.0003 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Salt Lake City
country: United States
facility: 1241.27.0001 Boehringer Ingelheim Investigational Site
state: Utah
city: Vancouver
country: Canada
facility: 1241.27.0200 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1241.27.0600 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1241.27.0700 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: 1241.27.0400 Boehringer Ingelheim Investigational Site
state: British Columbia
city: London
country: Canada
facility: 1241.27.0100 Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: 1241.27.0300 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1241.27.0500 Boehringer Ingelheim Investigational Site
state: Quebec
city: Frankfurt am Main
country: Germany
facility: 1241.27.4901 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 1241.27.4907 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 1241.27.4903 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1241.27.4906 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: