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

NCT01525628 | Completed Phase 1 Results

• 2 other identifiers: 1241.272012-004102-10
• Study Type: interventional
• Target: 72
• Locations: 3 countries
• Sites: 16

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.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (29)

• Cmax of Faldaprevir (BI 201335)

  Maximum concentration of an analyte in plasma

  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

  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.

• 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

  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.

• Cmax of Deleobuvir (BI 207127)

  Maximum concentration of an analyte in plasma

  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.

• C6hr of Deleobuvir (BI 207127)

  Concentration of an analyte in plasma at 6 hours

  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.

• 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

  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.

• Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

  Maximum concentration of an analyte in plasma

  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.

• C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

  Concentration of an analyte in plasma at 6 hours

  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.

• 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

  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.

• Cmax of Deleobuvir Reduction Metabolite CD 6168

  Maximum concentration of an analyte in plasma

  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.

• C6hr of Deleobuvir Reduction Metabolite CD 6168

  Concentration of an analyte in plasma at 6 hours

  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.

• 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

  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.

• Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

  Maximum concentration of an analyte in plasma

  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.

• C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

  Concentration of an analyte in plasma at 6 hours

  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.

• 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

  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.

• Cmax of Caffeine

  Maximum concentration of an analyte in plasma

  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.

  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.

• Cmax of Tolbutamide

  Maximum concentration of an analyte in plasma

  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 Tolbutamide

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

  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.

• Cmax of Midazolam

  Maximum concentration of an analyte in plasma

  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 Midazolam

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

  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.

• Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)

  Maximum concentration of an analyte in plasma

  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 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.

  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.

• Cmax of Tenofovir

  Maximum concentration of an analyte in plasma.

  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.

  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.

  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.

  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.

  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.

  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 (1)

• Number of Participants With Sustained Virological Response (SVR12)

  12 weeks post treatment

Study Arms (5)

Group A

EXPERIMENTAL

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; Drug: midazolam; Drug: caffeine; Drug: BI 201335; Drug: pegylated interferon; Drug: BI 207127; Drug: ribavirin

Group B

EXPERIMENTAL

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; Drug: caffeine; Drug: tolbutamide; Drug: pegylated interferon; Drug: BI 207127; Drug: ribavirin; Drug: midazolam

Group C

EXPERIMENTAL

Effect of Dual oral DAAs on tenofovir

Drug: tenofovir; Drug: BI 207127; Drug: ribavirin; Drug: BI 201335

Group D

EXPERIMENTAL

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

Drug: midazolam; Drug: BI 201335; Drug: BI 207127; Drug: ribavirin; Drug: caffeine; Drug: tolbutamide

Group E

EXPERIMENTAL

Effect of BI 201335 and BI 207127 on raltegravir

Drug: BI 201335; Drug: ribavirin; Drug: BI 207127

Interventions

midazolam DRUG

CYP3A probe drug

Group D

BI 201335 DRUG

HCV protease inhibitor

Group B

tenofovir DRUG

nucleoside analogue

Group C

caffeine DRUG

CYP1A2 probe drug

Group B

tolbutamide DRUG

CYP2C9 probe drug

Group B

pegylated interferon DRUG

HCV treatment

Group B

BI 207127 DRUG

HCV polymerase inhibitor

Group C

ribavirin DRUG

HCV treatment

Group B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic hepatitis C genotype 1 infection, diagnosed at least 6 months prior to screening
• Treatment naive or confirmed prior treatment relapse or partial response following treatment with interferon and ribavirin
• Age 18 to 70 years
• HCV RNA (Hepatitis C Virus RiboNucleic Acid) = 1,000 IU/mL at screening
• Liver biopsy or fibroscan to exclude cirrhosis

You may not qualify if:

• Hepatitis C Virus (HCV) infection of mixed genotype; Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV) co-infection
• Evidence of acute or chronic liver disease due to causes other than chronic HCV infection,
• Decompensated liver disease, or history of decompensated liver disease,
• Body weight \< 40 or \> 125 kg,
• Clinical evidence of significant or unstable cardiovascular disease, chronic pulmonary disease, history or evidence of retinopathy or clinically significant ophthalmological disorder
• Pre-existing psychiatric condition that could interfere with the subject's participation in and completion of the study
• Laboratory parameters disorders (thalassemia major, sickle cell anemia or glucose 6 phosphate dehydrogenase deficit)
• Hemoglobin \< 12 g/dL for women and \< 13 g/dL for men
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (16)

1241.27.0006 Boehringer Ingelheim Investigational Site

La Mesa, California, United States

Location

1241.27.0005 Boehringer Ingelheim Investigational Site

Rockville, Maryland, United States

Location

1241.27.0004 Boehringer Ingelheim Investigational Site

Marlton, New Jersey, United States

Location

1241.27.0003 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

Location

1241.27.0001 Boehringer Ingelheim Investigational Site

Salt Lake City, Utah, United States

Location

1241.27.0200 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1241.27.0600 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1241.27.0700 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1241.27.0400 Boehringer Ingelheim Investigational Site

Victoria, British Columbia, Canada

Location

1241.27.0100 Boehringer Ingelheim Investigational Site

London, Ontario, Canada

Location

1241.27.0300 Boehringer Ingelheim Investigational Site

Ottawa, Ontario, Canada

Location

1241.27.0500 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

1241.27.4907 Boehringer Ingelheim Investigational Site

Cologne, Germany

Location

1241.27.4901 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

1241.27.4903 Boehringer Ingelheim Investigational Site

Leipzig, Germany

Location

1241.27.4906 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Midazolam; faldaprevir; Tenofovir; Caffeine; Tolbutamide; deleobuvir; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Xanthines; Alkaloids; Purinones; Benzenesulfonamides; Sulfonamides; Amides; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

BI decided to stop the further development of the interferon-free combination therapy for Hepatitis C in December 2013 so the recruitment was stopped after 7 patients had entered Group E also PK analyses for Groups C to E were not performed.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2012
• First Posted: February 3, 2012
• Study Start: April 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: October 1, 2014
• Last Updated: June 10, 2016
• Results First Posted: June 10, 2016

Record last verified: 2016-05

Locations

DE (4); US (5); CA (7)