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Completed

NCT Number: NCT01525628

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

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.

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Key information

Conditions

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

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

1241.27.0200 Boehringer Ingelheim Investigational Site, Vancouver, British Columbia, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

midazolam

Drug

CYP3A probe drug

BI 201335

Drug

HCV protease inhibitor

Tenofovir

Drug

nucleoside analogue

Caffeine

Drug

CYP1A2 probe drug

tolbutamide

Drug

CYP2C9 probe drug

Pegylated interferon

Drug

HCV treatment

BI 207127

Drug

HCV polymerase inhibitor

Ribavirin

Drug

HCV treatment

Primary outcomes

  1. Cmax of Faldaprevir (BI 201335)

    Time frame: 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.

    Maximum concentration of an analyte in plasma

  2. C24hr of Faldaprevir (BI 201335)

    Time frame: 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.

    Concentration of an analyte in plasma at 24 hours

  3. Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours

    Time frame: 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 of the analyte in plasma over the time interval from 0 to 24 hours

  4. Cmax of Deleobuvir (BI 207127)

    Time frame: 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.

    Maximum concentration of an analyte in plasma

  5. C6hr of Deleobuvir (BI 207127)

    Time frame: 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.

    Concentration of an analyte in plasma at 6 hours

  6. AUC 0-6hr of Deleobuvir (BI 207127)

    Time frame: 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 of the analyte in plasma over the time interval from 0 to 6 hours

  7. Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

    Time frame: 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.

    Maximum concentration of an analyte in plasma

  8. C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

    Time frame: 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.

    Concentration of an analyte in plasma at 6 hours

  9. AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

    Time frame: 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 of the analyte in plasma over the time interval from 0 to 6 hours

  10. Cmax of Deleobuvir Reduction Metabolite CD 6168

    Time frame: 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.

    Maximum concentration of an analyte in plasma

  11. C6hr of Deleobuvir Reduction Metabolite CD 6168

    Time frame: 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.

    Concentration of an analyte in plasma at 6 hours

  12. AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168

    Time frame: 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 of the analyte in plasma over the time interval from 0 to 6 hours

  13. Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

    Time frame: 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.

    Maximum concentration of an analyte in plasma

  14. C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

    Time frame: 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.

    Concentration of an analyte in plasma at 6 hours

  15. AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

    Time frame: 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 of the analyte in plasma over the time interval from 0 to 6 hours

  16. Cmax of Caffeine

    Time frame: 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.

    Maximum concentration of an analyte in plasma

  17. AUC 0-infinity of Caffeine

    Time frame: 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.

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

  18. Cmax of Tolbutamide

    Time frame: 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.

    Maximum concentration of an analyte in plasma

  19. AUC 0-infinity of Tolbutamide

    Time frame: 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.

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

  20. Cmax of Midazolam

    Time frame: 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.

    Maximum concentration of an analyte in plasma

  21. AUC 0-infinity of Midazolam

    Time frame: 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.

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

  22. Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)

    Time frame: 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.

    Maximum concentration of an analyte in plasma

  23. AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)

    Time frame: 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.

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

  24. Cmax of Tenofovir

    Time frame: 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

    Maximum concentration of an analyte in plasma.

  25. C24hr of Tenofovir

    Time frame: 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

    Concentration of an analyte in plasma at 24 hours.

  26. AUC 0-24hr of Tenofovir

    Time frame: 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

    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours.

  27. Cmax of Raltegravir

    Time frame: 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

    Maximum concentration of an analyte in plasma.

  28. C12hr of Raltegravir

    Time frame: 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

    Concentration of an analyte in plasma at 12 hours.

  29. AUC 0-12hr of Raltegravir

    Time frame: 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

    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 hours.

Secondary outcomes

  1. Number of Participants With Sustained Virological Response (SVR12)

    Time frame: 12 weeks post treatment

    Sustained virologic response (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level <25 IU/mL(international units per millilitre) undetectable at 12 weeks after the end of treatment. SVR12 was analyzed in a descriptive manner using frequency of participants who achieved SVR12.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2013
Study completion
2014
First posted
Feb 3, 2012
Registry last updated
Jun 10, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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