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CompletedNCT02182336Updated Jul 18, 2014

Effects of BI 201335 NA on Cytochrome P450 and P-glycoprotein Activity Using a Probe Drug Cocktail in Healthy Volunteers

A Phase 1 interventional study of BI 201335 NA and Caffeine in Healthy, sponsored by Boehringer Ingelheim. Completed. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-07-18.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
23
Allocation
Not applicable
Ages
18 Years to 55 Years
Sex
All
01

Study summary

The objective of this trial was to quantify the effect of oral single-dose (480 mg) and steady-state BI 201335 NA (240 mg BID) on intestinal and hepatic cytochrome P450 (CYP) and P-glycoprotein (P-gp) probe drugs as a means of predicting drug interactions. The AUCs for the probe drugs caffeine, warfarin, omeprazole, dextromethorphan, midazolam, and digoxin were assessed.

02

Conditions studied

  • Healthy
03

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

  • Healthy males and female subjects age ≥18 to ≤55 years and according to the following criteria:

    • Complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead EKG (electrocardiogram)(including determination of QTcB, and QtcF intervals), and clinical laboratory tests; all with acceptable findings
  • Weighing at least 50 kg, and BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
  • Volunteers must not leave the research unit, during the days of over-night stays, which include the periods from evening of Day-1 to morning of Day 5, and evening of Day 9 to morning of Day 24
  • Volunteers must be willing to complete all study-related activities

Exclusion criteria

Exclusion Criteria:

  • Any finding of the medical examination (including blood pressure, pulse rate and EKG) deviating from normal and of clinical relevance, as assessed by the investigator
  • Active diseases of the gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, musculoskeletal, immunologic, rheumatologic, hormonal, neurological system, cancer, or bleeding disorders that require current medical treatment, may be unstable, or may be exacerbated by participation in the study
  • Any evidence of a clinically relevant concomitant disease, which is not defined in the exclusion criteria 2 above, including but not limited to relevant chronic or acute infection
  • Surgery of the gastrointestinal tract (except appendectomy and endoscopic removal of colon polyps)
  • History or presence of allergy to any of the study drugs (e.g., BI 201335 NA, caffeine, warfarin, vitamin K, omeprazole, dextromethorphan, digoxin, midazolam, omeprazole) or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation
  • Concomitant drugs, nutraceuticals, and herbal remedies that in the opinion of the investigator (in consultation with the BI medical monitor or pharmacokineticist), would interfere with either the absorption, distribution or metabolism of BI 201335 NA, or other study drugs
  • Use of drugs, which might reasonably influence the results of the trial or that prolong the QT/QTc interval within 30 days prior to screening until trial completion
  • Use of any investigational drug within 30 days prior to enrollment; or the planned usage of any investigational drug during the course of the current study
  • Smoking (>10 cigarettes or >3 cigars or >3 pipes/day)
  • Inability to abstain from alcohol from day of screening to 7 days after last study drug administration.
  • Drug abuse
  • Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
  • Excessive physical activities (within one week prior to administration or during the trial
  • Any laboratory value outside the reference range that is of clinical relevance at screening, according to the judgment of the investigator, and in consultation with the clinical monitor
  • Known elevated liver enzymes in past with any compound (experimental or marketed)
  • Concomitant administration of any food product known to alter P450 enzyme or P-gp activity such as grapefruit juice, Seville oranges, St. John's Wort
  • Concomitant administration of any drug that could affect bleeding (e.g., aspirin, clopidogrel, ticlopidine, warfarin in addition to the studied warfarin dose, heparin, low-molecular weight heparin)
  • Concomitant administration of oral contraceptives (may be included with 7-day washout period)
  • Inadequate venous access
  • Renal or hepatic insufficiency
  • A marked baseline prolongation of QT/QTc interval e.g., repeated demonstration of a QTcF, or QTcB interval >450 ms)
  • Infection with hepatitis B (HBV), or hepatitis C virus (HCV), defined as either being hepatitis B surface antigen and /or hepatitis B core antibody positive, or hepatitis C antibody positive)
  • Positive Enzyme-linked immunosorbent assay (ELISA) for Human Immunodeficiency Virus (HIV)-1 or HIV-2
  • Fasting screening laboratory testing with direct bilirubin within the normal range and elevated total bilirubin, defined as 30% above the upper limit of normal

  • For female subjects:

    • Pregnancy or planning to become pregnant within 2 months of study completion
    • Positive pregnancy test at screening visit
    • No adequate contraception, e.g., sterilisation, IUD (intrauterine device), have not been using a barrier method of contraception for at least 3 months prior to participation in the study
    • Are not willing or are unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial
    • Lactation period with active breastfeeding from time of screening to 30 days after end of trial visit
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
23 participants (actual)

Study arms

  • Experimental
    BI 201335 NA

    Drug: BI 201335 NA · Drug: Caffeine · Drug: Warfarin sodium · Drug: Vitamin K · Drug: Omeprazole · Drug: Dextromethorphan hydrobromide · Drug: Midazolam HCl solution · Drug: Midazolam HCl oral syrup · Drug: Digoxin

Interventions

  • DrugBI 201335 NA

    1. 480 mg BI 201335 NA in the morning, 240 mg BI 201335 NA in the evening of day 10 2. 240 mg BI 201335 NA bid from day 11 to 23

  • DrugCaffeine

    days 1, 10 and 19

  • DrugWarfarin sodium

    days 1, 10 and 19

  • DrugVitamin K

    days 1, 10 and 19

  • DrugOmeprazole

    days 1, 10 and 19

  • DrugDextromethorphan hydrobromide

    days 1, 10 and 19

  • DrugMidazolam HCl solution

    Days 3 and 21

  • DrugMidazolam HCl oral syrup

    days 1, 10 and 19

  • DrugDigoxin

    Days 2 and 20

06

What researchers measure

Primary outcomes

  1. Area under the curve (AUC) 0-24h of caffeine

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours after treatment on days 1, 10 and 19

  2. AUC0-120h of Warfarin

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours after treatment on days 1, 10 and 19

  3. AUC0-24h of Omeprazole

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours after treatment on days 1, 10 and 19

  4. AUC0-24h of Dextromethorphan

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours after treatment on days 1, 10 and 19

  5. AUC0-24h of Midazolam IV

    Time frame: Pre-dose and 0.08, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours after treatment on days 3 and 21

  6. AUC0-24h of Midazolam oral

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours after treatment on days 1, 10 and 19

  7. AUC0-96h of Digoxin

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours after treatment on days 2 and 20

Secondary outcomes

  1. AUC of caffeine

    Time frame: Baseline and day 1, day 1 and day 19

  2. Cmax (Maximum Plasma Concentration after a single dose) of caffeine

    Time frame: Baseline and day 1, baseline and day 19

  3. Ct (Plasma concentration at a given time t after a single dose) of caffeine

    Time frame: Baseline and day 1, baseline and day 19

  4. tmax (Time of Maximum Concentration after a single dose) of caffeine

    Time frame: Baseline and day 1, baseline and day 19

  5. CL/F (Oral Clearance after a single dose) of caffeine

    Time frame: Baseline and day1, baseline and day 19

  6. t1/2 (Apparent Terminal Half-Life) of caffeine

    Time frame: Baseline and day 1, baseline and day 19

  7. AUC of Warfarin

    Time frame: Baseline and day 1, day 1 and day 19

  8. Cmax of Warfarin

    Time frame: Baseline and day 1, day 1 and day 19

  9. Ct of Warfarin

    Time frame: Baseline and day 1, day 1 and day 19

  10. tmax of Warfarin

    Time frame: Baseline and day 1, day 1 and day 19

  11. CL/F of Warfarin

    Time frame: Baseline and day 1, day 1 and day 19

  12. t1/2 of Warfarin

    Time frame: Baseline and day 1, day 1 and day 19

  13. AUC of Omeprazole

    Time frame: Baseline and day 1, day 1 and day 19

  14. Cmax of Omeprazole

    Time frame: Baseline and day 1, day 1 and day 19

  15. Ct of Omeprazole

    Time frame: Baseline and day 1, day 1 and day 19

  16. tmax of Omeprazole

    Time frame: Baseline and day 1, day 1 and day 19

  17. CL/F of Omeprazole

    Time frame: Baseline and day 1, day 1 and day 19

  18. t1/2 of Omeprazole

    Time frame: Baseline and day 1, day 1 and day 19

  19. AUC of Dextromethorphan

    Time frame: Baseline and day 1, day 1 and day 19

  20. Cmax of Dextromethorphan

    Time frame: Baseline and day 1, day 1 and day 19

  21. Ct of Dextromethorphan

    Time frame: Baseline and day 1, day 1 and day 19

  22. tmax of Dextromethorphan

    Time frame: Baseline and day 1, day 1 and day 19

  23. CL/F of Dextromethorphan

    Time frame: Baseline and day 1, day 1 and day 19

  24. t1/2 of Dextromethorphan

    Time frame: Baseline and day 1, day 1 and day 19

  25. AUC of Midazolam IV

    Time frame: Baseline and day 1, day 1 and day 19

  26. Cmax of Midazolam IV

    Time frame: Baseline and day 1, day 1 and day 19

  27. Ct of Midazolam IV

    Time frame: Baseline and day 1, day 1 and day 19

  28. tmax of Midazolam IV

    Time frame: Baseline and day 1, day 1 and day 19

  29. CL/F of Midazolam IV

    Time frame: Baseline and day 1, day 1 and day 19

  30. t1/2 of Midazolam IV

    Time frame: Baseline and day 1, day 1 and day 19

  31. AUC of Midazolam oral

    Time frame: Baseline and day 1, baseline and day 19

  32. Cmax of Midazolam oral

    Time frame: Baseline and day 1, baseline and day 19

  33. Ct of Midazolam oral

    Time frame: Baseline and day 1, baseline and day 19

  34. tmax of Midazolam oral

    Time frame: Baseline and day 1, baseline and day 19

  35. CL/F of Midazolam oral

    Time frame: Baseline and day 1, baseline and day 19

  36. t1/2 of Midazolam oral

    Time frame: Baseline and day 1, baseline and day 19

  37. AUC of Digoxin

    Time frame: Baseline and day 1, baseline and day 19

  38. Cmax of Digoxin

    Time frame: Baseline and day 1, baseline and day 19

  39. Ct of Digoxin

    Time frame: Baseline and day 1, baseline and day 19

  40. tmax of Digoxin

    Time frame: Baseline and day 1, baseline and day 19

  41. CL/F of Digoxin

    Time frame: Baseline and day 1, baseline and day 19

  42. t1/2 of Digoxin

    Time frame: Baseline and day 1, baseline and day 19

  43. AUCτ,N (Uniform Dosing Interval τ Following the Nth Dose) of BI201335 NA

    Time frame: Day 10

  44. AUCτ,ss,N of BI201335 NA

    Time frame: Day 19

  45. Cmax,N of BI 201335 NA

    Time frame: Day 10

  46. Cmax,ss,N of BI 201335 NA

    Time frame: Day 19

  47. tmax,N of BI 201335 NA

    Time frame: Day 10

  48. tmax,ss,N of BI 201335 NA

    Time frame: Day 19

  49. Cmin,N of BI 201335 NA

    Time frame: Day 10

  50. Cmin,ss,N of BI 201335 NA

    Time frame: Day 19

  51. CL/F,ss,N of BI 201335 NA

    Time frame: Day 19

  52. Urinary metabolic ratios of the analyte of first-day and steady state

    Time frame: up to day 19

07

Study locations

No study locations are listed for this record.

08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 18, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT02182336
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Jul 8, 2014
Start date
Jun 2008
Primary completion
Sep 2008
Last update
Jul 18, 2014
View the source record on ClinicalTrials.gov ↗

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