Clinical trial NCT04679948: A Study in Healthy People to Test Whether BI 730357 Influences the Amount of Caffeine, Warfarin, Omeprazole, and Midazolam in the Blood
Official title: The Effect of Multiple Doses of BI 730357 on the Single Dose Pharmacokinetics of Caffeine, Warfarin, Omeprazole and Midazolam Administered Orally as a Cocktail in Healthy Subjects (an Open-label, Two-period Fixed Sequence Design Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2020-12-22
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Two Periods (Period 1 and Period 2) for each participant.
Primary purpose: TREATMENT

Brief summary: The trial will be performed to assess the influence of BI 730357 on the pharmacokinetics of caffeine, warfarin, omeprazole and midazolam.


Eligibility criteria: Inclusion Criteria:

* Healthy subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
* Age of 18 to 55 years (inclusive)
* Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
* Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation
* Either male subject, or female subject who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:

  * Use of non-hormonal intrauterine device plus condom for birth control
  * A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
  * Surgically sterilised (including hysterectomy or bilateral tubal occlusion)
  * Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)

Exclusion Criteria:

* Any finding in the medical examination (including BP, PR, or ECG) deviating from normal and assessed as clinically relevant by the investigator
* Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm
* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
* Any evidence of a concomitant disease assessed as clinically relevant by the investigator
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
* Cholecystectomy or other surgery of the gastrointestinal tract (except appendectomy or simple hernia repair) that could interfere with the pharmacokinetics (PK) of the trial medication
* Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
* History of relevant orthostatic hypotension, fainting spells, or blackouts Further inclusion exclusion criteria apply

Primary outcomes:
measure: Area Under the Concentration-time Curve of Caffeine in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Caffeine)
timeFrame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods.
measure: Maximum Measured Concentration of the Caffeine in Plasma (Cmax, Caffeine)
timeFrame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods.
measure: Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, S-warfarin)
timeFrame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods.
measure: Maximum Measured Concentration of the S-warfarin in Plasma (Cmax, S-warfarin)
timeFrame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods.
measure: Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Omeprazole)
timeFrame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods.
measure: Maximum Measured Concentration of Omeprazole in Plasma (Cmax, Omeprazole)
timeFrame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods.
measure: Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Midazolam)
timeFrame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods.
measure: Maximum Measured Concentration of Midazolam in Plasma (Cmax, Midazolam)
timeFrame: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods.
Secondary outcomes:
Other outcomes:
Locations:
city: Biberach
country: Germany
facility: Humanpharmakologisches Zentrum Biberach
Study officials:
References: