A Study in Healthy People to Test Whether BI 730357 Affects How 4 Other Medicines (Rosuvastatin, Digoxin, Metformin, and Furosemide) Are Taken up in the Body

Healthy Clinical Trial

Official title:

The Effect of BI 730357 on the Pharmacokinetics of Rosuvastatin, Digoxin, Metformin and Furosemide Given as a Cocktail - an Open-label, Non-randomised, 2-period Fixed-sequence Trial in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04590937
• Other study ID #: 1407-0038
• Secondary ID: 2020-003097-46
• Status: Completed
• Phase: Phase 1
• Start date: October 20, 2020
• Est. completion date: January 11, 2021

Study information

• Verified date: August 2023
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of this trial is to investigate the effect of BI 730357 under steady state conditions on the pharmacokinetics of digoxin, furosemide, metformin and rosuvastatin given as a cocktail (Reference, R: cocktail alone; Test T: cocktail given under steady state conditions of BI 730357).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 11, 2021
• Est. primary completion date: January 11, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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)
• BMI of 18.5 to 29.9 kilogram per square meter (kg/m2) (inclusive)
• Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
• Male subjects, or female subjects 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 adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device
• Sexually abstinent
• 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 units per liter (U/L) and estradiol below 30 nanograms per liter (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 millimetres of Mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (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 that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
• During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2 infection
• further exclusion criteria apply

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• BI 730357
Film-coated tablet
• CRESTOR®
Film-coated tablet
• Lenoxin®
Tablet
• MetfoLiquid GeriaSan®
Oral solution
• Lasix®
Oral solution

Locations

Country	Name	City	State
Germany	Humanpharmakologisches Zentrum Biberach	Biberach

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-8, Metformin)	Area under the concentration-time curve of Metformin in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Metformin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Primary	Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-8, Rosuvastatin)	Area under the concentration-time curve of Rosuvastatin in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Rosuvastatin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Primary	Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-8, Furosemide)	Area under the concentration-time curve of Furosemide in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Furosemide in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Primary	Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-8, Digoxin)	Area under the concentration-time curve of Digoxin in plasma over the time interval from 0 extrapolated to infinity is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Digoxin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Primary	Maximum Measured Concentration of Metformin in Plasma (Cmax, Metformin)	Maximum measured concentration of Metformin in plasma is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Metformin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Primary	Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax, Rosuvastatin)	Maximum measured concentration of Rosuvastatin in plasma is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Rosuvastatin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Primary	Maximum Measured Concentration of Furosemide in Plasma (Cmax, Furosemide)	Maximum measured concentration of Furosemide in plasma is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Furosemide in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Primary	Maximum Measured Concentration of Digoxin in Plasma (Cmax, Digoxin)	Maximum measured concentration of Digoxin in plasma is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Digoxin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Secondary	Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Metformin)	Area under the concentration-time curve of Metformin in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Metformin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Secondary	Area Under the Concentration-time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Rosuvastatin)	Area under the concentration-time curve of Rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Rosuvastatin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Secondary	Area Under the Concentration-time Curve of Furosemide in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Furosemide)	Area under the concentration-time curve of Furosemide in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Furosemide in both periods plus at 143h in period 1 and at 119h and 167h in period 2.
Secondary	Area Under the Concentration-time Curve of Digoxin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz, Digoxin)	Area under the concentration-time curve of Digoxin in plasma over the time interval from 0 to the last quantifiable data point is reported. The geometric mean is actually adjusted geometric mean.	2 hours (h) before and at 20 minutes (min), 40min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 71h, 95h after administration of Digoxin in both periods plus at 143h in period 1 and at 119h and 167h in period 2.

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