A Study in Healthy Men to Test the Influence of BI 1358894 on the Amount of the Medicines Rosuvastatin and Dabigatran in the Blood

Relative Bioavailability of Rosuvastatin (Part 1) and Dabigatran (Part 2) Given Alone and Together With BI 1358894 in Healthy Male Subjects (Open, Single-dose, Fixed Sequence, Two-period Crossover Design in Each Trial Part)

The main objective of this trial is to investigate the relative bioavailability of rosuvastatin (Reference 1, Part 1) and dabigatran (Reference 2, Part 2) given alone and together with BI 1358894 (Test 1, Test 2) following oral administration.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rosuvastatin; Drug: BI 1358894; Device: Dabigatran etexilate

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany, 88397
    • Humanpharmakologisches Zentrum Biberach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

• Healthy male 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/m^2 (inclusive)
• Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

• Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (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 (including positive or missing faecal occult blood test in Part 2, retest allowed)
• 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
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation)
• Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Inability to refrain from smoking on specified trial days
• Alcohol abuse (consumption of more than 24 g per day)
• Drug abuse or positive drug screening
• Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial
• Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
• Inability to comply with the dietary regimen of the trial site
• A marked prolongation of QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
• A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
• Male subjects with women of child bearing potential (WOCBP) partner who are unwilling to use male contraception (condom or sexual abstinence) from time point of administration of trial medication until 30 days thereafter. Sperm donation is not allowed from the time point of drug administration until 30 days thereafter.
• Known hypersensitivity to rosuvastatin or dabigatran
• Active liver disease including elevations of serum transaminases exceeding 2 times the upper limit of normal
• Moderate or severe renal impairment (creatinine clearance < 60 ml/min based on estimated Glomerular Filtration Rate (GFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
• Known myopathy
• Concomitant treatment with systemic cyclosporine, ketoconazole, itraconazole and dronedarone or use of fibrates
• Hypothyroidism
• Personal or family history of hereditary muscular disorders
• History of muscular toxicity with another statin or fibrate
• Asian ancestry
• Known active bleeding
• Concomitant treatment with other anticoagulants (e.g. unfractionated heparin, low molecular weight heparins, heparin derivatives, oral anticoagulants)
• Prosthetic heart valves
• Subjects who in the investigator's judgement are perceived as having an increased risk of bleeding, for example because of: current or recent gastrointestinal ulceration, presence of malignant neoplasms, recent brain or spinal injury, recent brain / spinal/ ophthalmic surgery, recent intracranial hemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms, major intraspinal or intracerebral vascular abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Reference 1 followed by Test 1; Reference 1 - Rosuvastatin. Test 1 - Rosuvastatin + BI 1358894	Drug: Rosuvastatin; Tablet; Drug: BI 1358894; Tablet
Experimental: Part 2: Reference 2 followed by Test 2; Reference 2 - Dabigatran etexilate. Test 2 - Dabigatran etexilate + BI 1358894	Drug: BI 1358894; Tablet; Device: Dabigatran etexilate; Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part1: Area Under the Concentration-time Curve of the Analyte (Rosuvastatin) in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of the analyte (rosuvastatin) in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Rosuvastatin (Reference 1) was measured within 3 hours (h) before drug administration and 1h, 2h, 3h, 3h 30 minutes (min) 4h, 4h 30min, 5h, 5h 30min, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h and 96h after drug administration. Rosuvastatin + BI 1358894 (Test 1) was measured within 3 hours before drug administration and 1h, 2h, 3h, 3h 30 minutes (min) 4h, 4h 30min, 5h, 5h 30min, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h and 96h after drug administration.	Rosuvastatin (R1): within 3 hours before and up to 96 hours after drug administration. Rosuvastatin + BI 1358894 (1): within 3 hours before and up to 96 hours after drug administration. Detailed timeframe is provided in the description section.
Part 1: Maximum Measured Concentration of the Analyte (Rosuvastatin) in Plasma (Cmax)	Maximum measured concentration of the analyte (rosuvastatin) in Plasma (Cmax). Rosuvastatin (Reference 1) was measured within 3 hours (h) before drug administration and 1h, 2h, 3h, 3h 30 minutes (min) 4h, 4h 30min, 5h, 5h 30min, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h and 96h after drug administration. Rosuvastatin + BI 1358894 (Test 1) was measured within 3 hours before drug administration and 1h, 2h, 3h, 3h 30 minutes (min) 4h, 4h 30min, 5h, 5h 30min, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h and 96h after drug administration.	Rosuvastatin (R1): within 3 hours before and up to 96 hours after drug administration. Rosuvastatin + BI 1358894 (T1): within 3 hours before and up to 96 hours after drug administration. Detailed timeframe is provided in the description section.
Part 2: Area Under the Concentration-time Curve of the Analyte (Dabigatran) in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of the analyte (dabigatran) in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Dabigatran (Reference 2) was measured within 3 hours (h) before drug administration and 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration. Dabigatran + BI 1358894 (Test 2) was measured within 3h before drug administration and 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration.	Dabigatran (2): within 3 hours before and up to 72 hours after drug administration. Dabigatran + BI 1358894 (T2): within 3 hours before and up to 72 hours after drug administration. Detailed time frame is in description section.
Part 2: Maximum Measured Concentration of the Analyte (Dabigatran) in Plasma (Cmax)	Maximum measured concentration of the analyte (dabigatran) in plasma (Cmax). Dabigatran (Reference 2) was measured within 3 hours (h) before drug administration and 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration. Dabigatran + BI 1358894 (Test 2) was measured within 3h before drug administration and 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration.	Dabigatran (R2): within 3 hours before and up to 72 hours after drug administration. Dabigatran + BI 1358894 (T2): within 3 hours before and up to 72 hours after drug administration. Detailed time frame is in description section.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Area Under the Concentration-time Curve of the Analyte (Rosuvastatin) in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	Area under the concentration-time curve of the analyte (rosuvastatin) in plasma over the time interval from 0 to the last quantifiable data Point (AUC0-tz). Rosuvastatin (Reference 1) was measured within 3 hours (h) before drug administration and 1h, 2h, 3h, 3h 30 minutes (min) 4h, 4h 30min, 5h, 5h 30min, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h and 96h after drug administration. Rosuvastatin + BI 1358894 (Test1) was measured within 3 hours before drug administration and 1h, 2h, 3h, 3h 30 minutes (min) 4h, 4h 30min, 5h, 5h 30min, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h and 96h after drug administration.	Rosuvastatin (R1): within 3 hours before and up to 96 hours after drug administration. Rosuvastatin + BI 1358894 (T1): within 3 hours before and up to 96 hours after drug administration. .Detailed time frame is in description section.
Part 2: Area Under the Concentration-time Curve of the Analyte (Dabigatran) in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	Area under the concentration-time curve of the analyte (dabigatran) in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Dabigatran (Reference 2) was measured within 3h before drug administration and 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration. Dabigatran + BI 1358894 (Test 2) was measured within 3h before drug administration and 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration.	Dabigatran (R2): within 3 hours before and up to 72 hours after drug administration. Dabigatran + BI 1358894 (T2): within 3 hours before and up to 72 hours after drug administration. Detailed time frame is in description section.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2019
• Primary Completion (Actual): December 10, 2019
• Study Completion (Actual): December 10, 2019

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 20, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Antimetabolites; Anticoagulants; Antithrombins; Serine Proteinase Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Dabigatran; Rosuvastatin Calcium
• Other Study ID Numbers: 1402-0009; 2019-002763-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: http://trials.boehringer-ingelheim.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No