Clinical trial NCT04257032: A Study in Healthy Men to Test the Influence of BI 1323495 on the Amount of the Medicines Rosuvastatin and Dabigatran in the Blood
Official title: Relative Bioavailability of Rosuvastatin (Part 1) and Dabigatran (Part 2) Given Alone and Together With BI 1323495 in Healthy Male Subjects (Open, Single-dose, Randomised, Two-period Crossover Design in Each Trial Part)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 28
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main objectives of this trial are to investigate the relative bioavailabilities of rosuvastatin (Reference 1, Part 1) and dabigatran (Reference 2, Part 2) given alone and together with BI 1323495 (Test 1, Test 2) following oral administration.


Eligibility criteria: Inclusion Criteria:

1. Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
2. Age of 18 to 55 years (inclusive)
3. BMI of 18.5 to 29.9 kg/m2 (inclusive)
4. Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
5. Subjects genotyped as Uridine 5'-diphospho-Glucuronosyltransferase-2B17 (UGT2B17) extensive metabolisers, i.e. carrying at least one functional allele of UGT2B17 gene (\*1/\*1 or \*1/\*2)

Exclusion Criteria:

1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
2. 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
3. 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)
4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
6. Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
7. Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
8. History of relevant orthostatic hypotension, fainting spells, or blackouts
9. Chronic or relevant acute infections
10. History of relevant allergy or hypersensitivity (including allergy to the trial medications or their excipients)
11. Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial or compromise the subject's safety by participation in the trial (e. g. use of any drug that could reasonably inhibit platelet aggregation or coagulation, concomitant treatment with systemic cyclosporine, ketoconazole, itraconazole and dronedarone, use of fibrates or drugs that cause QT/QTc interval prolongation (QTc: QT interval corrected for heart rate using the method of Fridericia (QTcF) or Bazett (QTcB))
12. 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
13. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
14. Inability to refrain from smoking on specified trial days
15. Alcohol abuse (consumption of more than 24 g per day)
16. Drug abuse or positive drug screening
17. Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial
18. Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
19. Inability to comply with the dietary regimen of the trial site
20. A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
21. A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
22. 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
23. Male subjects with women of childbearing 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.
24. Active clinically relevant bleeding or subjects who in the investigator's judgement are perceived as having an increased risk of bleeding, for example because of blood coagulation disorders, 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
25. For Part 1 only: known myopathy, personal or family history of hereditary muscular disorders, or history of muscular toxicity with statins or fibrate; Asian ancestry; hypothyroidism
26. Subjects with any other condition that would preclude administration of rosuvastatin or dabigatran (i.e. contraindicated as per SmPC), such as 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), prosthetic heart valves requiring anticoagulant treatment
27. During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2 infection

Primary outcomes:
measure: Part 1: Area Under the Concentration-time Curve of the Analyte (Rosuvastatin) in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: Measured within 3 hours (h) before and up to 95h after drug administration. Detailed time frame is in description section.
measure: Part 1: Maximum Measured Concentration of the Analyte (Rosuvastatin) in Plasma (Cmax)
timeFrame: Measured within 3 hours (h) before and up to 95h after drug administration. Detailed time frame is in description section.
measure: Part 2: Area Under the Concentration-time Curve of the Analyte (Dabigatran) in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: Measured within 3 hours (h) before and up to 95h after drug administration. Detailed time frame is in description section.
measure: Part 2: Maximum Measured Concentration of the Analyte (Dabigatran) in Plasma (Cmax)
timeFrame: Measured within 3 hours (h) before and up to 95h after drug administration. Detailed time frame is in description section.
Secondary outcomes:
measure: 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)
timeFrame: Measured within 3 hours (h) before and up to 95h after drug administration. Detailed time frame is in description section.
measure: 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)
timeFrame: Measured within 3 hours (h) before and up to 95h after drug administration. Detailed time frame is in description section.
Other outcomes:
Locations:
city: Biberach
country: Germany
facility: Humanpharmakologisches Zentrum Biberach
Study officials:
References: