This Study Tests the Effect of Certain Medicines on the Transport of Other Medicines in the Body of Healthy Men
Condition: Healthy
Intervention: Digoxin; Furosemide; Metformin; Rosuvastatin; Verapamil; Rifampin; Cimetidine; Probenecid
Intervention description: Tablet; Oral solution; Oral solution; Film-coated tablet; Film-coated tablet; Film-coated tablet; Tablet; Tablet
Intervention MeSH terms: Metformin; Rifampin; Probenecid; Digoxin; Verapamil; Furosemide; Cimetidine; Rosuvastatin Calcium
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The primary objective of this trial is to investigate the relative bioavailabilities of
      digoxin, furosemide, metformin and rosuvastatin given as a cocktail alone and as a cocktail
      together with the following drug transporter inhibitors:

      Part 1: verapamil (P-gp) and rifampin (OATP1B1/1B3) Part 2: cimetidine (OCT2/MATE) Part 3:
      probenecid (OAT1/3) The secondary objective is to investigate other potential changes in
      pharmacokinetics (e.g. in clearance, volume of distribution, etc.) of digoxin, furosemide,
      metformin and rosuvastatin given as a cocktail alone and as a cocktail together with the
      inhibitors describe above.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male subjects according to the investigator's assessment, 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 (incl.)

          -  Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.)

          -  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)) is deviating from normal and judged 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 50 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 judged as clinically relevant by the
             investigator

          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,
             immunological or hormonal disorders

          -  Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with
             the pharmacokinetics of the trial medication (except appendectomy and 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, sulphonamides, or cardiac glycosides)

          -  Use of drugs within 30 days prior to administration of trial medication if that might
             reasonably influence the results of the trial (incl. QT/QTc interval prolongation)

          -  Participation in another trial where an investigational drug has been administered
             within 60 days prior to planned administration of trial medication, or current
             participation in another trial involving administration of investigational drug

          -  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 for males)

          -  Drug abuse or positive drug screening

          -  Blood donation of more than 100 mL within 30 days prior to administration of trial
             medication or intended donation during the trial

          -  Intention to perform excessive physical activities within one week prior to
             administration of trial medication or during the trial

          -  Inability to comply with dietary regimen of trial site

          -  Subject is assessed as unsuitable for inclusion by the investigator, for instance,
             because considered not 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 the first administration
             of trial medication until 30 days after last administration of trial medication

          -  Hypokalemia, hypomagnesemia, or hypercalcemia

          -  PQ interval greater than 220 ms in the Electrocardiogram (ECG) at screening

          -  Marked conductivity disorders (e.g. sinu-atrial blocks of II° or III°)

          -  Myopathy

          -  Hereditary galactose or fructose intolerance, lactase deficiency, or glucose-galactose
             malabsorption

          -  History of nephrolithiasis

          -  Gout or clinically relevant elevation of uric acid

          -  Creatinine clearance (according to CKD EPI formula) is lower than 80 ml/min

          -  Further exclusion criteria apply