Transporter Cocktail Mutual Interaction

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Rosuvastatin; Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Metformin hydrochloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT02854527

352.2096

2016-001893-14 (EudraCT Number)

Details and patient eligibility

About

Main objective is to investigate mutual pharmacokinetic drug-drug interactions of digoxin, furosemide, metformin, and rosuvastatin when given all together as a cocktail

Enrollment: 30 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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 and local legislation

Exclusion criteria

• Any finding in the medical examination (including BP, PR or 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 that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation (corrected Q-T interval)
• 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 30 g per day)
• 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

In addition, the following trial-specific exclusion criteria apply:

• Hypokalemia, hypomagnesemia, or hypercalcemia
• PQ ( (time between the onset of the P wave (atrial activity) and the QRS complex (ventricular activity)) interval greater than 220 ms in the ECG at screening
• Myopathy
• Hereditary galactose or fructose intolerance, lactase deficiency, or glucose-galactose malabsorption

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 5 patient groups

R1 (Reference 1) Digoxin

Experimental group

Description:

1 tablet (0.25 mg) digoxin as single dose

Treatment:

Drug: Digoxin

Drug: Digoxin

R2 Furosemide

Experimental group

Description:

0.1 mL (1 mg) furosemide oral solution as single dose

Treatment:

Drug: Furosemide

Drug: Furosemide

R3 Metformin hydrochloride

Experimental group

Description:

0.1 mL (10 mg) metformin oral solution as single dose

Treatment:

Drug: Metformin

R4 Rosuvastatin

Experimental group

Description:

1 tablet (10 mg) rosuvastatin as single dose

Treatment:

Drug: Rosuvastatin

Drug: Rosuvastatin

T (Test)

Experimental group

Description:

1 tablet (0.25 mg) digoxin, 0.1 mL (1 mg) furosemide oral solution, 0.1 mL (10 mg) metformin oral solution, and 1 tablet (10 mg) rosuvastatin, all together as a single dose ('cocktail')

Treatment:

Drug: Metformin hydrochloride

Drug: Rosuvastatin

Drug: Furosemide

Drug: Digoxin

Drug: Furosemide

Drug: Rosuvastatin

Drug: Digoxin