This Study Tests the Effect of Certain Medicines on the Transport of Other Medicines in the Body of Healthy Men

NCT ID: NCT03307252

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-25
• Study Completion Date: 2018-05-02

Brief 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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Treatment Reference 1

Group Type: EXPERIMENTAL

Digoxin

Intervention Type: DRUG

Tablet

Furosemide

Intervention Type: DRUG

Oral solution

Metformin

Intervention Type: DRUG

Oral solution

Rosuvastatin

Intervention Type: DRUG

Film-coated tablet

Treatment Reference 2

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Oral solution

Treatment Reference 3

Group Type: EXPERIMENTAL

Furosemide

Intervention Type: DRUG

Oral solution

Treatment 1

Group Type: EXPERIMENTAL

Digoxin

Intervention Type: DRUG

Tablet

Furosemide

Intervention Type: DRUG

Oral solution

Metformin

Intervention Type: DRUG

Oral solution

Rosuvastatin

Intervention Type: DRUG

Film-coated tablet

Verapamil

Intervention Type: DRUG

Film-coated tablet

Treatment 2

Group Type: EXPERIMENTAL

Digoxin

Intervention Type: DRUG

Tablet

Furosemide

Intervention Type: DRUG

Oral solution

Metformin

Intervention Type: DRUG

Oral solution

Rosuvastatin

Intervention Type: DRUG

Film-coated tablet

Rifampin

Intervention Type: DRUG

Film-coated tablet

Treatment 3

Group Type: EXPERIMENTAL

Digoxin

Intervention Type: DRUG

Tablet

Furosemide

Intervention Type: DRUG

Oral solution

Metformin

Intervention Type: DRUG

Oral solution

Rosuvastatin

Intervention Type: DRUG

Film-coated tablet

Cimetidine

Intervention Type: DRUG

Tablet

Treatment 4

Group Type: EXPERIMENTAL

Digoxin

Intervention Type: DRUG

Tablet

Furosemide

Intervention Type: DRUG

Oral solution

Metformin

Intervention Type: DRUG

Oral solution

Rosuvastatin

Intervention Type: DRUG

Film-coated tablet

Probenecid

Intervention Type: DRUG

Tablet

Treatment 5

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Oral solution

Cimetidine

Intervention Type: DRUG

Tablet

Treatment 6

Group Type: EXPERIMENTAL

Furosemide

Intervention Type: DRUG

Oral solution

Probenecid

Intervention Type: DRUG

Tablet

Interventions

Digoxin

Tablet

Intervention Type: DRUG

Furosemide

Oral solution

Intervention Type: DRUG

Metformin

Oral solution

Intervention Type: DRUG

Rosuvastatin

Film-coated tablet

Intervention Type: DRUG

Verapamil

Film-coated tablet

Intervention Type: DRUG

Rifampin

Film-coated tablet

Intervention Type: DRUG

Cimetidine

Tablet

Intervention Type: DRUG

Probenecid

Tablet

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CTC North GmbH & Co. KG, Hamburg

Hamburg, , Germany

Countries

Germany

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001549-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0352-2100

Identifier Type: -

Identifier Source: org_study_id