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

NCT03307252 | Completed Phase 1 Results

• 2 other identifiers: 0352-21002017-001549-29
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (8)

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1)

  AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. Geometric mean (gMean) presented here is an adjusted gMean and standard error (SE) presented is a geometric SE (gSE).

  Samples were taken within 0:20 hour:minutes (hh:mm) prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1)

  AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1)

  AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1)

  AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)

  Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)

  Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)

  Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)

  Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

Secondary Outcomes (4)

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T1 vs. R1)

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1)

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1)

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1)

  Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.

Study Arms (9)

Treatment Reference 1

EXPERIMENTAL

Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin

Treatment Reference 2

EXPERIMENTAL

Drug: Metformin

Treatment Reference 3

EXPERIMENTAL

Drug: Furosemide

Treatment 1

EXPERIMENTAL

Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin; Drug: Verapamil

Treatment 2

EXPERIMENTAL

Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin; Drug: Rifampin

Treatment 3

EXPERIMENTAL

Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin; Drug: Cimetidine

Treatment 4

EXPERIMENTAL

Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin; Drug: Probenecid

Treatment 5

EXPERIMENTAL

Drug: Metformin; Drug: Cimetidine

Treatment 6

EXPERIMENTAL

Drug: Furosemide; Drug: Probenecid

Interventions

Digoxin DRUG

Tablet

Treatment 1; Treatment 2; Treatment 3; Treatment 4; Treatment Reference 1

Furosemide DRUG

Oral solution

Treatment 1; Treatment 2; Treatment 3; Treatment 4; Treatment 6; Treatment Reference 1; Treatment Reference 3

Metformin DRUG

Oral solution

Treatment 1; Treatment 2; Treatment 3; Treatment 4; Treatment 5; Treatment Reference 1; Treatment Reference 2

Rosuvastatin DRUG

Film-coated tablet

Treatment 1; Treatment 2; Treatment 3; Treatment 4; Treatment Reference 1

Verapamil DRUG

Film-coated tablet

Treatment 1

Rifampin DRUG

Film-coated tablet

Treatment 2

Cimetidine DRUG

Tablet

Treatment 3; Treatment 5

Probenecid DRUG

Tablet

Treatment 4; Treatment 6

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

CTC North GmbH & Co. KG, Hamburg

Hamburg, 20251, Germany

Location

MeSH Terms

Interventions

Digoxin; Furosemide; Metformin; Rosuvastatin Calcium; Verapamil; Rifampin; Cimetidine; Probenecid

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Biguanides; Guanidines; Amidines; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenethylamines; Ethylamines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Imidazoles; Azoles

Results Point of Contact

• Title: Boehringer Ingelheim, Call Centre
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: October 11, 2017
• Study Start: October 25, 2017
• Primary Completion: May 2, 2018
• Study Completion: May 2, 2018
• Last Updated: November 7, 2023
• Results First Posted: July 12, 2019

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)