HealthyPhase 1NCT03307252

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

A Phase 1 study testing Digoxin, Furosemide and Metformin in people with Healthy, run by Boehringer Ingelheim at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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)… Read more about this study

Who is it for?: Ages 18 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Digoxin, Furosemide and Metformin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 45 participants
Where: 1 siteGermany
Study dates: 25 Oct 2017to 2 May 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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)

Show all 30Show fewer

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

Trial locations and contacts

1 site in 1 country.

Germany1 site

CTC North GmbH & Co. KG, Hamburg
Hamburg, 20251

Other trials in Germany

About this study

Official title: The Effect of Potent Inhibitors of Drug Transporters (Verapamil, Rifampin, Cimetidine, Probenecid) on Pharmacokinetics of a Transporter Probe Drug Cocktail Consisting of Digoxin, Furosemide, Metformin and Rosuvastatin (an Open-label, Randomised, Crossover Trial in Three Parts)

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
Being tested: Digoxin, Furosemide, Metformin, Rosuvastatin, Verapamil

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DigoxinDrug
Tablet
FurosemideDrug
Oral solution
MetforminDrug
Oral solution
RosuvastatinDrug
Film-coated tablet
VerapamilDrug
Film-coated tablet
RifampinDrug
Film-coated tablet
CimetidineDrug
Tablet
ProbenecidDrug
Tablet

Study groups in NCT03307252
Study group	Role	What they receive
Treatment Reference 1	Experimental	Not described Receives: Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin
Treatment Reference 2	Experimental	Not described Receives: Drug: Metformin
Treatment Reference 3	Experimental	Not described Receives: Drug: Furosemide
Treatment 1	Experimental	Not described Receives: Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin; Drug: Verapamil
Treatment 2	Experimental	Not described Receives: Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin; Drug: Rifampin
Treatment 3	Experimental	Not described Receives: Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin; Drug: Cimetidine
Treatment 4	Experimental	Not described Receives: Drug: Digoxin; Drug: Furosemide; Drug: Metformin; Drug: Rosuvastatin; Drug: Probenecid
Treatment 5	Experimental	Not described Receives: Drug: Metformin; Drug: Cimetidine
Treatment 6	Experimental	Not described Receives: Drug: Furosemide; Drug: Probenecid

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
AUC0-∞, 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 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
Measured: 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)
AUC0-∞, 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 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
Measured: 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)
AUC0-∞, 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 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
Measured: 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)
AUC0-∞, 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 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Oct 20172 May 2018

First posted11 Oct 2017
Study start25 Oct 2017
Primary completion2 May 2018
Study completion2 May 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 45 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03307252
Sponsor's protocol ID: 0352-2100
Other IDs: 2017-001549-29, 2017
Status last verified: Oct 2023
First submitted: 6 Oct 2017
Last updated: 7 Nov 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 1
Dynamic Magnetic Resonance Imaging of Human Subarachnoid Space Using Intrathecal Gadolinium Contrast
Healthy Volunteers
RecruitingObservational study
Survey to Determine Incarcerated Persons' Views on Surrogate Decision Making
Healthy Volunteers
Active, not recruitingPhase 1
A Study to Learn How Different Amounts of the Study Medicine Called PF-07985631 Are Tolerated and Act in the Body of Healthy Adults
Healthy
Not yet recruitingObservational study
Collection and Distribution of Blood Components From Healthy Donors for In Vitro Research Use
Blood Donors, Apheresis
Recruiting
Metabolic Impact of VLCPUFA-Rich Fish Oil: A Clinical Study on Omega-3 Index Enhancement in Healthy Individuals
Fatty Acids, Omega-3, Fish Oils

All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effect of Potent Inhibitors of Drug Transporters (Verapamil, Rifampin, Cimetidine, Probenecid) on Pharmacokinetics of a Transporter Probe Drug Cocktail Consisting of Digoxin, Furosemide, Metformin and Rosuvastatin (an Open-label, Randomised, Crossover Trial in Three Parts)
ClinicalTrials.gov ID: NCT03307252
Acronym / sponsor ID: 0352-2100
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 45 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 25 Oct 2017 (actual)
Primary completion: 2 May 2018 (actual)
Study completion: 2 May 2018 (actual)
First posted: 11 Oct 2017 (actual)
Results: Posted 12 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 9

Arm	Type	Receives
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

Who may qualify

Ages: 18 to 55 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (30 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DigoxinTablet	Drug	Treatment 1, Treatment 2, Treatment 3, Treatment 4, Treatment Reference 1
FurosemideOral solution	Drug	Treatment 1, Treatment 2, Treatment 3, Treatment 4, Treatment 6, Treatment Reference 1, Treatment Reference 3
MetforminOral solution	Drug	Treatment 1, Treatment 2, Treatment 3, Treatment 4, Treatment 5, Treatment Reference 1, Treatment Reference 2
RosuvastatinFilm-coated tablet	Drug	Treatment 1, Treatment 2, Treatment 3, Treatment 4, Treatment Reference 1
VerapamilFilm-coated tablet	Drug	Treatment 1
RifampinFilm-coated tablet	Drug	Treatment 2
CimetidineTablet	Drug	Treatment 3, Treatment 5
ProbenecidTablet	Drug	Treatment 4, Treatment 6

Primary outcome

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)
Time frame: 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.
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).
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)
Time frame: 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.
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.
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)
Time frame: 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.
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.
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)
Time frame: 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.
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.
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)
Time frame: 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.
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.
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)
Time frame: 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.
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.
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)
Time frame: 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.
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.
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)
Time frame: 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.
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.

4 secondary outcomes

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

Results and safety

Results posted to the registry on 12 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)	4	4
(Verapamil + R1)/ (Rifampin + R1)/ R1	4	4
(Rifampin + R1)/ R1/ (Verapamil + R1)	4	4
R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)	0	0
Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)	0	0
(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin	0	0
(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1	0	0
R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)	0	0
Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)	0	0
(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide	0	0
(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1	0	0

Primary outcome: 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)

Time frame: 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.. Geometric mean (Standard Error). Unit: Nanomole*hour/litre (nmol*h/L)

Measure	Verapamil + R1 (T1) n = 12	Cocktail (R1) n = 12
Digoxin	13.71 (1.10)	13.61 (1.10)
Furosemide	165.80 (1.06)	176.85 (1.06)
Metformin	1126.22 (1.05)	1357.34 (1.05)
Rosuvastatin	98.98 (1.11)	87.29 (1.11)

Verapamil + R1 (T1) vs Cocktail (R1): Adjusted geometric mean (gMean) ratio: 100.70 (90% CI 88.84 to 114.15), ANOVA
Verapamil + R1 (T1) vs Cocktail (R1): Adjusted gMean ratio: 93.76 (90% CI 86.12 to 102.06), ANOVA
Verapamil + R1 (T1) vs Cocktail (R1): Adjusted gMean Ratio: 82.97 (90% CI 76.96 to 89.46), ANOVA

Population analysed: Pharmacokinetic (PK) parameter analysis set (PKS): All subjects in the TS providing at least 1 primary or secondary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.

Primary outcome: 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)

Time frame: 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.. Geometric mean (Standard Error). Unit: Nanomole*hour/litre (nmol*h/L)

Measure	Rifampin + R1 (T2) n = 12	Cocktail (R1) n = 12
Digoxin	17.89 (1.10)	13.61 (1.10)
Furosemide	211.82 (1.06)	176.85 (1.06)
Metformin	1473.38 (1.05)	1357.34 (1.05)
Rosuvastatin	303.81 (1.11)	87.29 (1.11)

Rifampin + R1 (T2) vs Cocktail (R1): Adjusted geometric mean (gMean) ratio: 131.41 (90% CI 115.93 to 148.97), ANOVA
Rifampin + R1 (T2) vs Cocktail (R1): Adjusted gMean ratio: 119.78 (90% CI 110.03 to 130.39), ANOVA
Rifampin + R1 (T2) vs Cocktail (R1): Adjusted gMean Ratio: 108.55 (90% CI 100.68 to 117.03), ANOVA

Population analysed: PKS

Primary outcome: 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)

Measure	Cimetidine + R1 (T3) n = 15	Cocktail (R1) n = 13
Digoxin	19.03 (1.07)	15.15 (1.07)
Furosemide	196.39 (1.05)	194.05 (1.05)
Metformin	2006.60 (1.06)	1532.41 (1.07)
Rosuvastatin	139.54 (1.13)	129.90 (1.13)

Cimetidine + R1 (T3) vs Cocktail (R1): Adjusted geometric mean (gMean) ratio: 125.61 (90% CI 113.99 to 138.43), ANOVA
Cimetidine + R1 (T3) vs Cocktail (R1): Adjusted gMean ratio: 101.21 (90% CI 94.59 to 108.30), ANOVA
Cimetidine + R1 (T3) vs Cocktail (R1): Adjusted gMean Ratio: 130.94 (90% CI 119.82 to 143.10), ANOVA

Population analysed: PKS

Primary outcome: 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)

Measure	Probenecid + R1 (T4) n = 15	Cocktail (R1) n = 16
Digoxin	14.44 (1.08)	13.52 (1.08)
Furosemide	483.38 (1.08)	177.96 (1.07)
Metformin	1331.83 (1.08)	1321.20 (1.08)
Rosuvastatin	238.16 (1.10)	106.69 (1.10)

Probenecid + R1 (T4) vs Cocktail (R1): Adjusted geometric mean (gMean) ratio: 106.78 (90% CI 96.51 to 118.15), ANOVA
Probenecid + R1 (T4) vs Cocktail (R1): Adjusted gMean ratio: 271.63 (90% CI 246.74 to 299.03), ANOVA
Probenecid + R1 (T4) vs Cocktail (R1): Adjusted gMean Ratio: 100.80 (90% CI 94.62 to 107.39), ANOVA

Population analysed: PKS

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cocktail (R1)	0 of 42 (0%)	5 of 42 (11.9%)	0 of 42
Verapamil + R1 (T1)	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
Rifampin + R1 (T2)	0 of 12 (0%)	2 of 12 (16.7%)	0 of 12
Metformin (R2)	0 of 16 (0%)	7 of 16 (43.8%)	0 of 16
Cimetidine + R1 (T3)	0 of 17 (0%)	7 of 17 (41.2%)	0 of 17
Cimetidine + R2 (T5)	0 of 17 (0%)	7 of 17 (41.2%)	0 of 17
Furosemide (R3)	0 of 16 (0%)	4 of 16 (25%)	0 of 16
Probenecid + R1 (T4)	0 of 16 (0%)	4 of 16 (25%)	0 of 16
Probenecid + R3 (T6)	0 of 15 (0%)	3 of 15 (20%)	0 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Related trials for Healthy

Not yet recruitingPhase 1
Dynamic Magnetic Resonance Imaging of Human Subarachnoid Space Using Intrathecal Gadolinium Contrast
Healthy Volunteers
RecruitingObservational study
Survey to Determine Incarcerated Persons' Views on Surrogate Decision Making
Healthy Volunteers
Active, not recruitingPhase 1
A Study to Learn How Different Amounts of the Study Medicine Called PF-07985631 Are Tolerated and Act in the Body of Healthy Adults
Healthy
Not yet recruitingObservational study
Collection and Distribution of Blood Components From Healthy Donors for In Vitro Research Use
Blood Donors, Apheresis
Recruiting
Metabolic Impact of VLCPUFA-Rich Fish Oil: A Clinical Study on Omega-3 Index Enhancement in Healthy Individuals
Fatty Acids, Omega-3, Fish Oils

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Digoxin, Furosemide and Metformin in people with Healthy, run by Boehringer Ingelheim at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: 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.). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03307252.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.