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CompletedNCT03307252Updated Nov 7, 2023Results posted

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

A Phase 1 interventional study of Digoxin and Furosemide in Healthy, sponsored by Boehringer Ingelheim. Completed at 1 site in Germany. Open to male participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-11-07.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
45
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
Male
01

Study 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.

02

Conditions studied

  • Healthy
03

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

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

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
04

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
45 participants (actual)

Study arms

  • Experimental
    Treatment Reference 1

    Drug: Digoxin · Drug: Furosemide · Drug: Metformin · Drug: Rosuvastatin

  • Experimental
    Treatment Reference 2

    Drug: Metformin

  • Experimental
    Treatment Reference 3

    Drug: Furosemide

  • Experimental
    Treatment 1

    Drug: Digoxin · Drug: Furosemide · Drug: Metformin · Drug: Rosuvastatin · Drug: Verapamil

  • Experimental
    Treatment 2

    Drug: Digoxin · Drug: Furosemide · Drug: Metformin · Drug: Rosuvastatin · Drug: Rifampin

  • Experimental
    Treatment 3

    Drug: Digoxin · Drug: Furosemide · Drug: Metformin · Drug: Rosuvastatin · Drug: Cimetidine

  • Experimental
    Treatment 4

    Drug: Digoxin · Drug: Furosemide · Drug: Metformin · Drug: Rosuvastatin · Drug: Probenecid

  • Experimental
    Treatment 5

    Drug: Metformin · Drug: Cimetidine

  • Experimental
    Treatment 6

    Drug: Furosemide · Drug: Probenecid

Interventions

  • DrugDigoxin

    Tablet

  • DrugFurosemide

    Oral solution

  • DrugMetformin

    Oral solution

  • DrugRosuvastatin

    Film-coated tablet

  • DrugVerapamil

    Film-coated tablet

  • DrugRifampin

    Film-coated tablet

  • DrugCimetidine

    Tablet

  • DrugProbenecid

    Tablet

05

What researchers measure

Primary outcomes

  1. 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).

    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.

  2. 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.

    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.

  3. 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.

    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.

  4. 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.

    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.

  5. 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.

    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.

  6. 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.

    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.

  7. 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.

    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.

  8. 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.

    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.

Secondary outcomes

  1. 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.

    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.

  2. 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.

    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.

  3. 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.

    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.

  4. 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.

    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.

06

Results

Posted Jul 12, 2019

Participant flow

The trial consisted of 3 parts investigating different drug transporter inhibitors. All parts of the trial were performed in healthy male participants in a randomised, open-label, three-way (Part 1) or four-way (Part 2 and 3) crossover design.

Part 1, Period 1
Participant flow — Part 1, Period 1
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started44400000000
Completed44400000000
Not completed00000000000
Part 1, Washout Period 1 (13 Days)
Participant flow — Part 1, Washout Period 1 (13 Days)
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started44400000000
Completed44400000000
Not completed00000000000
Part 1, Period 2
Participant flow — Part 1, Period 2
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started44400000000
Completed44400000000
Not completed00000000000
Part 1, Washout Period 2 (13 Days)
Participant flow — Part 1, Washout Period 2 (13 Days)
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started44400000000
Completed44400000000
Not completed00000000000
Part 1, Period 3
Participant flow — Part 1, Period 3
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started44400000000
Completed44400000000
Not completed00000000000
Part 2, Period 1
Participant flow — Part 2, Period 1
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00044450000
Completed00044350000
Not completed00000100000
Withdrew: Treatment not received00000100000
Part 2, Washout Period 1 (7 Days)
Participant flow — Part 2, Washout Period 1 (7 Days)
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00044350000
Completed00044350000
Not completed00000000000
Part 2, Period 2
Participant flow — Part 2, Period 2
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00044350000
Completed00044350000
Not completed00000000000
Part 2, Washout Period 2 (7 Days)
Participant flow — Part 2, Washout Period 2 (7 Days)
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00044350000
Completed00044350000
Not completed00000000000
Part 2, Period 3
Participant flow — Part 2, Period 3
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00044350000
Completed00043350000
Not completed00001000000
Withdrew: Other than listed00001000000
Part 2, Washout Period 3 (7 Days)
Participant flow — Part 2, Washout Period 3 (7 Days)
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00043350000
Completed00043340000
Not completed00000010000
Part 2, Period 4
Participant flow — Part 2, Period 4
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00043350000
Completed00043340000
Not completed00000010000
Withdrew: Other than listed00000010000
Part 3, Period 1
Participant flow — Part 3, Period 1
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00000004444
Completed00000004444
Not completed00000000000
Part 3, Washout Period 1 (7 Days)
Participant flow — Part 3, Washout Period 1 (7 Days)
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00000004444
Completed00000004444
Not completed00000000000
Part 3, Period 2
Participant flow — Part 3, Period 2
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00000004444
Completed00000004444
Not completed00000000000
Part 3, Washout Period 2 (7 Days)
Participant flow — Part 3, Washout Period 2 (7 Days)
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00000004444
Completed00000004444
Not completed00000000000
Part 3, Period 3
Participant flow — Part 3, Period 3
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00000004444
Completed00000004444
Not completed00000000000
Part 3, Washout Period 3 (7 Days)
Participant flow — Part 3, Washout Period 3 (7 Days)
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00000004444
Completed00000004443
Not completed00000000001
Withdrew: Treatment not received due to ae00000000001
Part 3, Period 4
Participant flow — Part 3, Period 4
MilestoneCocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
Started00000004443
Completed00000004443
Not completed00000000000

Outcome measures

PrimaryArea 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).

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.
Reported as:
Geometric mean · Nanomole*hour/litre (nmol*h/L)
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)
Nanomole*hour/litre (nmol*h/L)Verapamil + R1 (T1)Cocktail (R1)
Digoxin13.71 ± 1.1013.61 ± 1.10
Furosemide165.80 ± 1.06176.85 ± 1.06
Metformin1126.22 ± 1.051357.34 ± 1.05
Rosuvastatin98.98 ± 1.1187.29 ± 1.11
Statistical analysis
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted geometric mean (gmean) ratio: 100.70 · 90% CI 88.84 to 114.15Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 93.76 · 90% CI 86.12 to 102.06Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 82.97 · 90% CI 76.96 to 89.46Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 113.40 · 90% CI 97.62 to 131.72Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
PrimaryArea 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.

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.
Reported as:
Geometric mean · Nanomole*hour/litre (nmol*h/L)
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)
Nanomole*hour/litre (nmol*h/L)Rifampin + R1 (T2)Cocktail (R1)
Digoxin17.89 ± 1.1013.61 ± 1.10
Furosemide211.82 ± 1.06176.85 ± 1.06
Metformin1473.38 ± 1.051357.34 ± 1.05
Rosuvastatin303.81 ± 1.1187.29 ± 1.11
Statistical analysis
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted geometric mean (gmean) ratio: 131.41 · 90% CI 115.93 to 148.97Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 119.78 · 90% CI 110.03 to 130.39Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 108.55 · 90% CI 100.68 to 117.03Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 348.06 · 90% CI 299.64 to 404.31Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
PrimaryArea 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.

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.
Reported as:
Geometric mean · Nanomole*hour/litre (nmol*h/L)
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)
Nanomole*hour/litre (nmol*h/L)Cimetidine + R1 (T3)Cocktail (R1)
Digoxin19.03 ± 1.0715.15 ± 1.07
Furosemide196.39 ± 1.05194.05 ± 1.05
Metformin2006.60 ± 1.061532.41 ± 1.07
Rosuvastatin139.54 ± 1.13129.90 ± 1.13
Statistical analysis
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted geometric mean (gmean) ratio: 125.61 · 90% CI 113.99 to 138.43Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 101.21 · 90% CI 94.59 to 108.30Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 130.94 · 90% CI 119.82 to 143.10Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 107.42 · 90% CI 97.57 to 118.27Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.
PrimaryArea 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.

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.
Reported as:
Geometric mean · Nanomole*hour/litre (nmol*h/L)
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)
Nanomole*hour/litre (nmol*h/L)Probenecid + R1 (T4)Cocktail (R1)
Digoxin14.44 ± 1.0813.52 ± 1.08
Furosemide483.38 ± 1.08177.96 ± 1.07
Metformin1331.83 ± 1.081321.20 ± 1.08
Rosuvastatin238.16 ± 1.10106.69 ± 1.10
Statistical analysis
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted geometric mean (gmean) ratio: 106.78 · 90% CI 96.51 to 118.15Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 271.63 · 90% CI 246.74 to 299.03Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 100.80 · 90% CI 94.62 to 107.39Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 223.24 · 90% CI 203.79 to 244.55Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
PrimaryMaximum 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.

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.
Reported as:
Geometric mean · Nanomole/ litre (nmol/ L)
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)
Nanomole/ litre (nmol/ L)Verapamil + R1 (T1)Cocktail (R1)
Digoxin1.42 ± 1.091.17 ± 1.09
Furosemide84.32 ± 1.0688.59 ± 1.06
Metformin179.45 ± 1.04223.78 ± 1.04
Rosuvastatin7.90 ± 1.146.84 ± 1.14
Statistical analysis
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted geometric mean (gmean) ratio: 121.64 · 90% CI 100.43 to 147.33Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 95.18 · 90% CI 83.03 to 109.11Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 80.19 · 90% CI 73.01 to 88.08Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 115.39 · 90% CI 93.80 to 141.94Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
PrimaryMaximum 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.

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.
Reported as:
Geometric mean · Nanomole/ litre (nmol/ L)
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)
Nanomole/ litre (nmol/ L)Rifampin + R1 (T2)Cocktail (R1)
Digoxin2.55 ± 1.091.17 ± 1.09
Furosemide119.66 ± 1.0688.59 ± 1.06
Metformin251.32 ± 1.04223.78 ± 1.04
Rosuvastatin77.00 ± 1.146.84 ± 1.14
Statistical analysis
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted geometric mean (gmean) ratio: 218.26 · 90% CI 180.19 to 264.36Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 135.07 · 90% CI 117.83 to 154.84Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 112.31 · 90% CI 102.26 to 123.35Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 1125.10 · 90% CI 914.63 to 1384.00Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
PrimaryMaximum 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.

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.
Reported as:
Geometric mean · Nanomole/ litre (nmol/ L)
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)
Nanomole/ litre (nmol/ L)Cimetidine + R1 (T3)Cocktail (R1)
Digoxin1.65 ± 1.071.35 ± 1.08
Furosemide97.69 ± 1.0893.23 ± 1.08
Metformin316.83 ± 1.07258.33 ± 1.08
Rosuvastatin13.21 ± 1.1511.30 ± 1.15
Statistical analysis
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted geometric mean (gmean) ratio: 218.26 · 90% CI 180.19 to 264.36Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 104.78 · 90% CI 89.97 to 122.03Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 122.65 · 90% CI 107.68 to 139.69Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 116.88 · 90% CI 105.07 to 130.03Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.
PrimaryMaximum 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.

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.
Reported as:
Geometric mean · Nanomole/ litre (nmol/ L)
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)
Nanomole/ litre (nmol/ L)Probenecid + R1 (T4)Cocktail (R1)
Digoxin1.13 ± 1.071.30 ± 1.07
Furosemide110.64 ± 1.0790.00 ± 1.07
Metformin246.78 ± 1.12243.49 ± 1.12
Rosuvastatin43.29 ± 1.1110.11 ± 1.10
Statistical analysis
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted geometric mean (gmean) ratio: 87.07 · 90% CI 76.08 to 99.64Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 122.94 · 90% CI 110.25 to 137.09Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 101.35 · 90% CI 93.65 to 109.70Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 428.23 · 90% CI 359.78 to 509.70Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
SecondaryArea 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.

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.
Reported as:
Geometric mean · Nanomole*hour/litre (nmol*h/L)
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T1 vs. R1)
Nanomole*hour/litre (nmol*h/L)Verapamil + R1 (T1)Cocktail (R1)
Furosemide176.44 ± 1.06191.29 ± 1.06
Metformin1147.23 ± 1.051365.85 ± 1.05
Rosuvastatin116.80 ± 1.1094.14 ± 1.10
Statistical analysis
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 92.24 · 90% CI 85.28 to 99.76Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 83.99 · 90% CI 78.32 to 90.08Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
  • Verapamil + R1 (T1) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 124.06 · 90% CI 105.11 to 146.43Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.
SecondaryArea 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.

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.
Reported as:
Geometric mean · Nanomole*hour/litre (nmol*h/L)
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1)
Nanomole*hour/litre (nmol*h/L)Rifampin + R1 (T2)Cocktail (R1)
Furosemide215.63 ± 1.06191.29 ± 1.06
Metformin1482.76 ± 1.051365.85 ± 1.05
Rosuvastatin320.72 ± 1.1094.14 ± 1.10
Statistical analysis
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 112.73 · 90% CI 104.23 to 121.92Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 108.56 · 90% CI 101.22 to 116.43Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
  • Rifampin + R1 (T2) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 340.67 · 90% CI 288.63 to 402.10Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.
SecondaryArea 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.

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.
Reported as:
Geometric mean · Nanomole*hour/litre (nmol*h/L)
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1)
Nanomole*hour/litre (nmol*h/L)Cimetidine + R1 (T3)Cocktail (R1)
Furosemide202.17 ± 1.04200.61 ± 1.05
Metformin2023.33 ± 1.061540.21 ± 1.07
Rosuvastatin148.32 ± 1.13139.21 ± 1.13
Statistical analysis
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 100.78 · 90% CI 93.59 to 108.51Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 131.37 · 90% CI 120.37 to 143.37Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Cimetidine + R1 (T3) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 106.55 · 90% CI 96.87 to 117.19Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.
SecondaryArea 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.

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.
Reported as:
Geometric mean · Nanomole*hour/litre (nmol*h/L)
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1)
Nanomole*hour/litre (nmol*h/L)Probenecid + R1 (T4)Cocktail (R1)
Furosemide489.28 ± 1.07188.11 ± 1.07
Metformin1346.62 ± 1.081330.47 ± 1.07
Rosuvastatin244.94 ± 1.10113.78 ± 1.10
Statistical analysis
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 260.11 · 90% CI 237.96 to 284.32Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 101.21 · 90% CI 95.15 to 107.66Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.
  • Probenecid + R1 (T4) vs Cocktail (R1) · ANOVA · Adjusted gmean ratio: 215.28 · 90% CI 197.53 to 234.63Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cocktail (R1)0/42 (0%)0/42 (0%)5/42 (11.9%)
Verapamil + R1 (T1)0/12 (0%)0/12 (0%)1/12 (8.3%)
Rifampin + R1 (T2)0/12 (0%)0/12 (0%)2/12 (16.7%)
Metformin (R2)0/16 (0%)0/16 (0%)7/16 (43.8%)
Cimetidine + R1 (T3)0/17 (0%)0/17 (0%)7/17 (41.2%)
Cimetidine + R2 (T5)0/17 (0%)0/17 (0%)7/17 (41.2%)
Furosemide (R3)0/16 (0%)0/16 (0%)4/16 (25%)
Probenecid + R1 (T4)0/16 (0%)0/16 (0%)4/16 (25%)
Probenecid + R3 (T6)0/15 (0%)0/15 (0%)3/15 (20%)
Most frequent other events
Showing 10 of 26
Most frequent other events
EventCocktail (R1)Verapamil + R1 (T1)Rifampin + R1 (T2)Metformin (R2)Cimetidine + R1 (T3)Cimetidine + R2 (T5)Furosemide (R3)Probenecid + R1 (T4)Probenecid + R3 (T6)
HeadacheNervous system disorders2/420/121/124/163/172/172/160/161/15
NauseaGastrointestinal disorders0/420/120/121/161/172/170/161/161/15
VomitingGastrointestinal disorders1/420/121/120/160/171/171/160/160/15
NasopharyngitisInfections and infestations1/421/121/121/160/171/171/161/160/15
Orthostatic intoleranceNervous system disorders0/420/121/120/160/170/170/160/160/15
VertigoEar and labyrinth disorders0/420/120/120/161/171/170/160/161/15
MalaiseGeneral disorders0/420/120/120/160/170/170/160/161/15
Dry eyeEye disorders0/420/120/121/160/170/170/160/160/15
DiarrhoeaGastrointestinal disorders1/420/120/121/161/171/170/160/160/15
Influenza like illnessGeneral disorders0/420/120/121/160/170/170/160/160/15

Baseline characteristics

Treated set (TS): All subjects who were dispended study medication and were documented to have taken at least 1 dose of study medication.

Age, Continuous
Age, Continuous(Years)Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1Total
Part 130.0 ± 6.851.5 ± 1.336.3 ± 10.632.8 ± 10.238.3 ± 13.135.3 ± 11.141.6 ± 10.529.3 ± 7.930.0 ± 8.833.0 ± 13.243.5 ± 8.136.6 ± 10.8
Sex: Female, Male
Sex: Female, Male(Participants)Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1Total
Female000000000000
Male4444445444445
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1Total
Hispanic or Latino000000000000
Not Hispanic or Latino4444445444445
Unknown or Not Reported000000000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)(Verapamil + R1)/ (Rifampin + R1)/ R1(Rifampin + R1)/ R1/ (Verapamil + R1)R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1Total
American Indian or Alaska Native000000000000
Asian000001000001
Native Hawaiian or Other Pacific Islander000000000000
Black or African American000000000000
White4444435444444
More than one race000000000000
Unknown or Not Reported000000000000
07

Study locations

1 site
  • CTC North GmbH & Co. KG, Hamburg
    Hamburg, 20251, Germany
08

References and documents

Study documents

  • Study protocol · Dec 1, 2017
  • Statistical analysis plan · Jun 7, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: 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

09

Registry details

Key details

Study ID
NCT03307252
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Oct 11, 2017
Start date
Oct 25, 2017
Primary completion
May 2, 2018
Completion
May 2, 2018
Results posted
Jul 12, 2019
Last update
Nov 7, 2023

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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