Healthy
Conditions
Brief summary
Main objective is to investigate mutual pharmacokinetic drug-drug interactions of digoxin, furosemide, metformin, and rosuvastatin when given all together as a cocktail
Interventions
DRUGDigoxin
single dose
DRUGFurosemide
single dose
DRUGMetformin
single dose
DRUGRosuvastatin
single dose
DRUGMetformin hydrochloride
10 mg metformin hydrochloride as single dose (all 4 drugs given together as a cocktail at the same time point)
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
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 and local legislation
Exclusion criteria
* Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator * Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * Any evidence of a concomitant disease judged as clinically relevant by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair) * Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders * History of relevant orthostatic hypotension, fainting spells, or blackouts * Chronic or relevant acute infections * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients, sulphonamides, or cardiac glycosides) * Use of drugs within 30 days prior to administration of trial medication that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation (corrected Q-T interval) * Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug * Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) * Inability to refrain from smoking on specified trial days * Alcohol abuse (consumption of more than 30 g per day) * Drug abuse or positive drug screening * Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial * Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial * Inability to comply with dietary regimen of trial site * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration of Rosuvastatin (Cmax) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration | This outcome measure presents the maximum measured concentration of rosuvastatin in plasma (Cmax). Standard error presented is actually geometric standard error. |
| Maximum Concentration of Furosemide (Cmax) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00 and 24:00 after drug administration | This outcome measure presents the maximum measured concentration of furosemide in plasma (Cmax). Standard error presented is actually geometric standard error. |
| Area Under the Curve of Metformin From 0 to Last Quantifiable Data Point (AUC 0-tz) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00 and 48:00 after drug administration | Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error. |
| Maximum Concentration of Metformin (Cmax) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00 and 48:00 after drug administration | This outcome measure presents the maximum measured concentration of metformin in plasma (Cmax). Standard error presented is actually geometric standard error. |
| Area Under the Curve of Rosuvastatin From 0 to Last Quantifiable Data Point (AUC 0-tz) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration | Area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error. |
| Area Under the Curve of Digoxin From 0 to Last Quantifiable Data Point (AUC 0-tz) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration | Area under the concentration-time curve of digoxin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error. CI - confidence interval, gMean - geometric mean. |
| Maximum Concentration of Digoxin (Cmax) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration | This outcome measure presents the maximum measured concentration of digoxin in plasma (Cmax). Standard error presented is actually geometric standard error. |
| Area Under the Curve of Furosemide From 0 to Last Quantifiable Data Point (AUC 0-tz) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00 and 24:00 after drug administration | Area under the concentration-time curve of furosemide in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve of Furosemide From 0 Extrapolated to Infinity (AUC 0-∞) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00 and 24:00 after drug administration | Area under the concentration-time curve of furosemide in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error. |
| Area Under the Curve of Metformin From 0 Extrapolated to Infinity (AUC 0-∞) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00 and 48:00 after drug administration | Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error. |
| Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC 0-∞) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration | Area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error. |
| Area Under the Curve of Digoxin From 0 Extrapolated to Infinity (AUC 0-∞) | Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration | Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error. |
Countries
Germany
Participant flow
Pre-assignment details
This is an open-label, randomised, single-dose, five-way, ten-sequence crossover study. Four drugs (Digoxin (R1), Furosemide, (R2), Metformin hydrochloride (R3), Rosuvastatin (R4)) were given as monotherapy and one as a combination of all four drugs together as test cocktail (T) in pre-defined sequences.
Participants by arm
| Arm | Count |
|---|---|
| ABECD (R1->R2->T->R3->R4) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (reference 1 or R1). Second, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Third, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fourth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fifth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4).
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| AEBDC (R1->T->R2->R4->R3) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (reference 1 or R1). Second, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Third, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fourth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fifth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3).
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| BACED (R2->R1->R3->T->R4) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (reference 2 or R2). Second, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Third, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fourth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fifth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4).
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| BCADE (R2->R3->R1->R4->T) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Second, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Third, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fourth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fifth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin.
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| CBDAE (R3->R2->R4->R1->T) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Second, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Third, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fourth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fifth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin.
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| CDBEA (R3->R4->R2->T->R1) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Second, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Third, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fourth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fifth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1).
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| DCEBA (R4->R3->T->R2->R1) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Second, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Third, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fourth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fifth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1).
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| DECAB (R4->T->R3->R1->R2) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Second, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Third, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fourth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fifth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2).
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| EADBC (T->R1->R4->R2->R3) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Second, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Third, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fourth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fifth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3).
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| EDACB (T->R4->R1->R3->R2) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Second, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Third, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fourth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fifth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2).
All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours. | 3 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | ABECD (R1->R2->T->R3->R4) | AEBDC (R1->T->R2->R4->R3) | BACED (R2->R1->R3->T->R4) | BCADE (R2->R3->R1->R4->T) | CBDAE (R3->R2->R4->R1->T) | CDBEA (R3->R4->R2->T->R1) | DCEBA (R4->R3->T->R2->R1) | DECAB (R4->T->R3->R1->R2) | EADBC (T->R1->R4->R2->R3) | EDACB (T->R4->R1->R3->R2) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35.5 Years STANDARD_DEVIATION 9.4 | 26.7 Years STANDARD_DEVIATION 2.5 | 28.7 Years STANDARD_DEVIATION 8.1 | 41.3 Years STANDARD_DEVIATION 15.8 | 42.0 Years STANDARD_DEVIATION 5.3 | 32.3 Years STANDARD_DEVIATION 9 | 45.7 Years STANDARD_DEVIATION 7.2 | 30.3 Years STANDARD_DEVIATION 6.4 | 33.0 Years STANDARD_DEVIATION 9.6 | 40.3 Years STANDARD_DEVIATION 7.5 | 34.3 Years STANDARD_DEVIATION 7.2 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 30 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 28 | 0 / 30 | 1 / 29 | 1 / 29 | 3 / 28 |
| serious Total, serious adverse events | 1 / 28 | 0 / 30 | 0 / 29 | 0 / 29 | 0 / 28 |
Outcome results
Primary
Area Under the Curve of Digoxin From 0 to Last Quantifiable Data Point (AUC 0-tz)
Area under the concentration-time curve of digoxin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error. CI - confidence interval, gMean - geometric mean.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration
Population: The Pharmacokinetic (PK) analysis set (PKS) included all randomized subjects who were documented to have taken at least 1 dose of study drug and who have provided at least 1 primary or secondary PK endpoint that was not excluded from analysis due to non-evaluability or protocol violation relevant for the evaluation of the pharmacokinetics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Area Under the Curve of Digoxin From 0 to Last Quantifiable Data Point (AUC 0-tz) | 11.549 nanomole hour per liter (nmol·h/L) | Standard Error 1.053 |
| Digoxin (R1) | Area Under the Curve of Digoxin From 0 to Last Quantifiable Data Point (AUC 0-tz) | 11.981 nanomole hour per liter (nmol·h/L) | Standard Error 1.053 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the first primary outcome measure of treatment R1.90% CI: [88.22, 105.33]ANOVA
Primary
Area Under the Curve of Furosemide From 0 to Last Quantifiable Data Point (AUC 0-tz)
Area under the concentration-time curve of furosemide in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00 and 24:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Area Under the Curve of Furosemide From 0 to Last Quantifiable Data Point (AUC 0-tz) | 163.614 nmol·h/L | Standard Error 1.039 |
| Digoxin (R1) | Area Under the Curve of Furosemide From 0 to Last Quantifiable Data Point (AUC 0-tz) | 159.434 nmol·h/L | Standard Error 1.038 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the first primary outcome measure of treatment R2.90% CI: [93.82, 112.25]ANOVA
Primary
Area Under the Curve of Metformin From 0 to Last Quantifiable Data Point (AUC 0-tz)
Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00 and 48:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Area Under the Curve of Metformin From 0 to Last Quantifiable Data Point (AUC 0-tz) | 1283.797 nmol·h/L | Standard Error 1.034 |
| Digoxin (R1) | Area Under the Curve of Metformin From 0 to Last Quantifiable Data Point (AUC 0-tz) | 1316.790 nmol·h/L | Standard Error 1.033 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the first primary outcome measure of treatment R3.90% CI: [93.54, 101.61]ANOVA
Primary
Area Under the Curve of Rosuvastatin From 0 to Last Quantifiable Data Point (AUC 0-tz)
Area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Area Under the Curve of Rosuvastatin From 0 to Last Quantifiable Data Point (AUC 0-tz) | 81.925 nmol·h/L | Standard Error 1.07 |
| Digoxin (R1) | Area Under the Curve of Rosuvastatin From 0 to Last Quantifiable Data Point (AUC 0-tz) | 78.016 nmol·h/L | Standard Error 1.069 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the first primary outcome measure of treatment R4.90% CI: [96.39, 114.4]ANOVA
Primary
Maximum Concentration of Digoxin (Cmax)
This outcome measure presents the maximum measured concentration of digoxin in plasma (Cmax). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Maximum Concentration of Digoxin (Cmax) | 1.262 nanomole per liter (nmol/L) | Standard Error 1.047 |
| Digoxin (R1) | Maximum Concentration of Digoxin (Cmax) | 1.355 nanomole per liter (nmol/L) | Standard Error 1.047 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the second primary outcome measure of treatment R1.90% CI: [83.49, 103.97]ANOVA
Primary
Maximum Concentration of Furosemide (Cmax)
This outcome measure presents the maximum measured concentration of furosemide in plasma (Cmax). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00 and 24:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Maximum Concentration of Furosemide (Cmax) | 86.275 nmol/L | Standard Error 1.046 |
| Digoxin (R1) | Maximum Concentration of Furosemide (Cmax) | 82.990 nmol/L | Standard Error 1.044 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the second primary outcome measure of treatment R2.90% CI: [93.6, 115.46]ANOVA
Primary
Maximum Concentration of Metformin (Cmax)
This outcome measure presents the maximum measured concentration of metformin in plasma (Cmax). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00 and 48:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Maximum Concentration of Metformin (Cmax) | 225.156 nmol/L | Standard Error 1.045 |
| Digoxin (R1) | Maximum Concentration of Metformin (Cmax) | 229.171 nmol/L | Standard Error 1.044 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the second primary outcome measure of treatment R3.90% CI: [91.85, 105.09]ANOVA
Primary
Maximum Concentration of Rosuvastatin (Cmax)
This outcome measure presents the maximum measured concentration of rosuvastatin in plasma (Cmax). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Maximum Concentration of Rosuvastatin (Cmax) | 8.135 nmol/L | Standard Error 1.074 |
| Digoxin (R1) | Maximum Concentration of Rosuvastatin (Cmax) | 7.801 nmol/L | Standard Error 1.073 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the second primary outcome measure of treatment R4.90% CI: [94.95, 114.53]ANOVA
Secondary
Area Under the Curve of Digoxin From 0 Extrapolated to Infinity (AUC 0-∞)
Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Area Under the Curve of Digoxin From 0 Extrapolated to Infinity (AUC 0-∞) | 17.668 nmol·h/L | Standard Error 1.039 |
| Digoxin (R1) | Area Under the Curve of Digoxin From 0 Extrapolated to Infinity (AUC 0-∞) | 18.303 nmol·h/L | Standard Error 1.039 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the secondary outcome measure of treatment R1.90% CI: [92.08, 101.2]ANOVA
Secondary
Area Under the Curve of Furosemide From 0 Extrapolated to Infinity (AUC 0-∞)
Area under the concentration-time curve of furosemide in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00 and 24:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Area Under the Curve of Furosemide From 0 Extrapolated to Infinity (AUC 0-∞) | 156.382 nmol·h/L | Standard Error 1.049 |
| Digoxin (R1) | Area Under the Curve of Furosemide From 0 Extrapolated to Infinity (AUC 0-∞) | 160.551 nmol·h/L | Standard Error 1.052 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the secondary outcome measure of treatment R2.90% CI: [90.87, 104.41]ANOVA
Secondary
Area Under the Curve of Metformin From 0 Extrapolated to Infinity (AUC 0-∞)
Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00 and 48:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Area Under the Curve of Metformin From 0 Extrapolated to Infinity (AUC 0-∞) | 1290.928 nmol·h/L | Standard Error 1.033 |
| Digoxin (R1) | Area Under the Curve of Metformin From 0 Extrapolated to Infinity (AUC 0-∞) | 1324.078 nmol·h/L | Standard Error 1.033 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the secondary outcome measure of treatment R3.90% CI: [93.58, 101.58]ANOVA
Secondary
Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC 0-∞)
Area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error.
Time frame: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Test Cocktail (T) | Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC 0-∞) | 97.385 nmol·h/L | Standard Error 1.072 |
| Digoxin (R1) | Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC 0-∞) | 90.479 nmol·h/L | Standard Error 1.069 |
Comparison: This statistical analysis assess the effect of the other cocktail compounds in treatment T on the secondary outcome measure of treatment R4.90% CI: [97.04, 119.39]ANOVA