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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-001549-29 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Reference 1 | Experimental |
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| Treatment Reference 2 | Experimental |
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| Treatment Reference 3 | Experimental |
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| Treatment 1 | Experimental |
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| Treatment 2 | Experimental |
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| Treatment 3 | Experimental |
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| Treatment 4 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Digoxin | Drug | Tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1) | AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. Geometric mean (gMean) presented here is an adjusted gMean and standard error (SE) presented is a geometric SE (gSE). | Samples were taken within 0:20 hour:minutes (hh:mm) prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1) | AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE. | Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1) | AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE. | Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CTC North GmbH & Co. KG, Hamburg | Hamburg | 20251 | Germany |
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
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All participants were screened for eligibility to participate in the trial. Participants were not to be randomised to trial treatment if any of the in- or exclusion criteria were violated at screening.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1) | In trial part 1 participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 milliliter (mL) of water in period 1. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to R1 which is administered with 280 mL of water in period 2. In period 3 participants were administered a single dose of 600 mg Rifampin film-coated tablet with 280 mL of water together with R1. Treatment periods were separated by a wash-out period of 13 days. |
| FG001 | (Verapamil + R1)/ (Rifampin + R1)/ R1 | In trial part 1 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to R1 which is administered with 280 mL of water in period 1. Followed by a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 2. In period 3 participants were administered a single dose of R1 with 280 milliliter (mL) of water. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Treatment periods were separated by a wash-out period of 13 days. |
| FG002 | (Rifampin + R1)/ R1/ (Verapamil + R1) | In trial part 1 participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 1. Followed by a single dose of R1 with 280 mL of water in period 2. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. In period 3 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to the R1 which is administered with 280 mL of water. Treatment periods were separated by a wash-out period of 13 days. |
| FG003 | R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin) | In trial part 2 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 2. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 3. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to therapeutic dose of 500mg of Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| FG004 | Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1) | In trial part 2 participants were administered single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 2. Followed by a single dose of R1 with 280 mL of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| FG005 | (Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin | In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 2. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 3. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| FG006 | (Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1 | In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 2. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| FG007 | R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide) | In trial part 3 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 2. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 3. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| FG008 | Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1) | In trial part 3 participants were administered single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 1. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 2. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| FG009 | (Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide | In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 2. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 3. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| FG010 | (Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1 | In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 1. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 2. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 4. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
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| Part 1, Period 1 |
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| Part 1, Washout Period 1 (13 Days) |
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| Part 1, Period 2 |
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| Part 1, Washout Period 2 (13 Days) |
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| Part 1, Period 3 |
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| Part 2, Period 1 |
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| Part 2, Washout Period 1 (7 Days) |
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| Part 2, Period 2 |
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| Part 2, Washout Period 2 (7 Days) |
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| Part 2, Period 3 |
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| Part 2, Washout Period 3 (7 Days) |
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| Part 2, Period 4 |
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| Part 3, Period 1 |
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| Part 3, Washout Period 1 (7 Days) |
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| Part 3, Period 2 |
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| Part 3, Washout Period 2 (7 Days) |
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| Part 3, Washout Period 3 (7 Days) |
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| Part 3, Period 4 |
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Treated set (TS): All subjects who were dispended study medication and were documented to have taken at least 1 dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1) | In trial part 1 participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 milliliter (mL) of water in period 1. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to R1 which is administered with 280 mL of water in period 2. In period 3 participants were administered a single dose of 600 mg Rifampin film-coated tablet with 280 mL of water together with R1. Treatment periods were separated by a wash-out period of 13 days. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Pharmacokinetic (PK) parameter analysis set (PKS): All subjects in the TS providing at least 1 primary or secondary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. | Posted | Geometric Mean | Standard Error | Nanomole*hour/litre (nmol*h/L) | 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. |
|
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.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cocktail (R1) | Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Centre | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 1, 2017 | Apr 29, 2019 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 7, 2018 | Apr 29, 2019 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D004077 | Digoxin |
| D005665 | Furosemide |
| D008687 | Metformin |
| D000068718 | Rosuvastatin Calcium |
| D014700 | Verapamil |
| D012293 | Rifampin |
| D002927 | Cimetidine |
| D011339 | Probenecid |
| ID | Term |
|---|---|
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
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| Treatment 5 | Experimental |
|
| Treatment 6 | Experimental |
|
| Furosemide | Drug | Oral solution |
|
| Metformin | Drug | Oral solution |
|
| Rosuvastatin | Drug | Film-coated tablet |
|
| Verapamil | Drug | Film-coated tablet |
|
| Rifampin | Drug | Film-coated tablet |
|
| Cimetidine | Drug | Tablet |
|
| Probenecid | Drug | Tablet |
|
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1) | AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE. | Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1) | Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE. | Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1) | Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE. | Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1) | Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE. | Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1) | Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE. | Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1) | AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE. | Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1) | AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE. | Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration. |
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1) | AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE. | 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. |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG001 | (Verapamil + R1)/ (Rifampin + R1)/ R1 | In trial part 1 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to R1 which is administered with 280 mL of water in period 1. Followed by a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 2. In period 3 participants were administered a single dose of R1 with 280 milliliter (mL) of water. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Treatment periods were separated by a wash-out period of 13 days. |
| BG002 | (Rifampin + R1)/ R1/ (Verapamil + R1) | In trial part 1 participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 1. Followed by a single dose of R1 with 280 mL of water in period 2. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. In period 3 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to the R1 which is administered with 280 mL of water. Treatment periods were separated by a wash-out period of 13 days. |
| BG003 | R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin) | In trial part 2 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 2. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 3. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to therapeutic dose of 500mg of Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| BG004 | Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1) | In trial part 2 participants were administered single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 2. Followed by a single dose of R1 with 280 mL of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| BG005 | (Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin | In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 2. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 3. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| BG006 | (Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1 | In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 2. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| BG007 | R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide) | In trial part 3 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 2. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 3. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| BG008 | Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1) | In trial part 3 participants were administered single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 1. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 2. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| BG009 | (Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide | In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 2. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 3. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| BG010 | (Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1 | In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 1. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 2. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 4. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days. |
| BG011 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 | Verapamil + R1 (T1) | Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1. |
| OG001 | Cocktail (R1) | Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3. |
|
|
|
| Primary | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole*hour/litre (nmol*h/L) | 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. |
|
|
|
|
| Primary | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole*hour/litre (nmol*h/L) | 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. |
|
|
|
|
| Primary | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole*hour/litre (nmol*h/L) | 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. |
|
|
|
|
| Primary | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole/ litre (nmol/ L) | 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. |
|
|
|
|
| Primary | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole/ litre (nmol/ L) | 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. |
|
|
|
|
| Primary | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole/ litre (nmol/ L) | 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. |
|
|
|
|
| Primary | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole/ litre (nmol/ L) | 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 | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole*hour/litre (nmol*h/L) | 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 | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole*hour/litre (nmol*h/L) | 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 | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole*hour/litre (nmol*h/L) | 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 | 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. | PKS | Posted | Geometric Mean | Standard Error | Nanomole*hour/litre (nmol*h/L) | 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. |
|
|
|
|
| 0 |
| 42 |
| 0 |
| 42 |
| 5 |
| 42 |
| EG001 | Verapamil + R1 (T1) | Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1. | 0 | 12 | 0 | 12 | 1 | 12 |
| EG002 | Rifampin + R1 (T2) | Participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in trial part 1. | 0 | 12 | 0 | 12 | 2 | 12 |
| EG003 | Metformin (R2) | Participants were administered a single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in trial part 2. | 0 | 16 | 0 | 16 | 7 | 16 |
| EG004 | Cimetidine + R1 (T3) | Participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2). All doses of Cimetidine administered with 240 mL water and dose of R1 which is administered with 280 mL of water in trial part 2. | 0 | 17 | 0 | 17 | 7 | 17 |
| EG005 | Cimetidine + R2 (T5) | Participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after therapeutic dose of 500 mg Metformin (Day 2) in trial part 2. | 0 | 17 | 0 | 17 | 7 | 17 |
| EG006 | Furosemide (R3) | Participants were administered orally a single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in trial part 3. | 0 | 16 | 0 | 16 | 4 | 16 |
| EG007 | Probenecid + R1 (T4) | Participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) orally 13 h prior and again 1 h prior to the administration of R1 on day 1. All doses of Cimetidine administered with 240 mL water and dose of R1 which is administered with 280 mL of water in trial part 3. | 0 | 16 | 0 | 16 | 4 | 16 |
| EG008 | Probenecid + R3 (T6) | Participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in trial part 3. | 0 | 15 | 0 | 15 | 3 | 15 |
| Vertigo | Ear and labyrinth disorders | MedDRA 21.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 21.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 21.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 21.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 21.0 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 21.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
|
| Orthostatic intolerance | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
|
| Conversion disorder | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D013424 | Sulfanilamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D007093 | Imidazoles |
| D001393 | Azoles |
| Metformin |
|
| Rosuvastatin |
|
| ANOVA | Adjusted gMean ratio | 119.78 | Standard Error of the Mean | 12.1 | 2-Sided | 90 | 110.03 | 130.39 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1. | Other | Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 108.55 | Standard Error of the Mean | 10.7 | 2-Sided | 90 | 100.68 | 117.03 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 348.06 | Standard Error of the Mean | 21.5 | 2-Sided | 90 | 299.64 | 404.31 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Metformin |
|
| Rosuvastatin |
|
| ANOVA | Adjusted gMean ratio | 101.21 | Standard Error of the Mean | 9.2 | 2-Sided | 90 | 94.59 | 108.30 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1. | Other | Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 130.94 | Standard Error of the Mean | 13.6 | 2-Sided | 90 | 119.82 | 143.10 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 107.42 | Standard Error of the Mean | 12.9 | 2-Sided | 90 | 97.57 | 118.27 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Metformin |
|
| Rosuvastatin |
|
| ANOVA | Adjusted gMean ratio | 271.63 | Standard Error of the Mean | 15.9 | 2-Sided | 90 | 246.74 | 299.03 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 100.80 | Standard Error of the Mean | 9.6 | 2-Sided | 90 | 94.62 | 107.39 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 223.24 | Standard Error of the Mean | 13.9 | 2-Sided | 90 | 203.79 | 244.55 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Metformin |
|
| Rosuvastatin |
|
| ANOVA | Adjusted gMean ratio | 95.18 | Standard Error of the Mean | 19.6 | 2-Sided | 90 | 83.03 | 109.11 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1. | Other | Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 80.19 | Standard Error of the Mean | 13.4 | 2-Sided | 90 | 73.01 | 88.08 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 115.39 | Standard Error of the Mean | 30.1 | 2-Sided | 90 | 93.80 | 141.94 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Metformin |
|
| Rosuvastatin |
|
| ANOVA | Adjusted gMean ratio | 135.07 | Standard Error of the Mean | 19.6 | 2-Sided | 90 | 117.83 | 154.84 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1. | Other | Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 112.31 | Standard Error of the Mean | 13.4 | 2-Sided | 90 | 102.26 | 123.35 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 1125.10 | Standard Error of the Mean | 30.1 | 2-Sided | 90 | 914.63 | 1384.00 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Metformin |
|
| Rosuvastatin |
|
| ANOVA | Adjusted gMean ratio | 104.78 | Standard Error of the Mean | 21.0 | 2-Sided | 90 | 89.97 | 122.03 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1. | Other | Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 122.65 | Standard Error of the Mean | 20.1 | 2-Sided | 90 | 107.68 | 139.69 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 116.88 | Standard Error of the Mean | 14.4 | 2-Sided | 90 | 105.07 | 130.03 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Metformin |
|
| Rosuvastatin |
|
| ANOVA | Adjusted gMean ratio | 122.94 | Standard Error of the Mean | 18.0 | 2-Sided | 90 | 110.25 | 137.09 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 101.35 | Standard Error of the Mean | 12.0 | 2-Sided | 90 | 93.65 | 109.70 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 428.23 | Standard Error of the Mean | 26.8 | 2-Sided | 90 | 359.78 | 509.70 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Rosuvastatin |
|
| ANOVA | Adjusted gMean Ratio | 83.99 | Standard Error of the Mean | 10.0 | 2-Sided | 90 | 78.32 | 90.08 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 124.06 | Standard Error of the Mean | 23.9 | 2-Sided | 90 | 105.11 | 146.43 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Rosuvastatin |
|
| ANOVA | Adjusted gMean Ratio | 108.56 | Standard Error of the Mean | 10.0 | 2-Sided | 90 | 101.22 | 116.43 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 340.67 | Standard Error of the Mean | 23.9 | 2-Sided | 90 | 288.63 | 402.10 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Rosuvastatin |
|
| ANOVA | Adjusted gMean Ratio | 131.37 | Standard Error of the Mean | 13.4 | 2-Sided | 90 | 120.37 | 143.37 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 106.55 | Standard Error of the Mean | 12.8 | 2-Sided | 90 | 96.87 | 117.19 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Rosuvastatin |
|
| ANOVA | Adjusted gMean Ratio | 101.21 | Standard Error of the Mean | 9.4 | 2-Sided | 90 | 95.15 | 107.66 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| ANOVA | Adjusted gMean Ratio | 215.28 | Standard Error of the Mean | 13.1 | 2-Sided | 90 | 197.53 | 234.63 | Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1. | Other | Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |