Relative Bioavailability of 2 Fixed Dose Combinations of Empagliflozin/Linagliptin/Metformin Extended Release Compared With Single Tablets
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT02821910
Collaborator
Eli Lilly and Company (Industry)
50
1
3
3.4
14.8
Study Details
Study Description
Brief Summary
The purpose of this trial is to demonstrate the relative bioavailability of 2 newly developed fixed dose combinations (FDC) tablets containing empagliflozin, linagliptin & metformin extended release (XR) and the single tablets of empagliflozin, linagliptin and metformin XR administered simultaneously.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
50 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Relative Bioavailability of Two FDC Tablet Strengths of Empagliflozin/Linagliptin/Metformin Extended Release Compared to the Free Combination of Empagliflozin, Linagliptin and Metformin Extended Release Following Oral Administration in Healthy Male and Female Subjects (an Open-label, Randomised, Single-dose, Two-period, Two-sequence Crossover Study)
Actual Study Start Date
:
Jul 20, 2016
Actual Primary Completion Date
:
Oct 1, 2016
Actual Study Completion Date
:
Oct 31, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: High dose, fed 1 fixed dose combination (FDC) tablet vs. 4 single tablets under fed conditions |
Drug: High dose FDC Empagliflozin/Linagliptin/Metformin XR, fed
High dose Empagliflozin/Linagliptin/Metformin extended release (XR) fixed dose combination (FDC) tablet
Drug: 1 tab Empagliflozin +1 tab Linagliptin +2 tabs Metformin XR
1x Empagliflozin + 1x Linagliptin + 2x Metformin extended release (XR) tablets
|
| Experimental: High dose, fasted 1 fixed dose combination (FDC) tablet vs. 4 single tablets under fasted conditions |
Drug: High dose FDC Empagliflozin/Linagliptin/Metformin XR, fasted
High dose Empagliflozin/Linagliptin/Metformin extended release (XR) fixed dose combination (FDC) tablet
Drug: 1 tab Empagliflozin +1 tab Linagliptin +2 tabs Metformin XR
1x Empagliflozin + 1x Linagliptin + 2x Metformin extended release (XR) tablets
|
| Experimental: Low dose, fed 1 fixed dose combination (FDC) tablet vs. 4 single tablets under fed conditions |
Drug: Low dose FDC Empagliflozin/Linagliptin/Metformin XR, fed
Low dose Empagliflozin/Linagliptin/Metformin extended release (XR) fixed dose combination (FDC) tablet
Drug: 1 tab Empagliflozin +1 tab Linagliptin +2 tabs Metformin XR
1x Empagliflozin + 1x Linagliptin + 2x Metformin extended release (XR) tablets
|
Outcome Measures
Primary Outcome Measures
- Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Concentration (AUC0-tz) [1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration]
Area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz) is presented. Plasma concentrations and/or parameters of a subject were considered as non-evaluable, if for example The subject experienced emesis that occurred at or before 2 times median tmax of the respective treatment (median tmax was to be determined excluding the subject's experiencing emesis) A pre-dose concentration was >5% of the Cmax value measured in that subject Missing samples or concentration data at important phases of PK disposition curve
- Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Concentration (AUC0-tz) [1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration]
Area under the concentration-time curve of Metformin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz) is presented
- Maximum Measured Concentration of Empagliflozin in Plasma (Cmax) [1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration]
Maximum measured concentration of Empagliflozin in plasma (Cmax) is presented
- Maximum Measured Concentration of Metformin in Plasma (Cmax) [1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration]
Maximum measured concentration of Metformin in plasma (Cmax) is presented
- Maximum Measured Concentration of Linagliptin in Plasma (Cmax) [1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration]
Maximum measured concentration of Linagliptin in plasma (Cmax) is presented
- Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) [1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration]
Area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 to 72 hours (AUC0-72) is presented
Secondary Outcome Measures
- Area Under the Concentration-time Curve of the Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) [1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration]
Area under the concentration-time curve of the Empagliflozin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented
- Area Under the Concentration-time Curve of the Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) [1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration]
Area under the concentration-time curve of the Metformin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented
- Area Under the Concentration-time Curve of the Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) [1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration]
Area under the concentration-time curve of the Linagliptin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion criteria:
-
Healthy male or female subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram, and clinical laboratory tests
-
Age of 18 to 55 years (incl.)
-
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 GCP and local legislation
-
Male subjects, or female subjects who meet any of the following criteria starting from at least 30 days before the first administration of trial medication and until 30 days after trial completion:
Use of adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device Sexually abstinent A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment) Surgically sterilised (including hysterectomy) Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle-stimulating hormone above 40 U/L and estradiol below 30 ng/L is confirmatory)
Exclusion criteria:
-
Any finding in the medical examination (including blood pressure, pulse rate or electrocardiogram) 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 45 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
-
Further exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Humanpharmakologisches Zentrum Biberach | Biberach | Germany | 88397 |
Sponsors and Collaborators
- Boehringer Ingelheim
- Eli Lilly and Company
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02821910
Other Study ID Numbers:
- 1361.1
- 2015-005082-23
First Posted:
Jul 4, 2016
Last Update Posted:
Mar 5, 2020
Last Verified:
Feb 1, 2020
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | The subjects were randomly allocated to the 2 treatment sequences (test (T) - reference (R) or R-T) in 3 separate trial parts. There was a wash-out period of at least 35 days between the treatments.Treatments were administered as single doses in the fed state in Parts 1 and 3, and in the fasted state in Part 2. |
| Arm/Group Title | FDC 25 Fed (T1)/ E25+L5+M1000 Fed (R1) (Part 1) | E25+L5+M1000 Fed (R1)/ FDC 25 Fed (T1) (Part 1) | FDC 25 Fast (T2)/ E25+L5+M1000 Fast (R2) (Part 2) | E25+L5+M1000 Fast (R2)/ FDC 25 Fast (T2) (Part 2) | FDC 10 Fed (T3)/ E10+L5+M1000 Fed (R3) (Part 3) | E10+L5+M1000 Fed (R3)/ FDC 10 Fed (T3) (Part 3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 milligram (mg) empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 millilitre (mL) of water after a high-fat, high-calorie breakfast followed by a wash-out period of at least 35 days and then orally administered free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast followed by a wash-out period of at least 35 days and then orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h followed by a wash-out period of at least 35 days and then orally administered free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after an overnight fast of at least 10 h followed by a wash-out period of at least 35 days and then orally administered 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast followed by a wash-out period of at least 35 days and then orally administered free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast followed by a wash-out period of at least 35 days and then orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast |
| Period Title: Overall Study | ||||||
| STARTED | 7 | 8 | 10 | 10 | 7 | 8 |
| COMPLETED | 6 | 8 | 8 | 10 | 7 | 7 |
| NOT COMPLETED | 1 | 0 | 2 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | FDC 25 Fed (T1)/ E25+L5+M1000 Fed (R1) (Part 1) | E25+L5+M1000 Fed (R1)/ FDC 25 Fed (T1) (Part 1) | FDC 25 Fast (T2)/ E25+L5+M1000 Fast (R2) (Part 2) | E25+L5+M1000 Fast (R2)/ FDC 25 Fast (T2) (Part 2) | FDC 10 Fed (T3)/ E10+L5+M1000 Fed (R3) (Part 3) | E10+L5+M1000 Fed (R3)/ FDC 10 Fed (T3) (Part 3) | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 milligram (mg) empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 millilitre (mL) of water after a high-fat, high-calorie breakfast followed by a wash-out period of at least 35 days and then orally administered free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast followed by a wash-out period of at least 35 days and then orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h followed by a wash-out period of at least 35 days and then orally administered free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after an overnight fast of at least 10 h followed by a wash-out period of at least 35 days and then orally administered 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast followed by a wash-out period of at least 35 days and then orally administered free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast followed by a wash-out period of at least 35 days and then orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Total of all reporting groups |
| Overall Participants | 7 | 8 | 10 | 10 | 7 | 8 | 50 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
36.7
(8.9)
|
37.1
(11.9)
|
36.2
(12.3)
|
34.1
(10.0)
|
37.3
(11.9)
|
35.3
(9.4)
|
36.0
(10.4)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
3
42.9%
|
4
50%
|
7
70%
|
2
20%
|
4
57.1%
|
1
12.5%
|
21
42%
|
| Male |
4
57.1%
|
4
50%
|
3
30%
|
8
80%
|
3
42.9%
|
7
87.5%
|
29
58%
|
Outcome Measures
| Title | Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Concentration (AUC0-tz) |
|---|---|
| Description | Area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz) is presented. Plasma concentrations and/or parameters of a subject were considered as non-evaluable, if for example The subject experienced emesis that occurred at or before 2 times median tmax of the respective treatment (median tmax was to be determined excluding the subject's experiencing emesis) A pre-dose concentration was >5% of the Cmax value measured in that subject Missing samples or concentration data at important phases of PK disposition curve |
| Time Frame | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) parameter analysis set (PKS): This subject set included all subjects in the TS who provided at least 1 primary or secondary PK parameter that was not excluded according to the criterion's for non-evaluable above. |
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast |
| Measure Participants | 15 | 14 | 20 | 18 | 14 | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [nanomoles (nmol)*hours (h)/litres (L)] |
5990
(25.6)
|
6120
(22.8)
|
6430
(20.2)
|
6250
(18.7)
|
2080
(15.4)
|
2130
(15.5)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fed (T1), E25+L5+M1000 Fed (R1) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 96.70 | |
| Confidence Interval |
(2-Sided) 90% 92.89 to 100.66 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 5.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T1 divided by R1. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fast (T2), E25+L5+M1000 Fast (R2) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 100.80 | |
| Confidence Interval |
(2-Sided) 90% 97.99 to 103.70 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 4.8 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T2 divided by R2. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FDC 10 Fed (T3), E10+L5+M1000 Fed (R3) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 99.83 | |
| Confidence Interval |
(2-Sided) 90% 95.96 to 103.85 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 5.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T3 divided by R3. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
| Title | Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Concentration (AUC0-tz) |
|---|---|
| Description | Area under the concentration-time curve of Metformin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz) is presented |
| Time Frame | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast |
| Measure Participants | 15 | 14 | 20 | 18 | 14 | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [nanograms (ng)*h/ milliliter (mL)] |
13900
(29.6)
|
13900
(30.9)
|
7920
(31.3)
|
8260
(33.4)
|
12000
(26.0)
|
12200
(25.9)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fed (T1), E25+L5+M1000 Fed (R1) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 96.82 | |
| Confidence Interval |
(2-Sided) 90% 90.65 to 103.42 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 9.7 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T1 divided by R1. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fast (T2), E25+L5+M1000 Fast (R2) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 95.67 | |
| Confidence Interval |
(2-Sided) 90% 87.44 to 104.68 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 15.5 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T2 divided by R2. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FDC 10 Fed (T3), E10+L5+M1000 Fed (R3) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 98.47 | |
| Confidence Interval |
(2-Sided) 90% 92.12 to 105.25 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 9.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T3 divided by R3. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
| Title | Maximum Measured Concentration of Empagliflozin in Plasma (Cmax) |
|---|---|
| Description | Maximum measured concentration of Empagliflozin in plasma (Cmax) is presented |
| Time Frame | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast |
| Measure Participants | 15 | 14 | 20 | 18 | 14 | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
594
(17.7)
|
630
(20.4)
|
872
(24.5)
|
817
(31.5)
|
232
(20.5)
|
235
(18.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fed (T1), E25+L5+M1000 Fed (R1) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 94.94 | |
| Confidence Interval |
(2-Sided) 90% 86.60 to 104.08 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 13.8 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T1 divided by R1. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fast (T2), E25+L5+M1000 Fast (R2) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 106.63 | |
| Confidence Interval |
(2-Sided) 90% 100.65 to 112.96 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 9.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T2 divided by R2. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FDC 10 Fed (T3), E10+L5+M1000 Fed (R3) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 100.41 | |
| Confidence Interval |
(2-Sided) 90% 94.54 to 106.64 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 8.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T3 divided by R3. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
| Title | Maximum Measured Concentration of Metformin in Plasma (Cmax) |
|---|---|
| Description | Maximum measured concentration of Metformin in plasma (Cmax) is presented |
| Time Frame | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast |
| Measure Participants | 15 | 14 | 20 | 18 | 14 | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
1290
(25.0)
|
1300
(21.4)
|
1010
(31.1)
|
1020
(32.8)
|
1170
(33.3)
|
1150
(32.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fed (T1), E25+L5+M1000 Fed (R1) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 97.97 | |
| Confidence Interval |
(2-Sided) 90% 91.46 to 104.94 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 10.2 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T1 divided by R1. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fast (T2), E25+L5+M1000 Fast (R2) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 100.04 | |
| Confidence Interval |
(2-Sided) 90% 90.23 to 110.91 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 17.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T2 divided by R2. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FDC 10 Fed (T3), E10+L5+M1000 Fed (R3) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 101.24 | |
| Confidence Interval |
(2-Sided) 90% 94.58 to 108.38 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 10.1 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T3 divided by R3. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
| Title | Maximum Measured Concentration of Linagliptin in Plasma (Cmax) |
|---|---|
| Description | Maximum measured concentration of Linagliptin in plasma (Cmax) is presented |
| Time Frame | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast |
| Measure Participants | 15 | 14 | 20 | 18 | 14 | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
6.37
(20.6)
|
6.51
(19.4)
|
9.66
(44.5)
|
8.35
(27.2)
|
6.25
(23.1)
|
6.15
(22.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fed (T1), E25+L5+M1000 Fed (R1) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 97.50 | |
| Confidence Interval |
(2-Sided) 90% 89.94 to 105.71 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 12.0 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T1 divided by R1. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fast (T2), E25+L5+M1000 Fast (R2) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 117.31 | |
| Confidence Interval |
(2-Sided) 90% 103.41 to 133.07 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 22.0 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T2 divided by R2. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FDC 10 Fed (T3), E10+L5+M1000 Fed (R3) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 102.74 | |
| Confidence Interval |
(2-Sided) 90% 98.56 to 107.10 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 6.2 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T3 divided by R3. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
| Title | Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) |
|---|---|
| Description | Area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 to 72 hours (AUC0-72) is presented |
| Time Frame | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast |
| Measure Participants | 15 | 14 | 20 | 18 | 14 | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
273
(18.7)
|
282
(17.2)
|
290
(24.7)
|
276
(21.1)
|
258
(25.1)
|
260
(20.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fed (T1), E25+L5+M1000 Fed (R1) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 96.34 | |
| Confidence Interval |
(2-Sided) 90% 92.13 to 100.75 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 6.6 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T1 divided by R1. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fast (T2), E25+L5+M1000 Fast (R2) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 105.07 | |
| Confidence Interval |
(2-Sided) 90% 99.95 to 110.45 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 8.6 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T2 divided by R2. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FDC 10 Fed (T3), E10+L5+M1000 Fed (R3) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 100.31 | |
| Confidence Interval |
(2-Sided) 90% 96.41 to 104.38 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 5.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T3 divided by R3. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
| Title | Area Under the Concentration-time Curve of the Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) |
|---|---|
| Description | Area under the concentration-time curve of the Empagliflozin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented |
| Time Frame | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast |
| Measure Participants | 15 | 14 | 20 | 18 | 14 | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
6060
(25.7)
|
6190
(22.5)
|
6490
(20.0)
|
6300
(18.7)
|
2130
(15.5)
|
2180
(15.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fed (T1), E25+L5+M1000 Fed (R1) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 96.63 | |
| Confidence Interval |
(2-Sided) 90% 92.86 to 100.54 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 5.8 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T1 divided by R1. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fast (T2), E25+L5+M1000 Fast (R2) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 100.87 | |
| Confidence Interval |
(2-Sided) 90% 97.96 to 103.86 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 5.0 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T2 divided by R2. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FDC 10 Fed (T3), E10+L5+M1000 Fed (R3) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 99.75 | |
| Confidence Interval |
(2-Sided) 90% 95.81 to 103.86 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 6.0 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T3 divided by R3. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
| Title | Area Under the Concentration-time Curve of the Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) |
|---|---|
| Description | Area under the concentration-time curve of the Metformin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented |
| Time Frame | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast |
| Measure Participants | 15 | 14 | 20 | 18 | 14 | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
14100
(29.3)
|
14100
(30.0)
|
8260
(29.2)
|
8600
(33.2)
|
12200
(25.8)
|
12400
(25.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fed (T1), E25+L5+M1000 Fed (R1) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 96.57 | |
| Confidence Interval |
(2-Sided) 90% 90.94 to 102.56 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 8.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T1 divided by R1. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fast (T2), E25+L5+M1000 Fast (R2) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 95.40 | |
| Confidence Interval |
(2-Sided) 90% 87.50 to 104.01 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 14.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T2 divided by R2. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FDC 10 Fed (T3), E10+L5+M1000 Fed (R3) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 98.45 | |
| Confidence Interval |
(2-Sided) 90% 92.44 to 104.85 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 9.4 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T3 divided by R3. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
| Title | Area Under the Concentration-time Curve of the Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) |
|---|---|
| Description | Area under the concentration-time curve of the Linagliptin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented |
| Time Frame | 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast |
| Measure Participants | 15 | 14 | 20 | 18 | 14 | 15 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
465
(27.2)
|
483
(24.8)
|
477
(31.1)
|
443
(25.2)
|
424
(27.6)
|
420
(27.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fed (T1), E25+L5+M1000 Fed (R1) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 95.08 | |
| Confidence Interval |
(2-Sided) 90% 87.36 to 103.48 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 12.6 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T1 divided by R1. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | FDC 25 Fast (T2), E25+L5+M1000 Fast (R2) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 105.72 | |
| Confidence Interval |
(2-Sided) 90% 98.78 to 113.15 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 11.7 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T2 divided by R2. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | FDC 10 Fed (T3), E10+L5+M1000 Fed (R3) |
|---|---|---|
| Comments | The statistical model used was an Analysis of variance (ANOVA) model on the logarithmic scale. This model included 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio (%) |
| Estimated Value | 101.61 | |
| Confidence Interval |
(2-Sided) 90% 92.00 to 112.22 |
|
| Parameter Dispersion |
Type: Standard Deviation Value: 14.9 |
|
| Estimation Comments | Relative bioavailability was estimated by the adjusted gMean ratio of T3 divided by R3. Standard deviation is actually intra-individual geometric coefficient variation (gCV). | |
Adverse Events
| Time Frame | Adverse events occurring up to 168 hours after intake of trial drug administration in each treatment period were assigned to treatment. Adverse events were collected up to 42 days per participant. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) | ||||||
| Arm/Group Description | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 times 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after an overnight fast of at least 10 h | Subjects were orally administered single dose of free combination of 25 mg empagliflozin, 5 mg linagliptin and 2 tablets of 500 mg metformin extended release tablets with 240 mL of water after after an overnight fast of at least 10 h | Subjects were orally administered single dose of 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablet with 240 mL of water after a high-fat, high-calorie breakfast | Subjects were orally administered single dose of free combination of 10 mg empagliflozin, 5 mg linagliptin and 2 tablets of 500 mg metformin extended release tablets with 240 mL of water after a high-fat, high-calorie breakfast | ||||||
All Cause Mortality |
||||||||||||
| FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 0/14 (0%) | 0/20 (0%) | 0/18 (0%) | 0/14 (0%) | 0/15 (0%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| FDC 25 Fed (T1) | E25+L5+M1000 Fed (R1) | FDC 25 Fast (T2) | E25+L5+M1000 Fast (R2) | FDC 10 Fed (T3) | E10+L5+M1000 Fed (R3) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/15 (33.3%) | 4/14 (28.6%) | 6/20 (30%) | 4/18 (22.2%) | 1/14 (7.1%) | 4/15 (26.7%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain upper | 0/15 (0%) | 0/14 (0%) | 1/20 (5%) | 0/18 (0%) | 0/14 (0%) | 1/15 (6.7%) | ||||||
| Diarrhoea | 0/15 (0%) | 0/14 (0%) | 0/20 (0%) | 1/18 (5.6%) | 0/14 (0%) | 2/15 (13.3%) | ||||||
| Nausea | 1/15 (6.7%) | 2/14 (14.3%) | 1/20 (5%) | 0/18 (0%) | 0/14 (0%) | 2/15 (13.3%) | ||||||
| Vomiting | 1/15 (6.7%) | 0/14 (0%) | 0/20 (0%) | 0/18 (0%) | 0/14 (0%) | 0/15 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Nasopharyngitis | 0/15 (0%) | 0/14 (0%) | 0/20 (0%) | 1/18 (5.6%) | 0/14 (0%) | 0/15 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Decreased appetite | 0/15 (0%) | 0/14 (0%) | 0/20 (0%) | 0/18 (0%) | 0/14 (0%) | 1/15 (6.7%) | ||||||
| Nervous system disorders | ||||||||||||
| Dizziness | 1/15 (6.7%) | 1/14 (7.1%) | 1/20 (5%) | 0/18 (0%) | 0/14 (0%) | 1/15 (6.7%) | ||||||
| Headache | 2/15 (13.3%) | 2/14 (14.3%) | 3/20 (15%) | 3/18 (16.7%) | 1/14 (7.1%) | 2/15 (13.3%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Oropharyngeal pain | 0/15 (0%) | 1/14 (7.1%) | 0/20 (0%) | 0/18 (0%) | 0/14 (0%) | 0/15 (0%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Blister rupture | 0/15 (0%) | 1/14 (7.1%) | 0/20 (0%) | 0/18 (0%) | 0/14 (0%) | 0/15 (0%) | ||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Boehringer Ingelheim Call Center |
|---|---|
| Organization | Boehringer Ingelheim |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02821910
Other Study ID Numbers:
- 1361.1
- 2015-005082-23
First Posted:
Jul 4, 2016
Last Update Posted:
Mar 5, 2020
Last Verified:
Feb 1, 2020