Trial Outcomes & Findings for Bioequivalence Study in Healthy Volunteers for Empagliflozin/Metformin Fixed Dose Combination Compared to Separate Tablets (NCT NCT02028767)
NCT ID: NCT02028767
Last Updated: 2015-07-24
Results Overview
AUC (0-tz) (area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Results posted on
2015-07-24
Participant Flow
Participant milestones
| Measure |
Fixed Dose Combination (FDC) First, Then Separate Tablets
Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin first,
then free combination of Empagliflozin 2.5 mg tablet, Empagliflozin 10 mg tablet and Metformin 500 mg tablet
Both medications were administered oral with 240 mL water after intake of a high-fat, high-calorie meal.
|
Separate Tablets First, Then Fixed Dose Combination (FDC)
free combination of Empagliflozin 2.5 mg tablet, Empagliflozin 10 mg tablet and Metformin 500 mg tablet first,
then Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin
Both medications were administered oral with 240 mL water after intake of a high-fat, high-calorie meal.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
16
|
16
|
|
Treatment Period 1
COMPLETED
|
16
|
16
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2
STARTED
|
16
|
16
|
|
Treatment Period 2
COMPLETED
|
14
|
16
|
|
Treatment Period 2
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Fixed Dose Combination (FDC) First, Then Separate Tablets
Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin first,
then free combination of Empagliflozin 2.5 mg tablet, Empagliflozin 10 mg tablet and Metformin 500 mg tablet
Both medications were administered oral with 240 mL water after intake of a high-fat, high-calorie meal.
|
Separate Tablets First, Then Fixed Dose Combination (FDC)
free combination of Empagliflozin 2.5 mg tablet, Empagliflozin 10 mg tablet and Metformin 500 mg tablet first,
then Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin
Both medications were administered oral with 240 mL water after intake of a high-fat, high-calorie meal.
|
|---|---|---|
|
Treatment Period 2
Non compliant with protocol
|
1
|
0
|
|
Treatment Period 2
Reason other than those specified above
|
1
|
0
|
Baseline Characteristics
Bioequivalence Study in Healthy Volunteers for Empagliflozin/Metformin Fixed Dose Combination Compared to Separate Tablets
Baseline characteristics by cohort
| Measure |
Fixed Dose Combination vs. Separate Tablets
n=32 Participants
12.5 mg Empagliflozin / 500mg metformin fixed dose combination vs. free combination of 2.5 mg tablet Empagliflozin, 10 mg tablet Empagliflozin and 500 mg tablet Metformin
|
|---|---|
|
Age, Continuous
|
36.1 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administrationPopulation: Pharmacokinetic set (PKS): includes all subjects of the TS who provided at least 1 observation for at least 1 primary pharmacokinetic endpoint, and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints.
AUC (0-tz) (area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point)
Outcome measures
| Measure |
Fixed Dose Combination (FDC)
n=32 Participants
12.5 mg Empagliflozin / 500mg metformin fixed dose combination
Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin
|
Separate Tablets
n=30 Participants
Empagliflozin and Metformin tablets
Empagliflozin 2.5 mg: Empagliflozin 2.5 mg tablet
Empagliflozin 10 mg: Empagliflozin 10 mg tablet
Metformin 500 mg: Metformin 500 mg tablet
|
|---|---|---|
|
AUC (0-tz) (Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point)
|
6260 ng*h/mL
Geometric Coefficient of Variation 20.4
|
6360 ng*h/mL
Geometric Coefficient of Variation 21.8
|
PRIMARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administrationPopulation: PKS: includes all subjects of the TS who provided at least 1 observation for at least 1 primary pharmacokinetic endpoint, and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints.
Cmax (maximum measured concentration of metformin in plasma)
Outcome measures
| Measure |
Fixed Dose Combination (FDC)
n=32 Participants
12.5 mg Empagliflozin / 500mg metformin fixed dose combination
Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin
|
Separate Tablets
n=30 Participants
Empagliflozin and Metformin tablets
Empagliflozin 2.5 mg: Empagliflozin 2.5 mg tablet
Empagliflozin 10 mg: Empagliflozin 10 mg tablet
Metformin 500 mg: Metformin 500 mg tablet
|
|---|---|---|
|
Cmax (Maximum Measured Concentration of Metformin in Plasma)
|
746 ng/mL
Geometric Coefficient of Variation 21.3
|
754 ng/mL
Geometric Coefficient of Variation 23.3
|
SECONDARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administrationPopulation: PKS: includes all subjects of the TS who provided at least 1 observation for at least 1 primary pharmacokinetic endpoint, and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints.
AUC (0-infinity) (Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity)
Outcome measures
| Measure |
Fixed Dose Combination (FDC)
n=32 Participants
12.5 mg Empagliflozin / 500mg metformin fixed dose combination
Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin
|
Separate Tablets
n=30 Participants
Empagliflozin and Metformin tablets
Empagliflozin 2.5 mg: Empagliflozin 2.5 mg tablet
Empagliflozin 10 mg: Empagliflozin 10 mg tablet
Metformin 500 mg: Metformin 500 mg tablet
|
|---|---|---|
|
AUC (0-infinity) (Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
|
6410 ng*h/mL
Geometric Coefficient of Variation 20.9
|
6520 ng*h/mL
Geometric Coefficient of Variation 22.5
|
Adverse Events
Fixed Dose Combination (FDC)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Separate Tablets
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Fixed Dose Combination (FDC)
n=32 participants at risk
12.5 mg Empagliflozin / 500mg metformin fixed dose combination
Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin
|
Separate Tablets
n=30 participants at risk
Empagliflozin and Metformin tablets
Empagliflozin 2.5 mg: Empagliflozin 2.5 mg tablet
Empagliflozin 10 mg: Empagliflozin 10 mg tablet
Metformin 500 mg: Metformin 500 mg tablet
|
|---|---|---|
|
Nervous system disorders
Somnolence
|
21.9%
7/32 • From first trial medication intake until next intake or the day after the end-of-trial visit, 16 days
|
13.3%
4/30 • From first trial medication intake until next intake or the day after the end-of-trial visit, 16 days
|
|
Nervous system disorders
Headache
|
12.5%
4/32 • From first trial medication intake until next intake or the day after the end-of-trial visit, 16 days
|
3.3%
1/30 • From first trial medication intake until next intake or the day after the end-of-trial visit, 16 days
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
2/32 • From first trial medication intake until next intake or the day after the end-of-trial visit, 16 days
|
0.00%
0/30 • From first trial medication intake until next intake or the day after the end-of-trial visit, 16 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Other - 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.
- Publication restrictions are in place
Restriction type: OTHER