Trial Outcomes & Findings for Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Metformin Extended Release Compared With Mono Compound Tablets in Healthy Subjects (NCT NCT02230995)
NCT ID: NCT02230995
Last Updated: 2017-03-09
Results Overview
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)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration
Results posted on
2017-03-09
Participant Flow
This was an open-label, randomised, 2-way crossover trial with 2 treatments (T and R) and 2 treatment sequences (T\_R and R\_T). Trial drug administrations of the 2 single dose treatments were separated by a washout period of at least 7 days.
Participant milestones
| Measure |
Fed 25mg+1000mg FDC/Single
Subjects received in period 1 a single dose of 25 mg empagliflozin/1000 mg metformin HCl XR (1 FDC tablet) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
2 treatments separated by a wash-out period of at least 7 days.
|
Fed 25mg+1000mg Single/FDC
Subjects received in period 1 a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 25 mg empagliflozin/1000 mg metformin HCl XR (1 FDC tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
2 treatments separated by a wash-out period of at least 7 days.
|
|---|---|---|
|
Period 1 + Washout
STARTED
|
15
|
15
|
|
Period 1 + Washout
COMPLETED
|
15
|
15
|
|
Period 1 + Washout
NOT COMPLETED
|
0
|
0
|
|
Period 2 + Washout
STARTED
|
15
|
15
|
|
Period 2 + Washout
COMPLETED
|
15
|
15
|
|
Period 2 + Washout
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Metformin Extended Release Compared With Mono Compound Tablets in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Fed 25mg+1000mg FDC/Single
n=15 Participants
Subjects received in period 1 a single dose of 25 mg empagliflozin/1000 mg metformin HCl XR (1 FDC tablet) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
2 treatments separated by a wash-out period of at least 7 days.
|
Fed 25mg+1000mg Single/FDC
n=15 Participants
Subjects received in period 1 a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 25 mg empagliflozin/1000 mg metformin HCl XR (1 FDC tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
2 treatments separated by a wash-out period of at least 7 days.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36.60 Years
STANDARD_DEVIATION 9.30 • n=5 Participants
|
32.00 Years
STANDARD_DEVIATION 9.80 • n=7 Participants
|
34.30 Years
STANDARD_DEVIATION 9.70 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationPopulation: PKS set
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)
Outcome measures
| Measure |
Fed 25mg+1000mg FDC
n=30 Participants
Subjects received a single dose of 25 mg empagliflozin/1000 mg metformin Hydrochloride (HCl) Extended release (XR) (1 Fixed dose combination (FDC) tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
Fed 25mg+1000mg Single
n=30 Participants
Subject received a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
|---|---|---|
|
AUC0-tz of Empagliflozin in Plasma
|
5370 nmol·h/L
Geometric Coefficient of Variation 14.9
|
5470 nmol·h/L
Geometric Coefficient of Variation 16.0
|
PRIMARY outcome
Timeframe: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationPopulation: Pharmacokinetic Set (PKS): This analysis set included all treated subjects that provided at least 1 observation for at least 1 primary endpoint without important protocol violations with respect to the statistical evaluation of the pharmacokinetic endpoints.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable concentration
Outcome measures
| Measure |
Fed 25mg+1000mg FDC
n=30 Participants
Subjects received a single dose of 25 mg empagliflozin/1000 mg metformin Hydrochloride (HCl) Extended release (XR) (1 Fixed dose combination (FDC) tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
Fed 25mg+1000mg Single
n=30 Participants
Subject received a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
|---|---|---|
|
AUC0-tz of Metformin in Plasma
|
11000 ng·h/mL
Geometric Coefficient of Variation 21.5
|
10800 ng·h/mL
Geometric Coefficient of Variation 22.8
|
PRIMARY outcome
Timeframe: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationPopulation: PKS set
Maximum measured concentration of empagliflozin in plasma (Cmax)
Outcome measures
| Measure |
Fed 25mg+1000mg FDC
n=30 Participants
Subjects received a single dose of 25 mg empagliflozin/1000 mg metformin Hydrochloride (HCl) Extended release (XR) (1 Fixed dose combination (FDC) tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
Fed 25mg+1000mg Single
n=30 Participants
Subject received a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
|---|---|---|
|
Cmax of Empagliflozin in Plasma
|
590 nmol/L
Geometric Coefficient of Variation 19.9
|
597 nmol/L
Geometric Coefficient of Variation 19.5
|
PRIMARY outcome
Timeframe: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationPopulation: PKS set
Maximum measured concentration of the metformin in plasma
Outcome measures
| Measure |
Fed 25mg+1000mg FDC
n=30 Participants
Subjects received a single dose of 25 mg empagliflozin/1000 mg metformin Hydrochloride (HCl) Extended release (XR) (1 Fixed dose combination (FDC) tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
Fed 25mg+1000mg Single
n=30 Participants
Subject received a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
|---|---|---|
|
Cmax of Metformin in Plasma
|
1120 ng/mL
Geometric Coefficient of Variation 23.0
|
1060 ng/mL
Geometric Coefficient of Variation 24.9
|
SECONDARY outcome
Timeframe: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationPopulation: PKS set
Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity)
Outcome measures
| Measure |
Fed 25mg+1000mg FDC
n=30 Participants
Subjects received a single dose of 25 mg empagliflozin/1000 mg metformin Hydrochloride (HCl) Extended release (XR) (1 Fixed dose combination (FDC) tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
Fed 25mg+1000mg Single
n=30 Participants
Subject received a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
|---|---|---|
|
AUC0-infinity of Empagliflozin in Plasma
|
5460 nmol·h/L
Geometric Coefficient of Variation 15.1
|
5550 nmol·h/L
Geometric Coefficient of Variation 16.2
|
SECONDARY outcome
Timeframe: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationPopulation: PKS set
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Outcome measures
| Measure |
Fed 25mg+1000mg FDC
n=30 Participants
Subjects received a single dose of 25 mg empagliflozin/1000 mg metformin Hydrochloride (HCl) Extended release (XR) (1 Fixed dose combination (FDC) tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
Fed 25mg+1000mg Single
n=30 Participants
Subject received a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
|---|---|---|
|
AUC0-infinity of Metformin in Plasma
|
11500 ng*h/mL
Geometric Coefficient of Variation 20.2
|
11000 ng*h/mL
Geometric Coefficient of Variation 22.7
|
Adverse Events
Fed 25mg+1000mg FDC
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Fed 25mg+1000mg Single
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 |
Fed 25mg+1000mg FDC
n=30 participants at risk
Subjects received a single dose of 25 mg empagliflozin/1000 mg metformin Hydrochloride (HCl) Extended release (XR) (1 Fixed dose combination (FDC) tablet) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
Fed 25mg+1000mg Single
n=30 participants at risk
Subject received a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal.
|
|---|---|---|
|
Nervous system disorders
Nasopharyngitis
|
6.7%
2/30 • From first drug administration up to 13 days after last drug administration, ie., upto 20 days.
|
0.00%
0/30 • From first drug administration up to 13 days after last drug administration, ie., upto 20 days.
|
|
Nervous system disorders
Headache
|
6.7%
2/30 • From first drug administration up to 13 days after last drug administration, ie., upto 20 days.
|
10.0%
3/30 • From first drug administration up to 13 days after last drug administration, ie., upto 20 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.3%
1/30 • From first drug administration up to 13 days after last drug administration, ie., upto 20 days.
|
6.7%
2/30 • From first drug administration up to 13 days after last drug administration, ie., upto 20 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
- Publication restrictions are in place