Trial Outcomes & Findings for Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Linagliptin Compared With the Free Combination of Empagliflozin Tablet and Linagliptin Tablet in Healthy Male and Female Subjects (NCT NCT02758171)
NCT ID: NCT02758171
Last Updated: 2017-11-22
Results Overview
This outcome measure presents area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point. Time frame description: The time -1:00 hour (h) was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for AUC0-tz (area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point).
COMPLETED
PHASE1
56 participants
1:00 [hour (h): minute] before drug administration and 0:20h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, and 72:00h after drug administration.
2017-11-22
Participant Flow
Participant milestones
| Measure |
FDC/Empagliflozin+Linagliptin
The subjects were administered one FDC (Fixed-Dose Combination) film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T) in period 1, followed by one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) administered orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R) in period 2.
A wash-out period of at least 35 days was set following the drug administration in each period.
|
Empagliflozin+Linagliptin/FDC
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R) in period 1, followed by one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin administered orally with 240 mL of water after an overnight fast of at least 10 h, as a single dose in the fasted state on Day 1 of Test treatment (T) in period 2.
A wash-out period of at least 35 days was set following the drug administration in each period.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
28
|
28
|
|
Treatment Period 1
COMPLETED
|
28
|
28
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
|
Wash-out
STARTED
|
28
|
28
|
|
Wash-out
COMPLETED
|
26
|
28
|
|
Wash-out
NOT COMPLETED
|
2
|
0
|
|
Treatment Period 2
STARTED
|
26
|
28
|
|
Treatment Period 2
COMPLETED
|
26
|
28
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
FDC/Empagliflozin+Linagliptin
The subjects were administered one FDC (Fixed-Dose Combination) film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T) in period 1, followed by one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) administered orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R) in period 2.
A wash-out period of at least 35 days was set following the drug administration in each period.
|
Empagliflozin+Linagliptin/FDC
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R) in period 1, followed by one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin administered orally with 240 mL of water after an overnight fast of at least 10 h, as a single dose in the fasted state on Day 1 of Test treatment (T) in period 2.
A wash-out period of at least 35 days was set following the drug administration in each period.
|
|---|---|---|
|
Wash-out
Withdrawal by Subject
|
1
|
0
|
|
Wash-out
Other reason
|
1
|
0
|
Baseline Characteristics
Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Linagliptin Compared With the Free Combination of Empagliflozin Tablet and Linagliptin Tablet in Healthy Male and Female Subjects
Baseline characteristics by cohort
| Measure |
FDC/Empagliflozin+Linagliptin
n=28 Participants
The subjects were administered one FDC (Fixed-Dose Combination) film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T) in period 1, followed by one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) administered orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R) in period 2.
A wash-out period of at least 35 days was set following the drug administration in each period.
|
Empagliflozin+Linagliptin/FDC
n=28 Participants
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R) in period 1, followed by one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin administered orally with 240 mL of water after an overnight fast of at least 10 h, as a single dose in the fasted state on Day 1 of Test treatment (T) in period 2.
A wash-out period of at least 35 days was set following the drug administration in each period.
|
Total
n=56 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.1 Years
STANDARD_DEVIATION 9.7 • n=5 Participants
|
38.9 Years
STANDARD_DEVIATION 10.2 • n=7 Participants
|
39.0 Years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1:00 [hour (h): minute] before drug administration and 0:20h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, and 72:00h after drug administration.Population: PharmacoKinetic parameter analysis Set (PKS): This subject set included all subjects from the TS who provided at least 1 primary or secondary PK parameter that was judged as PK evaluable and not affected by protocol violations relevant to the evaluation of PK parameters.
This outcome measure presents area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point. Time frame description: The time -1:00 hour (h) was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for AUC0-tz (area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point).
Outcome measures
| Measure |
FDC (10 mg Empagliflozin and 5 mg Linagliptin)
n=55 Participants
The subjects were administered one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T).
|
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets
n=54 Participants
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R).
|
|---|---|---|
|
AUC0-tz (Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point)
|
2550 nmol*h/L
Geometric Coefficient of Variation 18.0
|
2510 nmol*h/L
Geometric Coefficient of Variation 19.9
|
PRIMARY outcome
Timeframe: 1:00 [hour (h): minute] before drug administration and 0:20h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, and 72:00h after drug administration.Population: PharmacoKinetic parameter analysis Set (PKS): This subject set included all subjects from the TS who provided at least 1 primary or secondary PK parameter that was judged as PK evaluable and not affected by protocol violations relevant to the evaluation of PK parameters.
This outcome measure presents area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 to 72 hours. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for AUC0-72 (area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 to 72 hours).
Outcome measures
| Measure |
FDC (10 mg Empagliflozin and 5 mg Linagliptin)
n=55 Participants
The subjects were administered one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T).
|
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets
n=54 Participants
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R).
|
|---|---|---|
|
AUC0-72 (Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours)
|
281 nmol*h/L
Geometric Coefficient of Variation 22.5
|
283 nmol*h/L
Geometric Coefficient of Variation 23.3
|
PRIMARY outcome
Timeframe: 1:00 [hour (h): minute] before drug administration and 0:20h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, and 72:00h after drug administration.Population: PharmacoKinetic parameter analysis Set (PKS): This subject set included all subjects from the TS who provided at least 1 primary or secondary PK parameter that was judged as PK evaluable and not affected by protocol violations relevant to the evaluation of PK parameters.
This outcome measure presents maximum measured concentration of Empagliflozin analyte in plasma. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for Cmax (maximum measured concentration of Empagliflozin analyte in plasma).
Outcome measures
| Measure |
FDC (10 mg Empagliflozin and 5 mg Linagliptin)
n=55 Participants
The subjects were administered one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T).
|
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets
n=54 Participants
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R).
|
|---|---|---|
|
Cmax (Maximum Measured Concentration of Empagliflozin Analyte in Plasma)
|
370 nmol/L
Geometric Coefficient of Variation 23.9
|
365 nmol/L
Geometric Coefficient of Variation 23.9
|
PRIMARY outcome
Timeframe: 1:00 [hour (h): minute] before drug administration and 0:20h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, and 72:00h after drug administration.Population: PharmacoKinetic parameter analysis Set (PKS): This subject set included all subjects from the TS who provided at least 1 primary or secondary PK parameter that was judged as PK evaluable and not affected by protocol violations relevant to the evaluation of PK parameters.
This outcome measure presents maximum measured concentration of Linagliptin analyte in plasma. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for Cmax (maximum measured concentration of Linagliptin analyte in plasma).
Outcome measures
| Measure |
FDC (10 mg Empagliflozin and 5 mg Linagliptin)
n=55 Participants
The subjects were administered one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T).
|
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets
n=54 Participants
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R).
|
|---|---|---|
|
Cmax (Maximum Measured Concentration of Linagliptin Analyte in Plasma)
|
9.33 nmol/L
Geometric Coefficient of Variation 36.2
|
8.73 nmol/L
Geometric Coefficient of Variation 37.1
|
SECONDARY outcome
Timeframe: 1:00 [hour (h): minute] before drug administration and 0:20h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, and 72:00h after drug administration.Population: PharmacoKinetic parameter analysis Set (PKS): This subject set included all subjects from the TS who provided at least 1 primary or secondary PK parameter that was judged as PK evaluable and not affected by protocol violations relevant to the evaluation of PK parameters.
This outcome measure presents area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 extrapolated to infinity. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for AUC0-infinity (area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 extrapolated to infinity).
Outcome measures
| Measure |
FDC (10 mg Empagliflozin and 5 mg Linagliptin)
n=55 Participants
The subjects were administered one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T).
|
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets
n=54 Participants
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R).
|
|---|---|---|
|
AUC0-infinity (Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
|
2580 nmol*h/L
Geometric Coefficient of Variation 18.0
|
2550 nmol*h/L
Geometric Coefficient of Variation 19.8
|
SECONDARY outcome
Timeframe: 1:00 [hour (h): minute] before drug administration and 0:20h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, and 72:00h after drug administration.Population: PharmacoKinetic parameter analysis Set (PKS): This subject set included all subjects from the TS who provided at least 1 primary or secondary PK parameter that was judged as PK evaluable and not affected by protocol violations relevant to the evaluation of PK parameters.
This outcome measure presents area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 extrapolated to infinity. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for (area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 extrapolated to infinity).
Outcome measures
| Measure |
FDC (10 mg Empagliflozin and 5 mg Linagliptin)
n=55 Participants
The subjects were administered one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T).
|
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets
n=54 Participants
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R).
|
|---|---|---|
|
AUC0-infinity (Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
|
451 nmol*h/L
Geometric Coefficient of Variation 25.9
|
462 nmol*h/L
Geometric Coefficient of Variation 29.2
|
Adverse Events
FDC (10 mg Empagliflozin and 5 mg Linagliptin)
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
FDC (10 mg Empagliflozin and 5 mg Linagliptin)
n=56 participants at risk
The subjects were administered one FDC film-coated tablet containing 10 mg Empagliflozin and 5 mg Linagliptin orally with 240 mL of water after an overnight fast of at least 10 hours (h), as a single dose in the fasted state on Day 1 of Test treatment (T).
|
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets
n=54 participants at risk
The subjects were administered one film-coated tablet containing 10 mg Empagliflozin (reference product 1) in combination with 1 film-coated tablet containing 5 mg Linagliptin (reference product 2) orally with 240 mL of water after an overnight fast of at least 10 h, as single doses in the fasted state on Day 1 of Reference treatment (R).
|
|---|---|---|
|
Nervous system disorders
Headache
|
14.3%
8/56 • From first drug administration until 1 day after last drug administration, up to 77 days.
|
13.0%
7/54 • From first drug administration until 1 day after last drug administration, up to 77 days.
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place