Trial Outcomes & Findings for A Study in Healthy Humans to Assess the Relative Bioavailability of One Fixed-dose Combination Tablet Empagliflozin/Metformin Versus Jardiance® Tablet and Glifage® Tablet Administered Together (NCT NCT05083949)
NCT ID: NCT05083949
Last Updated: 2023-07-27
Results Overview
Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) normalized to the actual administered dose is presented. The AUC0-tz was divided by the actual dose strength to get the normalized area under the concentration-time curve. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. 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. Unit of measure:(hour\*nanogram/milliliter)/milligram.
COMPLETED
PHASE1
32 participants
Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
2023-07-27
Participant Flow
This was a phase I, randomised, open label, 2x2 crossover trial in healthy male and female subjects to establish the bioequivalence of 1 Fixed dose combination tablet 12.5 mg empagliflozin/850 mg metformin (treatment B) to the reference treatments (treatment A) which consisted in 1 tablet empagliflozin10 mg (Reference 1) + 1 tablet Glifage® 850 mg (Reference 2).
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participant milestones
| Measure |
(A): Empagliflozin 10mg (R1)+Glifage® 850mg (R2),Then (B): FDC 12.5mg Empagliflozin/850mg Metformin
On Day 1 of Period 1 participants received treatment A: Single dose tablet of 10 milligram(mg) empagliflozin film-coated and a 850mg of metformin hydrochloride (HCl) (Glifage®) tablet, orally with 200 milliliter(mL) of water.
On Day 1 of Period 2 participants received treatment B: Fixed dose combination (FDC) tablet of 12.5mg empagliflozin/850 mg metformin HCl, orally with 200mL of water.
A high-fat, high-calorie meal was served 30 minutes(min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin,Then (A): Empagliflozin 10mg(R1) + Glifage® 850mg(R2)
On Day 1 of Period 1 participants received treatment B: Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin hydrochloride (HCl), orally with 200 milliliter (mL) of water.
On Day 1 of Period 2 participants received treatment A: Single dose tablet of 10mg empagliflozin and 850 mg of metformin HCl (Glifage®) tablet, orally with 200mL of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days.
|
|---|---|---|
|
Period 1
STARTED
|
16
|
16
|
|
Period 1
COMPLETED
|
13
|
14
|
|
Period 1
NOT COMPLETED
|
3
|
2
|
|
Wash-out
STARTED
|
13
|
14
|
|
Wash-out
COMPLETED
|
13
|
14
|
|
Wash-out
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
13
|
14
|
|
Period 2
COMPLETED
|
12
|
12
|
|
Period 2
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
(A): Empagliflozin 10mg (R1)+Glifage® 850mg (R2),Then (B): FDC 12.5mg Empagliflozin/850mg Metformin
On Day 1 of Period 1 participants received treatment A: Single dose tablet of 10 milligram(mg) empagliflozin film-coated and a 850mg of metformin hydrochloride (HCl) (Glifage®) tablet, orally with 200 milliliter(mL) of water.
On Day 1 of Period 2 participants received treatment B: Fixed dose combination (FDC) tablet of 12.5mg empagliflozin/850 mg metformin HCl, orally with 200mL of water.
A high-fat, high-calorie meal was served 30 minutes(min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin,Then (A): Empagliflozin 10mg(R1) + Glifage® 850mg(R2)
On Day 1 of Period 1 participants received treatment B: Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin hydrochloride (HCl), orally with 200 milliliter (mL) of water.
On Day 1 of Period 2 participants received treatment A: Single dose tablet of 10mg empagliflozin and 850 mg of metformin HCl (Glifage®) tablet, orally with 200mL of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days.
|
|---|---|---|
|
Period 1
Positive doping for Tetrahydrocannabinol (THC)
|
2
|
1
|
|
Period 1
Adverse Event
|
1
|
1
|
|
Period 2
The patient was not able to eat the full content of the breakfast
|
1
|
0
|
|
Period 2
Adverse Event
|
0
|
2
|
Baseline Characteristics
A Study in Healthy Humans to Assess the Relative Bioavailability of One Fixed-dose Combination Tablet Empagliflozin/Metformin Versus Jardiance® Tablet and Glifage® Tablet Administered Together
Baseline characteristics by cohort
| Measure |
(A): Empagliflozin 10mg (R1)+Glifage® 850mg (R2),Then (B): FDC 12.5mg Empagliflozin/850mg Metformin
n=16 Participants
On Day 1 of Period 1 participants received treatment A: Single dose tablet of 10 milligram(mg) empagliflozin film-coated and a 850mg of metformin hydrochloride (HCl) (Glifage®) tablet, orally with 200 milliliter(mL) of water.
On Day 1 of Period 2 participants received treatment B: Fixed dose combination (FDC) tablet of 12.5mg empagliflozin/850 mg metformin HCl, orally with 200mL of water.
A high-fat, high-calorie meal was served 30 minutes(min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin,Then (A): Empagliflozin 10mg(R1) + Glifage® 850mg(R2)
n=16 Participants
On Day 1 of Period 1 participants received treatment B: Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin hydrochloride (HCl), orally with 200 milliliter (mL) of water.
On Day 1 of Period 2 participants received treatment A: Single dose tablet of 10mg empagliflozin and 850 mg of metformin HCl (Glifage®) tablet, orally with 200mL of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days.
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
32.0 Years
STANDARD_DEVIATION 7.2 • n=39 Participants
|
31.7 Years
STANDARD_DEVIATION 8.3 • n=41 Participants
|
31.8 Years
STANDARD_DEVIATION 7.9 • n=35 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
16 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
16 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
5 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=39 Participants
|
11 Participants
n=41 Participants
|
18 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
6 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
9 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) normalized to the actual administered dose is presented. The AUC0-tz was divided by the actual dose strength to get the normalized area under the concentration-time curve. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. 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. Unit of measure:(hour\*nanogram/milliliter)/milligram.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
|
117.15 (h*ng/mL)/mg
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.04.
|
116.65 (h*ng/mL)/mg
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.04.
|
PRIMARY outcome
Timeframe: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
Dose-normalized Maximum measured concentration of empagliflozin in plasma is presented. The maximum measured concentration was divided by the actual dose strength to get the dose-normalised Cmax. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. 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. The unit of measure reported is: (nanogram/milliliter)/milligram.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Dose-normalized Maximum Measured Concentration of Empagliflozin (Cmax)
|
13.42 (ng/mL)/mg
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.03.
|
13.60 (ng/mL)/mg
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.03.
|
PRIMARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. 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.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
|
10299.45 hour*nanogram/milliliter (h*ng/mL)
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.05.
|
10467.41 hour*nanogram/milliliter (h*ng/mL)
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.05.
|
PRIMARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
Maximum measured concentration of metformin in plasma is presented. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. 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.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Maximum Measured Concentration of Metformin (Cmax)
|
1333.58 nanogram/milliliter (ng/mL )
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.04.
|
1308.39 nanogram/milliliter (ng/mL )
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.04.
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 extrapolated to infinity from the last quantifiable data point (AUC0-inf) normalized to the actual administered dose is presented. The AUC0-oo was divided by the actual dose strength to get the normalized area under the concentration-time curve. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. 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. Unit of measure: (hour\*nanogram/milliliter)/milligram.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ )
|
118.25 (h*ng/mL)/mg
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.03.
|
117.64 (h*ng/mL)/mg
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.03.
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞ ) is presented. The statistical model used for the analysis was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. 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.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
|
10440.79 hour*nanogram/milliliter (hr*ng/mL)
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.05.
|
10570.45 hour*nanogram/milliliter (hr*ng/mL)
Standard Error NA
The standard error is actually the geometric standard error and is equal to 1.05.
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
Time from last dosing to the maximum measured concentration of empagliflozin in plasma (tmax) is presented.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Time From Last Dosing to the Maximum Measured Concentration of Empagliflozin in Plasma (Tmax)
|
2.33 Hours (hr)
Interval 1.25 to 5.0
|
2.17 Hours (hr)
Interval 1.0 to 5.5
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
Time from last dosing to the maximum measured concentration of metformin in plasma (tmax) is presented.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Time From Last Dosing to the Maximum Measured Concentration of Metformin in Plasma (Tmax)
|
4.00 Hours (hr)
Interval 3.0 to 4.5
|
4.00 Hours (hr)
Interval 1.0 to 5.0
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
The percentage (%) of the AUC of empagliflozin that has been derived after extrapolation is reported.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Percentage (%) of the AUC of Empagliflozin That Has Been Derived After Extrapolation
|
9.77 Percentage (%)
Standard Deviation 3.04
|
9.31 Percentage (%)
Standard Deviation 1.87
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
The percentage (%) of the AUC of metformin that has been derived after extrapolation is reported.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Percentage (%) of the AUC of Metformin That Has Been Derived After Extrapolation
|
14.35 Percentage (%)
Standard Deviation 8.50
|
13.04 Percentage (%)
Standard Deviation 5.58
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
The terminal half-life of empagliflozin in plasma (t1/2) is presented.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Terminal Half-life of Empagliflozin in Plasma (t1/2)
|
0.08 Hours (hr)
Interval 0.04 to 0.11
|
0.08 Hours (hr)
Interval 0.05 to 0.11
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
The terminal half-life of metformin in plasma (t1/2) is presented.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Terminal Half-life of Metformin in Plasma (t1/2)
|
0.06 Hours (hr)
Interval 0.02 to 0.13
|
0.06 Hours (hr)
Interval 0.02 to 0.11
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
The elimination rate constant (Kel) for empagliflozin is reported.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Elimination Rate Constant (Kel) for Empagliflozin
|
0.93 1/hours (1/hr)
Standard Deviation 0.61
|
0.84 1/hours (1/hr)
Standard Deviation 0.44
|
SECONDARY outcome
Timeframe: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.
The elimination rate constant (Kel) for metformin is reported.
Outcome measures
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=24 Participants
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=24 Participants
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Elimination Rate Constant (Kel) for Metformin
|
1.33 1/hours (1/hr)
Standard Deviation 2.14
|
0.97 1/hours (1/hr)
Standard Deviation 1.02
|
Adverse Events
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
(B): FDC 12.5mg Empagliflozin/850mg Metformin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)
n=30 participants at risk
Participants received treatment A: Single dose tablet of 10 milligram (mg) empagliflozin film-coated and a 850mg of metformin HCl (Glifage®) tablet, orally with 200 milliliter (mL) of water.
A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
(B): FDC 12.5mg Empagliflozin/850mg Metformin
n=29 participants at risk
Participants were administered the treatment B which consisted of a single Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration.
|
|---|---|---|
|
Investigations
White blood cells in urine
|
10.0%
3/30 • Up to 14 days after the last treatment administration.
Treated Set (TS): The treated set included all participants in the research that were randomized and treated with at least one dose of study medication.
|
0.00%
0/29 • Up to 14 days after the last treatment administration.
Treated Set (TS): The treated set included all participants in the research that were randomized and treated with at least one dose of study medication.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.7%
2/30 • Up to 14 days after the last treatment administration.
Treated Set (TS): The treated set included all participants in the research that were randomized and treated with at least one dose of study medication.
|
0.00%
0/29 • Up to 14 days after the last treatment administration.
Treated Set (TS): The treated set included all participants in the research that were randomized and treated with at least one dose of study medication.
|
|
Nervous system disorders
Headache
|
3.3%
1/30 • Up to 14 days after the last treatment administration.
Treated Set (TS): The treated set included all participants in the research that were randomized and treated with at least one dose of study medication.
|
6.9%
2/29 • Up to 14 days after the last treatment administration.
Treated Set (TS): The treated set included all participants in the research that were randomized and treated with at least one dose of study medication.
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee 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