Trial Outcomes & Findings for Bioequivalence of Metformin Under Fed Conditions After Administration of Linagliptin / Metformin Fixed Dose Combination Tablet and Single Tablets (NCT NCT01581931)
NCT ID: NCT01581931
Last Updated: 2013-08-20
Results Overview
AUC0-tz represents the area under the concentration curve of metformin in plasma from 0 to the time of the last quantifiable plasma contentration of the analyte. Note, the geometric mean is actually an adjusted geometric mean.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
0:20, 0:40, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 24, 34, 48, 72 hours
Results posted on
2013-08-20
Participant Flow
Participant milestones
| Measure |
Lina+Met Single Tablets / Lina+Met FDC Tablet
Subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets in the first period. After a washout period of at least 35 days, the subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet in period 2.
|
Lina+Met FDC Tablet / Lina+Met Single Tablets
Subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet in the first period. After a washout period of at least 35 days, the subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets in period 2.
|
|---|---|---|
|
First Period
STARTED
|
16
|
16
|
|
First Period
COMPLETED
|
16
|
16
|
|
First Period
NOT COMPLETED
|
0
|
0
|
|
Washout
STARTED
|
16
|
16
|
|
Washout
COMPLETED
|
16
|
15
|
|
Washout
NOT COMPLETED
|
0
|
1
|
|
Second Period
STARTED
|
16
|
15
|
|
Second Period
COMPLETED
|
16
|
15
|
|
Second Period
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Lina+Met Single Tablets / Lina+Met FDC Tablet
Subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets in the first period. After a washout period of at least 35 days, the subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet in period 2.
|
Lina+Met FDC Tablet / Lina+Met Single Tablets
Subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet in the first period. After a washout period of at least 35 days, the subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets in period 2.
|
|---|---|---|
|
Washout
Adverse Event
|
0
|
1
|
Baseline Characteristics
Bioequivalence of Metformin Under Fed Conditions After Administration of Linagliptin / Metformin Fixed Dose Combination Tablet and Single Tablets
Baseline characteristics by cohort
| Measure |
Overall Study
n=32 Participants
This was an open-label, randomised, single dose, 2-way crossover trial with 2 treatments and 2 treatment sequences. The single dose administrations in each treatment period were separated by a washout period of at least 35 days.
|
|---|---|
|
Age Continuous
|
38.8 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0:20, 0:40, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 24, 34, 48, 72 hoursPopulation: Treated set - all subjects taking at least 1 dose of trial medication
AUC0-tz represents the area under the concentration curve of metformin in plasma from 0 to the time of the last quantifiable plasma contentration of the analyte. Note, the geometric mean is actually an adjusted geometric mean.
Outcome measures
| Measure |
Lina+Met Single Tablets
n=30 Participants
Subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets
|
Lina+Met FDC Tablet
n=32 Participants
Subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet
|
|---|---|---|
|
Area Under Curve From 0 to tz Hours (AUC0-tz) of Metformin
|
7219.03 ng·h/mL
Geometric Coefficient of Variation 9.8
|
7057.52 ng·h/mL
Geometric Coefficient of Variation 9.8
|
PRIMARY outcome
Timeframe: 0:20, 0:40, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 24, 34, 48, 72 hoursPopulation: Treated set - all subjects taking at least 1 dose of trial medication
Cmax represents the maximum concentration of metformin in plasma. Note, the geometric mean is actually an adjusted geometric mean.
Outcome measures
| Measure |
Lina+Met Single Tablets
n=30 Participants
Subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets
|
Lina+Met FDC Tablet
n=32 Participants
Subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet
|
|---|---|---|
|
Maximum Concentration (Cmax) of Metformin
|
855.09 ng/mL
Geometric Coefficient of Variation 10.0
|
844.72 ng/mL
Geometric Coefficient of Variation 10.0
|
SECONDARY outcome
Timeframe: 0:20, 0:40, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 24, 34, 48, 72 hoursPopulation: Treated set - all subjects taking at least 1 dose of trial medication
AUC0-infty represents the area under the concentration curve of metformin in plasma from time 0 extrapolated to infinity. Note, the geometric mean is actually an adjusted geometric mean.
Outcome measures
| Measure |
Lina+Met Single Tablets
n=30 Participants
Subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets
|
Lina+Met FDC Tablet
n=32 Participants
Subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet
|
|---|---|---|
|
Area Under Curve From 0 to Infinity Hours (AUC0-infty) of Metformin
|
7343.59 ng·h/mL
Geometric Coefficient of Variation 9.7
|
7174.30 ng·h/mL
Geometric Coefficient of Variation 9.7
|
SECONDARY outcome
Timeframe: 0:20, 0:40, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 24, 34, 48, 72 hoursPopulation: Treated set - all subjects taking at least 1 dose of trial medication
Time from dosing to the maximum concentration of metformin in plasma.
Outcome measures
| Measure |
Lina+Met Single Tablets
n=30 Participants
Subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets
|
Lina+Met FDC Tablet
n=32 Participants
Subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet
|
|---|---|---|
|
Time to Maximum Concentration (Tmax) of Metformin
|
4.00 Hours
Interval 2.0 to 6.0
|
4.00 Hours
Interval 1.0 to 6.0
|
SECONDARY outcome
Timeframe: 0:20, 0:40, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 24, 34, 48, 72 hoursPopulation: Treated set - all subjects taking at least 1 dose of trial medication
The terminal half-life of metformin in plasma is denoted by t1/2.
Outcome measures
| Measure |
Lina+Met Single Tablets
n=30 Participants
Subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets
|
Lina+Met FDC Tablet
n=32 Participants
Subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet
|
|---|---|---|
|
Terminal Half-life t1/2 of Metformin
|
9.14 Hours
Geometric Coefficient of Variation 87.4
|
8.03 Hours
Geometric Coefficient of Variation 86.0
|
Adverse Events
Lina+Met Single Tablets
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Lina+Met FDC Tablet
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lina+Met Single Tablets
n=31 participants at risk
Subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets
|
Lina+Met FDC Tablet
n=32 participants at risk
Subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet
|
|---|---|---|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/31 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
3.1%
1/32 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/31 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
3.1%
1/32 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
Other adverse events
| Measure |
Lina+Met Single Tablets
n=31 participants at risk
Subjects are treated with single linagliptin 2.5 mg and metformin 500 mg tablets
|
Lina+Met FDC Tablet
n=32 participants at risk
Subjects are treated with a 2.5 mg linagliptin / 500 mg metformin fixed-dose-combination (FDC) tablet
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/31 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
6.2%
2/32 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
|
Nervous system disorders
Headache
|
16.1%
5/31 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
15.6%
5/32 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.2%
1/31 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
6.2%
2/32 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
|
Gastrointestinal disorders
Nausea
|
6.5%
2/31 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
6.2%
2/32 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
|
Gastrointestinal disorders
Vomiting
|
6.5%
2/31 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
0.00%
0/32 • First treatment with study drug until End-of-Study (which was within 4 to 14 days after last study drug administration), i.e., 39 to 49 days after first treatment with study drug.
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER