Trial Outcomes & Findings for Bioequivalence of a Fixed Dose Combination Tablet Linagliptin/Pioglitazone Compared With Its Mono-components (NCT NCT01276327)
NCT ID: NCT01276327
Last Updated: 2014-06-09
Results Overview
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours
COMPLETED
PHASE1
64 participants
0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)
2014-06-09
Participant Flow
Participant milestones
| Measure |
Sequence TRTR
Subjects received 2 single doses of the test treatment (T; Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg) and 2 single doses of the reference treatment (R; Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet) in the sequence of TRTR.
|
Sequence RTRT
Subjects received 2 single doses of the test treatment (T; Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg) and 2 single doses of the reference treatment (R; Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet) in the sequence of RTRT.
|
|---|---|---|
|
Overall Study
STARTED
|
32
|
32
|
|
Overall Study
COMPLETED
|
30
|
29
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Sequence TRTR
Subjects received 2 single doses of the test treatment (T; Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg) and 2 single doses of the reference treatment (R; Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet) in the sequence of TRTR.
|
Sequence RTRT
Subjects received 2 single doses of the test treatment (T; Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg) and 2 single doses of the reference treatment (R; Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet) in the sequence of RTRT.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Bioequivalence of a Fixed Dose Combination Tablet Linagliptin/Pioglitazone Compared With Its Mono-components
Baseline characteristics by cohort
| Measure |
Sequence TRTR
n=32 Participants
Subjects received 2 single doses of the test treatment (T; Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg) and 2 single doses of the reference treatment (R; Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet) in the sequence of TRTR.
|
Sequence RTRT
n=32 Participants
Subjects received 2 single doses of the test treatment (T; Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg) and 2 single doses of the reference treatment (R; Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet) in the sequence of RTRT.
|
Total
n=64 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.8 years
STANDARD_DEVIATION 8.8 • n=99 Participants
|
38.0 years
STANDARD_DEVIATION 9.3 • n=107 Participants
|
37.9 years
STANDARD_DEVIATION 9.0 • n=206 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours
Outcome measures
| Measure |
FDC L5P30 (Test)
n=62 Participants
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 Participants
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
AUC0-72 of Linagliptin
|
278 nmol*h/L
Geometric Coefficient of Variation 20.6
|
279 nmol*h/L
Geometric Coefficient of Variation 20.6
|
PRIMARY outcome
Timeframe: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.
Maximum measured concentration of the analyte in plasma was measured. Adjusted by-treatment geometric mean and CV were reported.
Outcome measures
| Measure |
FDC L5P30 (Test)
n=62 Participants
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 Participants
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
Cmax of Linagliptin
|
8.65 nmol/L
Geometric Coefficient of Variation 33.3
|
9.09 nmol/L
Geometric Coefficient of Variation 31.2
|
PRIMARY outcome
Timeframe: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point
Outcome measures
| Measure |
FDC L5P30 (Test)
n=62 Participants
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 Participants
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
AUC0-tz of Pioglitazone
|
6370 ng*h/mL
Geometric Coefficient of Variation 49.3
|
8100 ng*h/mL
Geometric Coefficient of Variation 41.2
|
PRIMARY outcome
Timeframe: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.
Maximum concentration of the analyte in plasma was measured. Adjusted by-treatment geometric mean and CV were calculated.
Outcome measures
| Measure |
FDC L5P30 (Test)
n=62 Participants
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 Participants
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
Cmax of Pioglitazone
|
806 ng/mL
Geometric Coefficient of Variation 58.5
|
843 ng/mL
Geometric Coefficient of Variation 42.7
|
SECONDARY outcome
Timeframe: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point for Linagliptin
Outcome measures
| Measure |
FDC L5P30 (Test)
n=62 Participants
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 Participants
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
AUC0-tz for Linagliptin
|
278 nmol*h/L
Geometric Coefficient of Variation 20.6
|
279 nmol*h/L
Geometric Coefficient of Variation 20.6
|
SECONDARY outcome
Timeframe: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to infinity (inf) for linagliptin
Outcome measures
| Measure |
FDC L5P30 (Test)
n=62 Participants
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 Participants
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
AUC0-∞ of Linagliptin
|
455 nmol*h/L
Geometric Coefficient of Variation 27.4
|
447 nmol*h/L
Geometric Coefficient of Variation 24.5
|
SECONDARY outcome
Timeframe: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to inf for pioglitazone
Outcome measures
| Measure |
FDC L5P30 (Test)
n=62 Participants
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 Participants
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
AUC0-∞ of Pioglitazone
|
6580 ng*h/mL
Geometric Coefficient of Variation 47.5
|
8300 ng*h/mL
Geometric Coefficient of Variation 40.4
|
SECONDARY outcome
Timeframe: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.
Time from dosing to the maximum measured concentration of the analyte in plasma for Linagliptin
Outcome measures
| Measure |
FDC L5P30 (Test)
n=62 Participants
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 Participants
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
Tmax for Linagliptin
|
1.73 hours
Interval 0.667 to 6.93
|
1.50 hours
Interval 0.577 to 6.93
|
SECONDARY outcome
Timeframe: 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours)Population: PKS - The PKS included all evaluable subjects in the treated set who had no important PV relevant to the evaluation of bioequivalence and provided at least 1 evaluable observation for a pharmacokinetic endpoint in at least 1 treatment period.
Time from dosing to the maximum measured concentration of the analyte in plasma for pioglitazone
Outcome measures
| Measure |
FDC L5P30 (Test)
n=62 Participants
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 Participants
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
Tmax for Pioglitazone
|
1.00 hours
Interval 0.667 to 5.66
|
1.50 hours
Interval 0.65 to 4.9
|
Adverse Events
FDC L5P30 (Test)
L5+P30 (Ref)
Serious adverse events
| Measure |
FDC L5P30 (Test)
n=62 participants at risk
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 participants at risk
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/62 • 4 days treatment period (one day for every single dose), 35 days washout between drug administrations
Treated set included all subjects who were dispensed study medication and were documented to have taken at least 1 dose of any study drug. Drug administrations were separated by washout periods of at least 35 days.
|
1.6%
1/63 • 4 days treatment period (one day for every single dose), 35 days washout between drug administrations
Treated set included all subjects who were dispensed study medication and were documented to have taken at least 1 dose of any study drug. Drug administrations were separated by washout periods of at least 35 days.
|
Other adverse events
| Measure |
FDC L5P30 (Test)
n=62 participants at risk
Fixed-Dose-Combination-Tablet of linagliptin 5 mg and pioglitazone 30 mg, oral administration with 240 mL water after an overnight fast
|
L5+P30 (Ref)
n=63 participants at risk
Individual linagliptin 5mg tablet and pioglitazone 30 mg tablet, oral administration with 240 mL water after an overnight fast
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
8.1%
5/62 • 4 days treatment period (one day for every single dose), 35 days washout between drug administrations
Treated set included all subjects who were dispensed study medication and were documented to have taken at least 1 dose of any study drug. Drug administrations were separated by washout periods of at least 35 days.
|
4.8%
3/63 • 4 days treatment period (one day for every single dose), 35 days washout between drug administrations
Treated set included all subjects who were dispensed study medication and were documented to have taken at least 1 dose of any study drug. Drug administrations were separated by washout periods of at least 35 days.
|
|
Nervous system disorders
Headache
|
14.5%
9/62 • 4 days treatment period (one day for every single dose), 35 days washout between drug administrations
Treated set included all subjects who were dispensed study medication and were documented to have taken at least 1 dose of any study drug. Drug administrations were separated by washout periods of at least 35 days.
|
7.9%
5/63 • 4 days treatment period (one day for every single dose), 35 days washout between drug administrations
Treated set included all subjects who were dispensed study medication and were documented to have taken at least 1 dose of any study drug. Drug administrations were separated by washout periods of at least 35 days.
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER