Trial Outcomes & Findings for Pharmacokinetics of Fixed Dose Combination (FDC) Tablets of Linagliptin /Metformin (NCT NCT01540487)

NCT ID: NCT01540487

Last Updated: 2013-08-06

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

48 participants

Primary outcome timeframe

1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

Results posted on

2013-08-06

Participant Flow

Participant milestones

Participant milestones
Measure
Lina 2.5mg, Metformin 850mg
All patients receiving Linagliptin 2.5mg and Metformin 850mg.
Lina 2.5mg, Metformin 500mg
All patients receiving Linagliptin 2.5mg and Metformin 500mg.
Overall Study
STARTED
24
24
Overall Study
COMPLETED
23
24
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Lina 2.5mg, Metformin 850mg
All patients receiving Linagliptin 2.5mg and Metformin 850mg.
Lina 2.5mg, Metformin 500mg
All patients receiving Linagliptin 2.5mg and Metformin 500mg.
Overall Study
Protocol Violation
1
0

Baseline Characteristics

Pharmacokinetics of Fixed Dose Combination (FDC) Tablets of Linagliptin /Metformin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Lina 2.5mg, Metformin 850mg
n=24 Participants
All patients receiving Linagliptin 2.5mg and Metformin 850mg.
Lina 2.5mg, Metformin 500mg
n=24 Participants
All patients receiving Linagliptin 2.5mg and Metformin 500mg.
Total
n=48 Participants
Total of all reporting groups
Age Continuous
27.8 years
STANDARD_DEVIATION 4.4 • n=5 Participants
28.6 years
STANDARD_DEVIATION 4.8 • n=7 Participants
28.2 years
STANDARD_DEVIATION 4.6 • n=5 Participants
Sex: Female, Male
Female
12 Participants
n=5 Participants
12 Participants
n=7 Participants
24 Participants
n=5 Participants
Sex: Female, Male
Male
12 Participants
n=5 Participants
12 Participants
n=7 Participants
24 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

Population: Treated Set.

Outcome measures

Outcome measures
Measure
Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet
n=23 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as single tablets.
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as single tablets.
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)
248 nmol*h/L
Geometric Coefficient of Variation 14.5
251 nmol*h/L
Geometric Coefficient of Variation 15.3
266 nmol*h/L
Geometric Coefficient of Variation 22.1
264 nmol*h/L
Geometric Coefficient of Variation 23.8

PRIMARY outcome

Timeframe: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

Population: Treated Set.

Outcome measures

Outcome measures
Measure
Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet
n=23 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as single tablets.
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as single tablets.
Maximum Measured Concentration (Cmax) of Linagliptin.
6.90 nmol/L
Geometric Coefficient of Variation 23.1
6.81 nmol/L
Geometric Coefficient of Variation 18.2
7.54 nmol/L
Geometric Coefficient of Variation 35.4
6.77 nmol/L
Geometric Coefficient of Variation 25.9

PRIMARY outcome

Timeframe: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

Outcome measures

Outcome measures
Measure
Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet
n=23 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as single tablets.
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as single tablets.
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval 0 to the Last Quantifiable Concentration (AUC0-tz)
11700 ng*h/mL
Geometric Coefficient of Variation 27.9
12100 ng*h/mL
Geometric Coefficient of Variation 23.2
8240 ng*h/mL
Geometric Coefficient of Variation 20.8
8010 ng*h/mL
Geometric Coefficient of Variation 21.3

PRIMARY outcome

Timeframe: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

Outcome measures

Outcome measures
Measure
Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet
n=23 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as single tablets.
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as single tablets.
Maximum Measured Concentration (Cmax) of Metformin
1680 ng/mL
Geometric Coefficient of Variation 34.8
1780 ng/mL
Geometric Coefficient of Variation 26.0
1220 ng/mL
Geometric Coefficient of Variation 29.1
1190 ng/mL
Geometric Coefficient of Variation 27.2

SECONDARY outcome

Timeframe: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

AUC0-infinity is based on predicted last concentration values.

Outcome measures

Outcome measures
Measure
Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet
n=23 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as single tablets.
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as single tablets.
Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) for Linagliptin
471 nmol*h/L
Geometric Coefficient of Variation 29.8
433 nmol*h/L
Geometric Coefficient of Variation 22.2
483 nmol*h/L
Geometric Coefficient of Variation 32.5
541 nmol*h/L
Geometric Coefficient of Variation 36.4

SECONDARY outcome

Timeframe: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

AUC0-infinity is based on predicted last concentration values.

Outcome measures

Outcome measures
Measure
Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet
n=23 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as single tablets.
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as single tablets.
AUC(0-infinity) for Metformin
12200 ng*h/mL
Geometric Coefficient of Variation 25.8
12500 ng*h/mL
Geometric Coefficient of Variation 23.0
8440 ng*h/mL
Geometric Coefficient of Variation 19.3
8210 ng*h/mL
Geometric Coefficient of Variation 20.3

SECONDARY outcome

Timeframe: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

Population: Treated Set

Outcome measures

Outcome measures
Measure
Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet
n=23 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as single tablets.
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets
n=24 Participants
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as single tablets.
AUC0-tz for Linagliptin
248 nmol*h/L
Geometric Coefficient of Variation 14.5
251 nmol*h/L
Geometric Coefficient of Variation 15.3
266 nmol*h/L
Geometric Coefficient of Variation 22.1
264 nmol*h/L
Geometric Coefficient of Variation 23.8

Adverse Events

Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet
n=23 participants at risk
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets
n=24 participants at risk
Patients receiving 2.5 mg Linagliptin and 850 mg Metformin as single tablets.
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet
n=24 participants at risk
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as a fixed dose combination (FDC) tablet.
Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets
n=24 participants at risk
Patients receiving 2.5 mg Linagliptin and 500 mg Metformin as single tablets.
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
0.00%
0/23 • First treatment with study drug until End-of-Study (which was 7 to 14 days after study drug treatment in Visit 3), i.e. 7 weeks plus 4 to 11 days after first treatment with study drug
8.3%
2/24 • First treatment with study drug until End-of-Study (which was 7 to 14 days after study drug treatment in Visit 3), i.e. 7 weeks plus 4 to 11 days after first treatment with study drug
0.00%
0/24 • First treatment with study drug until End-of-Study (which was 7 to 14 days after study drug treatment in Visit 3), i.e. 7 weeks plus 4 to 11 days after first treatment with study drug
8.3%
2/24 • First treatment with study drug until End-of-Study (which was 7 to 14 days after study drug treatment in Visit 3), i.e. 7 weeks plus 4 to 11 days after first treatment with study drug

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Results disclosure agreements

  • Principal investigator is a sponsor employee Other - 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