Healthy
Conditions
Brief summary
The aim of the trial is to assess the relative bioavailability of fixed dose combination tablets of linagliptin and metformin compared to the administration of two single tablets (linagliptin and metformin ) in Chinese subjects. The availability of a fixed dose combination tablet is expected to significantly enhance patients' compliance with antidiabetic treatment., in particular with concern to the frequent polypharmacy in diabetic patients.
Interventions
DRUGlinagliptin/metformin(high dose)
patient would take fixed dose combination tablets of linagliptin /metformin (high dose) and single linagliptin and metformin (High dose) tablets single dose in random order, and each dosage will be separated in 42 days interval.
DRUGLinagliptin/metformin(low dose)
patient would take fixed dose combination tablets of linagliptin /metformin (low dose) and single linagliptin and metformin (Low dose) tablets single dose in random order, and each dosage will be separated in 42 days interval.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Healthy male and female subjects
Exclusion criteria
1\. Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72) | 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. |
| Maximum Measured Concentration (Cmax) of Linagliptin. | 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. |
| Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval 0 to the Last Quantifiable Concentration (AUC0-tz) | 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. |
| Maximum Measured Concentration (Cmax) of Metformin | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-infinity) for Metformin | 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. |
| AUC0-tz for Linagliptin | 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. | — |
| Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) for Linagliptin | 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lina 2.5mg, Metformin 850mg All patients receiving Linagliptin 2.5mg and Metformin 850mg. | 24 |
| Lina 2.5mg, Metformin 500mg All patients receiving Linagliptin 2.5mg and Metformin 500mg. | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Lina 2.5mg, Metformin 850mg | Lina 2.5mg, Metformin 500mg | Total |
|---|---|---|---|
| Age Continuous | 27.8 years STANDARD_DEVIATION 4.4 | 28.6 years STANDARD_DEVIATION 4.8 | 28.2 years STANDARD_DEVIATION 4.6 |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 2 / 24 | 0 / 24 | 2 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet | 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 |
| Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets | Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72) | 251 nmol*h/L | Geometric Coefficient of Variation 15.3 |
| Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet | Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72) | 266 nmol*h/L | Geometric Coefficient of Variation 22.1 |
| Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets | Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72) | 264 nmol*h/L | Geometric Coefficient of Variation 23.8 |
90% CI: [94.7, 104.5]ANOVA
90% CI: [95.1, 106.8]ANOVA
Primary
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval 0 to the Last Quantifiable Concentration (AUC0-tz)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet | 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 |
| Linagliptin 2.5 mg, Metformin 850 mg 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) | 12100 ng*h/mL | Geometric Coefficient of Variation 23.2 |
| Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet | Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval 0 to the Last Quantifiable Concentration (AUC0-tz) | 8240 ng*h/mL | Geometric Coefficient of Variation 20.8 |
| Linagliptin 2.5 mg, Metformin 500 mg 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) | 8010 ng*h/mL | Geometric Coefficient of Variation 21.3 |
90% CI: [90.6, 103.8]ANOVA
90% CI: [96.2, 110.1]ANOVA
Primary
Maximum Measured Concentration (Cmax) of Linagliptin.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet | Maximum Measured Concentration (Cmax) of Linagliptin. | 6.90 nmol/L | Geometric Coefficient of Variation 23.1 |
| Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets | Maximum Measured Concentration (Cmax) of Linagliptin. | 6.81 nmol/L | Geometric Coefficient of Variation 18.2 |
| Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet | Maximum Measured Concentration (Cmax) of Linagliptin. | 7.54 nmol/L | Geometric Coefficient of Variation 35.4 |
| Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets | Maximum Measured Concentration (Cmax) of Linagliptin. | 6.77 nmol/L | Geometric Coefficient of Variation 25.9 |
90% CI: [95.4, 109]ANOVA
90% CI: [100.4, 123.5]ANOVA
Primary
Maximum Measured Concentration (Cmax) of Metformin
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet | Maximum Measured Concentration (Cmax) of Metformin | 1680 ng/mL | Geometric Coefficient of Variation 34.8 |
| Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets | Maximum Measured Concentration (Cmax) of Metformin | 1780 ng/mL | Geometric Coefficient of Variation 26 |
| Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet | Maximum Measured Concentration (Cmax) of Metformin | 1220 ng/mL | Geometric Coefficient of Variation 29.1 |
| Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets | Maximum Measured Concentration (Cmax) of Metformin | 1190 ng/mL | Geometric Coefficient of Variation 27.2 |
90% CI: [85.4, 104.8]ANOVA
90% CI: [92.2, 113.9]ANOVA
Secondary
Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) for Linagliptin
AUC0-infinity is based on predicted last concentration values.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet | 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 |
| Linagliptin 2.5 mg, Metformin 850 mg 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 | 433 nmol*h/L | Geometric Coefficient of Variation 22.2 |
| Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet | Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) for Linagliptin | 483 nmol*h/L | Geometric Coefficient of Variation 32.5 |
| Linagliptin 2.5 mg, Metformin 500 mg 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 | 541 nmol*h/L | Geometric Coefficient of Variation 36.4 |
90% CI: [100.5, 120.6]ANOVA
90% CI: [80.2, 99.3]ANOVA
Secondary
AUC(0-infinity) for Metformin
AUC0-infinity is based on predicted last concentration values.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet | AUC(0-infinity) for Metformin | 12200 ng*h/mL | Geometric Coefficient of Variation 25.8 |
| Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets | AUC(0-infinity) for Metformin | 12500 ng*h/mL | Geometric Coefficient of Variation 23 |
| Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet | AUC(0-infinity) for Metformin | 8440 ng*h/mL | Geometric Coefficient of Variation 19.3 |
| Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets | AUC(0-infinity) for Metformin | 8210 ng*h/mL | Geometric Coefficient of Variation 20.3 |
90% CI: [92, 104.5]ANOVA
90% CI: [97, 109]ANOVA
Secondary
AUC0-tz for Linagliptin
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet | AUC0-tz for Linagliptin | 248 nmol*h/L | Geometric Coefficient of Variation 14.5 |
| Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets | AUC0-tz for Linagliptin | 251 nmol*h/L | Geometric Coefficient of Variation 15.3 |
| Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet | AUC0-tz for Linagliptin | 266 nmol*h/L | Geometric Coefficient of Variation 22.1 |
| Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets | AUC0-tz for Linagliptin | 264 nmol*h/L | Geometric Coefficient of Variation 23.8 |
90% CI: [94.7, 104.6]ANOVA
90% CI: [95.1, 106.8]ANOVA