Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2013-005143-85 | EudraCT Number | EudraCT |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
The purpose of this trial is to demonstrate bioequivalence of a newly developed fixed dose combination (FDC) tablet containing linagliptin and metformin extended release compared to the free combination of linagliptin and metformin extended release.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FDC first, fasted | Experimental | Linagliptin/Metformin ER FDC followed by single tablets of linagliptin and metformin ER, fasted condition |
|
| Single tablets first, fasted | Experimental | single tablets of linagliptin and metformin ER followed by Linagliptin/Metformin ER FDC, fasted condition |
|
| FDC first, fed | Experimental | Linagliptin/Metformin ER FDC followed by single tablets of linagliptin and metformin ER, fed condition |
|
| Single tablets first, fed | Experimental | single tablets of linagliptin and metformin ER followed by Linagliptin/Metformin ER FDC, fed condition |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Linagliptin | Drug | 1 x Linagliptin tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) | AUC 0-72 (area under the concentration-time curve of the Linagliptin in plasma from 0 to 72 hours) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
| Maximum Measured Concentration of Linagliptin in Plasma (Cmax) | Cmax (maximum measured concentration of Linagliptin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after 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) | AUC 0-tz (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
| Cmax of Metformin in Plasma | Cmax (maximum measured concentration of the Metformin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Linagliptin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. |
Not provided
Inclusion criteria:
- Healthy male or female subjects
Exclusion criteria:
- Any relevant deviation from healthy condition
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1288.10.1 Boehringer Ingelheim Investigational Site | Ingelheim | Germany |
Not provided
The study is conducted in two parts:
Part 1 of the study was conducted in fasting conditions. Part 2 of the study was conducted in fed conditions.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | FDC 1500 Fasted / L+M 1500 Fasted | Linagliptin+ Metformin extended release (XR) (FDC)-(T fasted): 5 mg linagliptin/1500 mg metformin XR (given as 2*2.5mg linagliptin/750mg metformin XR FDC tablets) followed by Linagliptin+ Metformin-(R fasted): 5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) orally with 240 mL of water after an overnight fast of at least 10 h. Where, L+M = Linagliptin 5mg+Metformin XR 1500mg |
| FG001 | L+M 1500 Fasted / FDC 1500 Fasted | Linagliptin+ Metformin-(R fasted): 5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) followed by Linagliptin+ Metformin XR (FDC)-(T fasted): 5 mg linagliptin/1500 mg metformin XR orally with 240 mL of water after an overnight fast of at least 10 h. Where, L+M = Linagliptin 5mg+Metformin XR 1500mg |
| FG002 | FDC 1500 Fed / L+M 1500 Fed | Linagliptin+ Metformin XR (FDC)-(T fasted): 5 mg linagliptin/1500 mg metformin XR (given as 2*2.5mg linagliptin/750mg metformin XR FDC tablets) followed by Linagliptin+ Metformin-(R fasted): 5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) orally with 240 mL of water after after a high-fat, high-calorie meal. Where, L+M = Linagliptin 5mg+Metformin XR 1500mg |
| FG003 | L+M 1500 Fed / FDC 1500 Fed | Linagliptin+ Metformin-(R fasted): 5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) followed by Linagliptin+ Metformin XR (FDC)-(T fasted): 5 mg linagliptin/1500 mg metformin XR orally with 240 mL of water after a high-fat, high-calorie meal. Where, L+M = Linagliptin 5mg+Metformin XR 1500mg |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period-1 (4 Days) |
| |||||||||||||
| Washout Period (35 Days) |
| |||||||||||||
| Treatment Period-2 (4 Days) |
|
The treated set (TS) included all subjects who had taken at least 1 dose of study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | FDC 1500 Fasted or L+M 1500 Fasted | The subjects in Part 1 were randomly allocated to 1 of the 2 treatment sequences T fasted_R fasted or R fasted_T fasted. FDC 1500 fasted (T fasted): 5 mg linagliptin/1500 mg metformin XR (given as 2*2.5mg linagliptin/750mg metformin XR FDC tablets) orally with 240 mL of water after an overnight fast of at least 10 h. L+M 1500 fasted (R fasted): 5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) orally with 240 mL of water after an overnight fast of at least 10 h. Where, L+M = Linagliptin 5mg+Metformin XR 1500mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) | AUC 0-72 (area under the concentration-time curve of the Linagliptin in plasma from 0 to 72 hours) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | PKS1500 Fast and PKS1500 Fed, included all treated subjects in Part 1 and Part 2, who provided at least 1 observation for at least 1 primary endpoint, without important protocol violations regarding the statistical evaluation of pharmacokinetic endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
|
From the first drug administration for at least 7 days after the last drug administration, up to 43 days.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | L+M 1500 Fasted | 5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) orally with 240 mL of water after an overnight fast of at least 10 h. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
Not provided
| ID | Term |
|---|---|
| D000069476 | Linagliptin |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Linagliptin/Metformin ER FDC | Drug | 2 x Linagliptin/Metformin ER FDC tablet |
|
| Metformin ER | Drug | 3 x Metformin ER tablets |
|
| 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
| AUC0-inf of Metformin in Plasma | AUC0-inf(area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Metformin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | FDC 1500 Fed or L+M 1500 Fed | The subjects in Part 2 were randomly allocated to 1 of the 2 treatment sequences T fed_R fed or R fed_T fed. FDC 1500 fed (T fed): 5 mg linagliptin/1500 mg metformin XR (given as 2*2.5mg linagliptin/750mg metformin XR FDC tablets) orally with 240 mL of water after after a high-fat, high-calorie meal. L+M 1500 fed (R fed): 5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) orally with 240 mL of water after a high-fat, high-calorie meal. Where, L+M = Linagliptin 5mg+Metformin XR 1500mg |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) orally with 240 mL of water after an overnight fast of at least 10 h.
| OG001 | FDC 1500 Fasted | 5 mg linagliptin/1500 mg metformin XR (given as 2*2.5mg linagliptin/750mg metformin XR FDC tablets) orally with 240 mL of water after an overnight fast of at least 10 h. |
| OG002 | L+M 1500 Fed | 5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) orally with 240 mL of water after a high-fat, high-calorie meal. |
| OG003 | FDC 1500 Fed | 5 mg linagliptin/1500 mg metformin XR (given as 2*2.5mg linagliptin/750mg metformin XR FDC tablets) orally with 240 mL of water after a high-fat, high-calorie meal. |
|
|
|
| Primary | Maximum Measured Concentration of Linagliptin in Plasma (Cmax) | Cmax (maximum measured concentration of Linagliptin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | PKS 1500 fast and PKS 1500 fed, included all treated subjects in Part 1 and Part 2, respectively, who provided at least 1 observation for at least 1 primary endpoint, without important protocol violations regarding the statistical evaluation of pharmacokinetic endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
|
|
|
|
| Primary | Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | AUC 0-tz (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | PKS 1500 fast and PKS 1500 fed, included all treated subjects in Part 1 and Part 2, respectively, who provided at least 1 observation for at least 1 primary endpoint, without important protocol violations regarding the statistical evaluation of pharmacokinetic endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
|
|
|
|
| Primary | Cmax of Metformin in Plasma | Cmax (maximum measured concentration of the Metformin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | PKS 1500 fast and PKS 1500 fed, included all treated subjects in Part 1 and Part 2, respectively, who provided at least 1 observation for at least 1 primary endpoint, without important protocol violations regarding the statistical evaluation of pharmacokinetic endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
|
|
|
|
| Secondary | Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Linagliptin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | PKS 1500 fast and PKS 1500 fed, included all treated subjects in Part 1 and Part 2, respectively, who provided at least 1 observation for at least 1 primary endpoint, without important protocol violations regarding the statistical evaluation of pharmacokinetic endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
|
|
|
|
| Secondary | AUC0-inf of Metformin in Plasma | AUC0-inf(area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Metformin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | PKS 1500 fast and PKS 1500 fed, included all treated subjects in Part 1 and Part 2, respectively, who provided at least 1 observation for at least 1 primary endpoint, without important protocol violations regarding the statistical evaluation of pharmacokinetic endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |
|
|
|
|
| 0 |
| 56 |
| 15 |
| 56 |
| EG001 | FDC 1500 Fasted | 5 mg linagliptin/1500 mg metformin XR (given as 2*2.5mg linagliptin/750mg metformin XR FDC tablets) orally with 240 mL of water after an overnight fast of at least 10 h. | 0 | 54 | 22 | 54 |
| EG002 | L+M 1500 Fed | 5 mg linagliptin and 1500 mg metformin XR (given as 1 tablet 5 mg linagliptin and 3 tablets 500 mg metformin XR) orally with 240 mL of water after a high-fat, high-calorie meal. | 0 | 16 | 8 | 16 |
| EG003 | FDC 1500 Fed | 5 mg linagliptin/1500 mg metformin XR (given as 2*2.5mg linagliptin/750mg metformin XR FDC tablets) orally with 240 mL of water after a high-fat, high-calorie meal. | 0 | 16 | 3 | 16 |
| Abdominal pain | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D011799 | Quinazolines |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| ANOVA | ANOVA on the logarithmic scale including effects for 'sequence', 'subjects within sequences', 'period', and 'treatment'. | 0.0040 | Adjusted Geometric Mean ratio | 106.71 | Standard Error of the Mean | 1.051 | 2-Sided | 90 | 97.614 | 116.658 | Ratio of (FDC 1500 fed/ L+M 1500 fed) | Yes | Non-Inferiority or Equivalence | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratios of the geometric means (FDC/free combination) using an acceptance range of 80.00 to 125.00%. |
| ANOVA | ANOVA on the logarithmic scale including effects for 'sequence', 'subjects within sequences', 'period', and 'treatment'. | 0.0002 | Adjusted Geometric Mean ratio | 96.36 | Standard Error of the Mean | 1.04 | 2-Sided | 90 | 89.96 | 103.22 | Ratio of (FDC 1500 fed/ L+M 1500 fed) | Yes | Non-Inferiority or Equivalence | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratios of the geometric means (FDC/free combination) using an acceptance range of 80.00 to 125.00%. |
| ANOVA | ANOVA on the logarithmic scale including effects for 'sequence', 'subjects within sequences', 'period', and 'treatment'. | 0.0018 | Adjusted Geometric Means ratio | 113.91 | Standard Error of the Mean | 1.027 | 2-Sided | 90 | 108.749 | 119.318 | Ratio of (FDC 1500 fed/ L+M 1500 fed) | Yes | Non-Inferiority or Equivalence | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratios of the geometric means (FDC/free combination) using an acceptance range of 80.00 to 125.00%. |
| ANOVA | ANOVA on the logarithmic scale including effects for 'sequence', 'subjects within sequences', 'period', and 'treatment'. | 0.0002 | Adjusted Geometric Means ratio | 106.33 | Standard Error of the Mean | 1.034 | 2-Sided | 90 | 100.268 | 112.763 | Ratio of (FDC 1500 fed/ L+M 1500 fed) | Yes | Non-Inferiority or Equivalence | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratios of the geometric means (FDC/free combination) using an acceptance range of 80.00 to 125.00%. |
| ANOVA | ANOVA on the logarithmic scale including effects for 'sequence', 'subjects within sequences', 'period', and 'treatment'. | 0.0001 | Adjusted Geometric Means ratio | 96.79 | Standard Error of the Mean | 1.04 | 2-Sided | 90 | 90.33 | 103.70 | Ratio of (FDC 1500 fed/ L+M 1500 fed) | Yes | Non-Inferiority or Equivalence | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratios of the geometric means (FDC/free combination) using an acceptance range of 80.00 to 125.00%. |