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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-005142-11 | EudraCT Number | EudraCT |
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| 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, both under fed and fasted conditions.
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| 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 |
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| 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/Metformin ER FDC | Drug | 1x Linagliptin/Metformin FDC 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 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-t (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. |
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Inclusion criteria:
- Healthy male or female subjects
Exclusion criteria:
- Any relevant deviation from healthy condition
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1288.9.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | FDC 1000 Fast/ L+M 1000 Fast | Linagliptin/Metformin Extended Release (XR) Fixed dose combination (given as 1 FDC tablet) followed by single tablets of linagliptin and metformin XR (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR), oral with 240 mL of water after an overnight fast of at least 10 h. Where, L+M = Linagliptin 5mg+Metformin 1000mg |
| FG001 | L+M1000 Fast/ FDC1000 Fast | Single tablets of linagliptin and metformin Extended Release (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR) followed by Linagliptin/Metformin XR Fixed Dose Combination (given as 1 FDC tablet), oral with 240 mL of water after an overnight fast of at least 10 h. Where, L+M = Linagliptin 5mg+Metformin 1000mg |
| FG002 | FDC1000 Fed/L+M1000 Fed | Linagliptin/Metformin XR FDC (given as 1 FDC tablet) followed by single tablets of linagliptin and metformin XR (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR), oral with 240 mL of water after a high-fat, high-calorie meal. Where, L+M = Linagliptin 5mg+Metformin 1000mg |
| FG003 | L+M1000 Fed/ FDC1000 Fed | Single tablets of linagliptin and metformin XR (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR) followed by Linagliptin/Metformin XR FDC (given as 1 FDC tablet), oral with 240 mL of water after a high-fat, high-calorie meal. Where, L+M = Linagliptin 5mg+Metformin 1000mg |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (4 Days) |
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| Washout Period 1 (35 Days) |
| |||||||||||||
| Treatment Period 2 (4 Days) |
|
Treated set: All randomised subjects who received 1 dose of trial medication were included in the treated set.
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| ID | Title | Description |
|---|---|---|
| BG000 | FDC 1000 Fast or L+M 1000 Fast | 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 1000 fast (T fasted): 5 mg linagliptin/1000 mg metformin XR (given as 1 FDC tablet) orally with 240 mL of water after an overnight fast of at least 10 h. L+M 1000 fast (R fasted): 5 mg linagliptin and 1000 mg metformin XR (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR) oral with 240 mL of water after an overnight fast of at least 10 h. Where, L+M = Linagliptin 5mg+Metformin 1000mg |
| 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 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. | PKS 1000 fast and PKS 1000 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 |
|
From the first drug administration for at least 7 days after the last drug administration, up to 49 days.
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| 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 1000 Fasted | 5 mg linagliptin and 1000 mg metformin XR (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR) oral with 240 mL of water after an overnight fast of at least 10 h. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acetabulum fracture | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D000069476 | Linagliptin |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Linagliptin | Drug | 1x Linagliptin tablet |
|
| Metformin ER | Drug | 2x 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 |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG001 | FDC 1000 Fed or L+M 1000 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 1000 fed (T fed): 5 mg linagliptin/1000 mg metformin XR (given as 1 FDC tablet) orally with 240 mL of water after after a high-fat, high-calorie meal. L+M 1000 fed (R fed): 5 mg linagliptin and 1000 mg metformin XR (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR) oral with 240 mL of water after a high-fat, high-calorie meal. Where, L+M = Linagliptin 5mg+Metformin 1000mg |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
5 mg linagliptin and 1000 mg metformin XR (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR) oral with 240 mL of water after an overnight fast of at least 10 h.
| OG001 | FDC 1000 Fasted | 5 mg linagliptin/1000 mg metformin XR (given as 1 FDC tablet) orally with 240 mL of water after an overnight fast of at least 10 h. |
| OG002 | L+M 1000 Fed | 5 mg linagliptin and 1000 mg metformin XR (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR) oral with 240 mL of water after a high-fat, high-calorie meal. |
| OG003 | FDC 1000 Fed | 5 mg linagliptin/1000 mg metformin XR (given as 1 FDC tablet) orally with 240 mL of water after 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 1000 fast and PKS 1000 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-t (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 1000 fast and PKS 1000 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 1000 fast and PKS 1000 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 1000 fast and PKS 1000 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 1000 fast and PKS 1000 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 |
| 52 |
| 4 |
| 52 |
| EG001 | FDC 1000 Fasted | 5 mg linagliptin/1000 mg metformin XR (given as 1 FDC tablet) orally with 240 mL of water after an overnight fast of at least 10 h. | 0 | 52 | 9 | 52 |
| EG002 | L+M 1000 Fed | 5 mg linagliptin and 1000 mg metformin XR (given as 1 tablet 5 mg linagliptin and 2 tablets 500 mg metformin XR) oral with 240 mL of water after a high-fat, high-calorie meal. | 2 | 15 | 4 | 15 |
| EG003 | FDC 1000 Fed | 5 mg linagliptin/1000 mg metformin XR (given as 1 FDC tablet) orally with 240 mL of water after after a high-fat, high-calorie meal. | 0 | 14 | 4 | 14 |
| Bone contusion | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Concussion | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Muscle contusion | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
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| 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'. | <0.0001 | Adjusted Geometric Means ratio | 98.24 | Standard Error of the Mean | 1.024 | 2-Sided | 90 | 94.067 | 102.597 | Ratio of (FDC 1000_fed / L+M 1000 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 | 96.95 | Standard Error of the Mean | 1.03 | 2-Sided | 90 | 92.24 | 101.89 | Ratio of (FDC 1000_fed / L+M 1000 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 | 98.97 | Standard Error of the Mean | 1.023 | 2-Sided | 90 | 94.950 | 103.160 | Ratio of (FDC 1000_fed / L+M 1000 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'. | 0.0778 | Adjusted Geometric Means ratio | 97.36 | Standard Error of the Mean | 1.132 | 2-Sided | 90 | 77.082 | 122.963 | Ratio of (FDC 1000_fed / L+M 1000 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 | 98.18 | Standard Error of the Mean | 1.03 | 2-Sided | 90 | 93.34 | 103.27 | Ratio of (FDC 1000_fed / L+M 1000 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%. |