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The data from this study will be used to compare the kinetic profile of metformin 500mg in linagliptin/metformin fixed dose combination tablet versus Canadian metformin reference product administered concomitantly with linagliptin 2.5 mg tablet.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Linagliptin/Metformin medium dosecombo | Experimental | patient to receive a single medium dose combination tablet containing Linagliptin and Metformin once daily |
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| Linagliptin plus Metformin medium dose | Active Comparator | patient to receive two individual tablets: Linagliptin and Metformin (medium dose) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin Single Tablet | Drug | Metformin medium doseTablet |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | Maximum measured concentration of metformin in plasma, per period. | Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period |
| Area Under the Curve 0 to Last Measurable Value (AUC0-t) | AUC0-t is the area under the concentration versus time curve of metformin in plasma, from time zero (0) to the time of the last measurable analyte concentration (t), as calculated by the linear trapezoidal method. | Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve 0 to Inf (AUC0-inf) | AUC0-inf is the area under the concentration versus time curve of metformin in plasma from time zero extrapolated to infinity. | Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period |
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Inclusion criteria:
1. Healthy male and female subjects.
Exclusion criteria:
1. Any relevant deviation from healthy conditions.
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1288.19.1 Boehringer Ingelheim Investigational Site | Toronto | Ontario | Canada |
This is a 2 period, 2 sequence, 2 treatment crossover. Subjects were randomized to one of the two sequences AB or BA. The duration of washout was at least 35 days between dosing.
18 subjects were enrolled in the original study (June 2011 to July 2011) and 40 in the add-on study (November 2011 to December 2011) which was an option provided by protocol to increase the subject number. As no significant STUDY and STUDY-by-TREATMENT effect was revealed in analysis of pooled data, final analysis was performed on pooled data.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lina/Met 2.5mg/500mg Then Lina 2.5mg Plus Met 500mg | Combination tablet Linagliptin (Lina) /Metformin (Met) 2.5mg/500mg followed by single tablets Linagliptin 2.5mg plus Metformin 500mg |
| FG001 | Lina 2.5mg Plus Met 500mg Then Lina/Met 2.5mg/500mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Linagliptin/Metformin Combo |
| Drug |
Fixed dose combination |
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| Linagliptin Single Tablet | Drug | Linagliptin Single medium dose Tablet |
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Single tablets Linagliptin 2.5mg plus Metformin 500mg followed by combination tablet Linagliptin/Metformin 2.5mg/500mg |
| COMPLETED |
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| NOT COMPLETED |
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| Washout Period (at Least 35 Days) |
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| Period 2 |
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Dosed participants from combined studies
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | Total number of subjects randomised and treated in the study. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Maximum Plasma Concentration (Cmax) | Maximum measured concentration of metformin in plasma, per period. | All subjects having all samples in all periods and subjects who missed samples that may not affect the estimation of pharmacokinetic parameters in any period. | Posted | Mean | Standard Deviation | ng/ml | Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period |
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| Primary | Area Under the Curve 0 to Last Measurable Value (AUC0-t) | AUC0-t is the area under the concentration versus time curve of metformin in plasma, from time zero (0) to the time of the last measurable analyte concentration (t), as calculated by the linear trapezoidal method. | All subjects having all samples in all periods and subjects who missed samples that may not affect the estimation of pharmacokinetic parameters in any period | Posted | Mean | Standard Deviation | ng*h/ml | Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period |
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| Secondary | Area Under the Curve 0 to Inf (AUC0-inf) | AUC0-inf is the area under the concentration versus time curve of metformin in plasma from time zero extrapolated to infinity. | All subjects having all samples in all periods and subjects who missed samples that may not affect the estimation of pharmacokinetic parameters in any period | Posted | Mean | Standard Deviation | ng*h/ml | Prior to drug administration and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 30, and 36 hours post dose in each treatment period |
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Period 1 (36 hours)+ Washout (35 days) +Period 2 (36 hours)
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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 | Lina/Met 2.5mg/500mg | Combination tablet | 0 | 52 | 17 | 52 | ||
| EG001 | Lina 2.5mg Plus Met 500mg | Single tablets | 0 | 50 | 21 | 50 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000069476 | Linagliptin |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D011799 | Quinazolines |
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Bioequivalence |
| ANOVA was applied to log-transformed Cmax and included study, subject-within-study, period-within-study, treatment and study-by-treatment interaction. Results were potency corrected (GMR multiplied by the quotient of drug potency (DP) of Met in single tablet and DP of Met in combination tablet). | GMR, potency corrected (percent) | 122 | 2-Sided | 90 | 114 | 130 | Lina/Met 2.5mg/500mg vs. Lina 2.5mg plus Met 500mg. | Yes | Non-Inferiority or Equivalence | Bioequivalence |
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