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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-019291-75 | EudraCT Number | EudraCT |
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The objective of the current study is to investigate the relative bioavailability of two different batches of a 2.5 mg linagliptin / 1000 mg metformin fixed dose combination tablet (FDC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Linagliptin/Metformin (standard batch) | Experimental | Fixed dose combination tablet |
|
| Linagliptin/Metformin (side batch) | Experimental | Fixed dose combination tablet |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Linagliptin/Metformin (standard batch) | Drug | Fixed dose combination tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Linagliptin: Maximum Measured Concentration (Cmax) | Geometric mean of Cmax of Linagliptin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72) | Geometric mean of AUC0-72 of Linagliptin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: Cmax | Geometric Mean of Cmax of Metformin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: AUC0-tz | Geometric Mean of AUC0-tz of Metformin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Linagliptin: AUC0-infinity | Geometric mean of AUC0-infinity of Linagliptin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation |
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Inclusion criteria:
Exclusion criteria:
Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
Any evidence of a clinically relevant concomitant disease
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Surgery of the gastrointestinal tract (except appendectomy)
Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
History of relevant orthostatic hypotension, fainting spells or blackouts
Chronic or relevant acute infections
History of relevant allergy or hypersensitivity (including allergy to drug or its excipients)
Intake of drugs within one month or less than 10 half-lives of the respective drug prior to first study drug administration
Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
Smoker (more than 10 cigarettes or 3 cigars 3 pipes daily)
Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in males)
Drug abuse
Blood donation (more than 100 mL within four weeks prior to day 1 of visit 2)
Any laboratory value outside the reference range that is of clinical relevance
Inability to comply with dietary regimen of trial site
For female subjects of childbearing potential only:
Positive pregnancy test, pregnancy or planning to become pregnant 1 month before study or within 2 months after study completion
No adequate contraception 1 month before study and until 2 month after study completion, e.g. not any of the following: implants, injectables, combined hormonal contraceptives, hormonal IUD (intrauterine device), sexual abstinence for at least 1 month prior to first study drug administration, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to use an additional barrier method (e.g. condom).
Lactation
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1288.6.1 Boehringer Ingelheim Investigational Site | Ingelheim | Germany |
This was an open-label, single-dose, randomised, 2-way crossover trial. Subjects were equally randomised to one of two sequences, and in general terms, AB or BA. Hence, 20 subjects were in group AB and 20 in group BA. All 40 subjects received A and B. The numbers presented in the milestones are overall, which is consistent with the trial report.
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard Batch Then Side Batch | Linagliptin/metformin FDC tablet from standard batch, then Linagliptin/metformin FDC tablet from side batch |
| FG001 | Side Batch Then Standard Batch | Linagliptin/metformin FDC tablet from side batch, then Linagliptin/metformin FDC tablet from standard batch |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Washout (35 Days) |
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| Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | Treatment with standard batch and side batch |
| 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 | Linagliptin: Maximum Measured Concentration (Cmax) | Geometric mean of Cmax of Linagliptin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
4 days (period 1) + 4 days (treatment period 2)
Two identical treatment periods with an interval of at least 35 days between drug administrations.
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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 | Standard Batch | standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 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/Metformin (side batch) | Drug | Fixed dose combination tablet |
|
Geometric Mean of percentage of AUCtz-∞ of linagliptin, where percentage is the unit of measurement.
| Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax) | Median of the t_max of linagliptin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Linagliptin: λz (Terminal Elimination Rate Constant in Plasma) | Geometric mean of the λ_z of linagliptin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| t1/2 (Terminal Half-life of the Analyte in Plasma) | Geometric mean of the t1/2 of linagliptin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) | Geometric mean of the MRTpo of linagliptin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F) | Geometric mean of the CL/F of linagliptin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F) | Geometric mean of the Vz/F of linagliptin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: AUC0-infinity | Geometric Mean of AUC0-infinity of Metformin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation | Geometric Mean of the percentage of AUCtz-infinity of Metformin, where percentage is the unit of measurement. | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: Tmax | Median of tmax of metformin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: λz (Terminal Elimination Rate Constant in Plasma) | Geometric mean of λz of metformin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma) | Geometric mean of t1/2 of metformin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) | Geometric mean of MRTpo of metformin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: CL/F | Geometric mean of CL/F of metformin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Metformin: Vz/F | Geometric mean of Vz/F of metformin | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
| Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | 12-lead-Electrocardiogram (ECG), vital sign (blood pressure and pulse rate), physical finding and laboratory abnormalities | Day 1 to 4 for period 1, and day 36 to 39 for period 2 |
| Participants With Treatment Emergent Adverse Events | Number of patients with treatment emergent AEs | Day 1 to 4 for period 1, and day 36 to 39 for period 2 |
| Participants Who Discontinued the Trial Because of an Adverse Event | Number of participants who discontinued the trial because of an adverse event | Day 1 to 4 for period 1, and day 36 to 39 for period 2 |
| Assessment of Tolerability by the Investigator | Qualitative variable assessing the tolerability by the investigator | Day 1 to 4 for period 1, and day 36 to 39 for period 2 |
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| NOT COMPLETED |
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| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
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| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|
| Primary | Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72) | Geometric mean of AUC0-72 of Linagliptin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*hr/L | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
|
| Secondary | Linagliptin: AUC0-infinity | Geometric mean of AUC0-infinity of Linagliptin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*hr/L | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
|
| Secondary | Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation | Geometric Mean of percentage of AUCtz-∞ of linagliptin, where percentage is the unit of measurement. | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax) | Median of the t_max of linagliptin | Treated Set | Posted | Median | Full Range | hr | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Linagliptin: λz (Terminal Elimination Rate Constant in Plasma) | Geometric mean of the λ_z of linagliptin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/hr | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | t1/2 (Terminal Half-life of the Analyte in Plasma) | Geometric mean of the t1/2 of linagliptin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) | Geometric mean of the MRTpo of linagliptin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F) | Geometric mean of the CL/F of linagliptin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F) | Geometric mean of the Vz/F of linagliptin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Primary | Metformin: Cmax | Geometric Mean of Cmax of Metformin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
|
| Primary | Metformin: AUC0-tz | Geometric Mean of AUC0-tz of Metformin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
|
| Secondary | Metformin: AUC0-infinity | Geometric Mean of AUC0-infinity of Metformin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
|
| Secondary | Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation | Geometric Mean of the percentage of AUCtz-infinity of Metformin, where percentage is the unit of measurement. | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Metformin: Tmax | Median of tmax of metformin | Treated Set | Posted | Median | Full Range | hr | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Metformin: λz (Terminal Elimination Rate Constant in Plasma) | Geometric mean of λz of metformin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/hr | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma) | Geometric mean of t1/2 of metformin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) | Geometric mean of MRTpo of metformin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Metformin: CL/F | Geometric mean of CL/F of metformin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Metformin: Vz/F | Geometric mean of Vz/F of metformin | Treated Set | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 |
|
|
|
| Secondary | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | 12-lead-Electrocardiogram (ECG), vital sign (blood pressure and pulse rate), physical finding and laboratory abnormalities | Treated Set | Posted | Number | Participants | Day 1 to 4 for period 1, and day 36 to 39 for period 2 |
|
|
|
| Secondary | Participants With Treatment Emergent Adverse Events | Number of patients with treatment emergent AEs | Treated Set | Posted | Number | Participants | Day 1 to 4 for period 1, and day 36 to 39 for period 2 |
|
|
|
| Secondary | Participants Who Discontinued the Trial Because of an Adverse Event | Number of participants who discontinued the trial because of an adverse event | Treated Set | Posted | Number | Participants | Day 1 to 4 for period 1, and day 36 to 39 for period 2 |
|
|
|
| Secondary | Assessment of Tolerability by the Investigator | Qualitative variable assessing the tolerability by the investigator | Treated Set | Posted | Number | Participants | Day 1 to 4 for period 1, and day 36 to 39 for period 2 |
|
|
|
| 0 |
| 40 |
| 7 |
| 40 |
| EG001 | Side Batch | side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC | 0 | 40 | 11 | 40 |
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.
| D011799 | Quinazolines |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| ECG abnormalities |
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| Laboratory finding abnormalities |
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| Vomiting |
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| Fatigue |
|