Clinical trial NCT02221401: Bioequivalence of a Linagliptin / Metformin Fixed-dose Combination (FDC) Tablet Compared With Single Linagliptin and Metformin Tablets Administered Together in Healthy Volunteers
Official title: Bioequivalence of a 2.5 mg Linagliptin / 1000 mg Metformin Fixed-dose Combination Tablet Compared With Single Linagliptin 2.5 mg and Metformin 1000 mg Tablets Administered Together in Healthy Male and Female Volunteers (an Open-label, Randomised, Single Dose, Two-way Crossover, Phase I Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-20
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Study to demonstrate bioequivalence of a 2.5 mg linagliptin/1000 mg metformin fixed-dose combination (FDC) tablet compared with single tablets of linagliptin 2.5 mg and metformin 1000 mg administered together.


Eligibility criteria: Inclusion Criteria:

1. Healthy men and women according to the following criteria: based upon a complete medical history, including physical examination, vital signs (Blood pressure (BP), Pulse Rate (PR)), 12-lead ECG, clinical laboratory tests
2. Age 18 to 55 years (inclusive)
3. Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion Criteria:

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. Surgery of the gastrointestinal tract (except appendectomy)
5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
6. History of relevant orthostatic hypotension, fainting spells or blackouts
7. Chronic or relevant acute infections
8. History of relevant allergy or hypersensitivity (including allergy to drug or its excipients)
9. Intake of drugs within 1 month or less than 10 half-lives of the respective drug prior to first study drug administration
10. Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
11. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes daily)
12. Alcohol abuse (average consumption of more than 20 g/day in women and 30 g/day in men)
13. Drug abuse
14. Blood donation (more than 100 mL within 4 weeks before Day 1 of Visit 2)
15. Any laboratory value outside the reference range of clinical relevance
16. Inability to comply with dietary regimen of trial site

    For female subjects of childbearing potential only:
17. Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 2 months after study completion
18. No adequate contraception during the study and until 1 month after study completion, e.g. not any of the following: implants, injectables, combined hormonal contraceptives, hormonal 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 sterilization (including hysterectomy). Women who did not have a vasectomised partner, were not sexually abstinent or surgically sterile were asked to use an additional barrier method (e.g. condom).
19. Lactation

Primary outcomes:
measure: AUC0-72 (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 h)
timeFrame: up to 72 hours
measure: Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: up to 72 hours
measure: AUC0-∞ (area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 72 hours
Secondary outcomes:
measure: AUC0-∞ (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 72 hours
measure: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
timeFrame: up to 72 hours
measure: %AUCtz-∞ (percentage of AUCtz-∞ obtained by extrapolation)
timeFrame: up to 72 hours
measure: AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)
timeFrame: up to 72 hours
measure: tmax (time from dosing until maximum concentration of the analyte in plasma)
timeFrame: up to 72 hours
measure: λz (terminal elimination rate constant in plasma)
timeFrame: up to 72 hours
measure: t1/2 (terminal half-life of the analyte in plasma)
timeFrame: up to 72 hours
measure: MRTpo (mean residence time of the analyte in the body after peroral administration)
timeFrame: up to 72 hours
measure: CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
timeFrame: up to 72 hours
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
timeFrame: up to 72 hours
measure: Number of subjects with clinically significant findings in vital signs
timeFrame: up to 7 days after last drug administration
measure: Number of subjects with clinically significant findings in 12-lead electrocardiogram (ECG)
timeFrame: up to 7 days after last drug administration
measure: Number of subjects with clinically significant findings in laboratory tests
timeFrame: up to 7 days after last drug administration
measure: Number of subjects with adverse events
timeFrame: up to 7 days after last drug administration
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: up to 7 days after last drug administration
Other outcomes:
Locations:
Study officials:
References: