Clinical trial NCT01216397: Relative Bioavailability of Two Different Batches of a Linagliptin / Metformin Combination Tablet in Healthy Volunteers
Official title: Relative Bioavailability of Two Different Batches of a 2.5 mg Linagliptin / 1000 mg Metformin Fixed Dose Combination Tablet (FDC) 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: 2010-10-07
Enrollment: 40
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion criteria:

1. Healthy males and females according to the following criteria: Based upon a complete medical history, including physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
2. Age 21 to 50 years (incl.)
3. Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.)
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the 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 one 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 3 pipes daily)
12. Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in males)
13. Drug abuse
14. Blood donation (more than 100 mL within four weeks prior to day 1 of visit 2)
15. Any laboratory value outside the reference range that is 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 1 month before study or within 2 months after study completion
18. 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).
19. Lactation

Primary outcomes:
measure: Linagliptin: Maximum Measured Concentration (Cmax)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: Cmax
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: AUC0-tz
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Secondary outcomes:
measure: Linagliptin: AUC0-infinity
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Linagliptin: λz (Terminal Elimination Rate Constant in Plasma)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: t1/2 (Terminal Half-life of the Analyte in Plasma)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: AUC0-infinity
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: Tmax
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: λz (Terminal Elimination Rate Constant in Plasma)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: CL/F
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Metformin: Vz/F
timeFrame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
measure: Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
timeFrame: Day 1 to 4 for period 1, and day 36 to 39 for period 2
measure: Participants With Treatment Emergent Adverse Events
timeFrame: Day 1 to 4 for period 1, and day 36 to 39 for period 2
measure: Participants Who Discontinued the Trial Because of an Adverse Event
timeFrame: Day 1 to 4 for period 1, and day 36 to 39 for period 2
measure: Assessment of Tolerability by the Investigator
timeFrame: Day 1 to 4 for period 1, and day 36 to 39 for period 2
Other outcomes:
Locations:
city: Ingelheim
country: Germany
facility: 1288.6.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: