Bioequivalence of a 2.5 mg Linagliptin / 850 mg Metformin Fixed Dose Combination Tablet Compared With Single Linagliptin 2.5 mg and Metformin 850 mg Tablets in Healthy Volunteers

Bioequivalence of a 2.5 mg Linagliptin / 850 mg Metformin Fixed Dose Combination Tablet Compared With Single Linagliptin 2.5 mg and Metformin 850 mg Tablets Administered Together in Healthy Male and Female Volunteers (an Open-label, Randomised, Single-dose, Two-way Crossover, Phase I Trial)

Study to assess bioequivalence of a 2.5 mg linagliptin / 850 mg metformin fixed dose combination (FDC) tablet compared to single tablets of linagliptin 2.5 mg and metformin 850 mg administered together

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Linagliptin; Drug: Metformin; Drug: Linagliptin/Metformin FDC

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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) 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 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A (FDC)	Drug: Linagliptin/Metformin FDC
Active Comparator: Treatment B (single agents)	Drug: Linagliptin; Drug: Metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum measured concentration of the analyte in plasma)	up to 72 hours
AUC0-72 (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 h)	up to 72 hours
AUC0-∞ (area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity)	up to 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with clinically significant findings in vital signs	blood pressure, pulse rate	up to 7 days after drug administration
Number of subjects with clinically significant findings in laboratory tests		up to 7 days after drug administration
Number of subjects with adverse events		up to 7 days after drug administration
AUC0-∞ (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity)		up to 72 hours
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)		up to 72 hours
%AUCtz-∞ (percentage of AUCtz-∞ obtained by extrapolation)		up to 72 hours
AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)		up to 72 hours
λz (terminal elimination rate constant in plasma)		up to 72 hours
t1/2 (terminal half-life of the analyte in plasma)		up to 72 hours
MRTpo (mean residence time of the analyte in the body after peroral administration)		up to 72 hours
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)		up to 72 hours
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)		up to 72 hours
tmax (time from dosing to the maximum concentration of the analyte in plasma)		up to 72 hours
Number of subjects with clinically significant findings in 12-lead electrocardiogram (ECG)		up to 7 days after drug administration
Assessment of tolerability by investigator on a 4-point scale		up to 7 days after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: August 19, 2014
• First Submitted That Met QC Criteria: August 19, 2014
• First Posted (Estimate): August 20, 2014

Study Record Updates

• Last Update Posted (Estimate): August 20, 2014
• Last Update Submitted That Met QC Criteria: August 19, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Linagliptin
• Other Study ID Numbers: 1288.3