Relative Bioavailability of BI 10773 and Glimepiride in Healthy Male Volunteers

Relative Bioavailability of Both BI 10773 and Glimepiride After Co-administration Compared to Multiple Oral Doses of BI 10773 (50 mg q.d.) Alone and a Single Dose of Glimepiride (1 mg) Alone in Healthy Male Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study)

The objective was to investigate whether there was a drug-drug interaction between BI 10773 and glimepiride when co-administered. Therefore, the relative bioavailabilities of BI 10773 and glimepiride were determined when both drugs were given in combination compared to multiple oral doses of BI 10773 once daily alone and a single oral dose of glimepiride given alone.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 10773; Drug: Glimepiride

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male volunteers according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
• Age 18 to 50 years (incl.)
• BMI (Body Mass Index) 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

Exclusion Criteria:

• Any finding of the medical examination (including BP (Blood Pressure, PR (Pulse Rate) and ECG (Electrocardiogram)) 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/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (more than 30 g/day)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within one week prior to administration or during the trial)
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of trial site
• Glucose-6-phosphate dehydrogenase deficiency

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: Sequence ABC; Treatment A: BI 10773 once daily from day 1 to 5; Treatment B: BI 10773 and glimepiride once on day 1; Treatment C: Glimepiride once on day 1	Drug: BI 10773; Drug: Glimepiride
Experimental: Sequence CAB; Treatment C: Glimepiride once on day 1; Treatment A: BI 10773 once daily from day 1 to 5; Treatment B: BI 10773 and glimepiride once on day 1	Drug: BI 10773; Drug: Glimepiride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 10773	up to 5 days
Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 10773	up to 5 days
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) of glimepiride	up to 4 days
Cmax (maximum measured concentration of the analyte in plasma) of glimepiride	up to 4 days

Secondary Outcome Measures

Outcome Measure	Time Frame
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) of glimepiride	up to 4 days
tmax (time from dosing to the maximum concentration of the analyte in plasma) of glimepiride	up to 4 days
λz (terminal rate constant in plasma) of glimepiride	up to 4 days
t½ (terminal half-life of the analyte in plasma) of glimepiride	up to 4 days
MRTpo (mean residence time of the analyte in the body after po administration) of glimepiride	up to 4 days
CL/F (apparent clearance of the analyte in the plasma after extravascular administration) of glimepiride	up to 4 days
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) of glimepiride	up to 4 days
tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 10773	up to 5 days
Aet1-t2 (amount of analyte eliminated in urine over the time interval from t1 to t2) of glimepiride	1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1
fet1-t2 (fraction of analyte excreted unchanged in urine over the time interval from t1 to t2) of glimepiride	1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1
CLR (renal clearance of the analyte) of glimepiride	1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1
λz,ss (terminal rate constant of analyte in plasma at steady-state) of BI 10773	up to 5 days
t½,ss (terminal half-life of analyte in plasma at steady-state) of BI 10773	up to 5 days
MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration) of BI 10773	up to 5 days
CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) of BI 10773	up to 5 days
Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) of BI 10773	up to 5 days
Aet1-t2,ss (amount of analyte eliminated in urine at steady state over a uniform dosing interval τ) of BI 10773	1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 and 5
fet1-t2,ss (fraction of analyte excreted unchanged in urine at steady state over a uniform dosing interval τ) of BI 10773	1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 and 5
CLR,ss (renal clearance of the analyte at steady state) of BI 10773	1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 and 5
UGE0-24 (Urinary glucose excretion of the analyte in urine over the time interval from time zero to 24 h)	1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on days 1 and 5
Number of patients with abnormal findings in physical examination	Baseline and within 3-14 days after last glimepiride administration
Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate)	Baseline, day 1 and within 3-14 days after last glimepiride administration
Number of patients with abnormal findings in 12-lead ECG (electrocardiogram)	Baseline, day 1 and within 3-14 days after last glimepiride administration
Number of patients with abnormal findings in clinical laboratory tests	Baseline, day 1,4 and within 3-14 days after last glimepiride administration
Number of patients with adverse events	Up to 34 days
Assessment of tolerability by investigator on a 4-point scale	Within 3-14 days after last glimepiride administration
Number of patients with abnormal findings in glucose bedside tests	Pre-dose and 1, 2, 4, 7, 10, 14, 24 hours after glimepiride administration on day 1

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Estimate): June 24, 2014
• Last Update Submitted That Met QC Criteria: June 20, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin; Glimepiride
• Other Study ID Numbers: 1245.7