Relative Bioavailability BI 10773 and Metformin in Healthy Male Volunteers

Relative Bioavailability of Both BI 10773 and Metformin After Coadministration Compared to Multiple Oral Doses of BI 10773 (50 mg q.d.) Alone and Metformin (1000 mg b.i.d.) Alone to Healthy Male Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study)

The objective was to investigate a possible drug-drug interaction between BI 10773 and metformin when co-administered as multiple oral doses. Therefore, the relative bioavailabilities of BI 10773 and metformin were determined when both drugs were given in combination compared with BI 10773 or metformin given alone.

Study Overview

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

• 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: No
• 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 (Blood Pressure), PR (Pulse Rate)), 12-lead ECG (Electrocardiogram), 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, 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/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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel 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 once daily from day 1 to 4 and metformin twice daily from day 1 to 3 and once in the morning on day 4; Treatment C: metformin twice daily from day 1 to 3 and once in the morning on day 4	Drug: Metformin; Drug: BI 10773
Experimental: Sequence CAB; Treatment C: metformin twice daily from day 1 to 3 and once in the morning on day 4; Treatment A: BI 10773 once daily from day 1 to 5; Treatment B: BI 10773 once daily from day 1 to 4 and metformin twice daily from day 1 to 3 and once in the morning on day 4	Drug: Metformin; Drug: BI 10773

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)	up to 7 days
Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)	up to 7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 40 days
C24,N (concentration of analyte in plasma at 24 hours post-drug administration after administration of the Nth dose) of BI 10773	up to 7 days
C12,N (concentration of analyte in plasma at 12 hours post-drug administration after administration of the Nth dose) of metformin	up to 7 days
λz,ss (terminal half-life of the analyte in plasma)	up to 7 days
t½,ss (terminal half-life of the analyte in plasma at steady state)	up to 7 days
tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ)	up to 7 days
MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration)	up to 7 days
CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)	up to 7 days
Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration)	up to 7 days
Aet1-t2,ss (amount of analyte eliminated in urine at steady state over a uniform dosing interval τ)	1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
fet1-t2,ss (fraction of analyte excreted unchanged in urine at steady state over a uniform dosing interval τ)	1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
CLR,ss (renal clearance of the analyte at steady state) of BI 10773 and metformin	1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
Urinary glucose excretion (UGE)	1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
Number of patients with abnormal findings in physical examination	Baseline and within 3-14 days after last study drug 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 study drug administration
Number of patients with abnormal findings in 12-lead ECG (electrocardiogram)	Baseline and within 3-14 days after last study drug administration
Number of patients with abnormal changes in clinical laboratory tests	Baseline, day 1, 4, 5 and within 3-14 days after last study drug administration
Assessment of tolerability by investigator on a 4-point scale	Within 3-14 days after last study 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, 2009
• Primary Completion (Actual): March 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; Sodium-Glucose Transporter 2 Inhibitors; Metformin; Empagliflozin
• Other Study ID Numbers: 1245.6