Relative Bioavailability of Pioglitazone After Co-administration With Different Doses of BI 10773 in Healthy Volunteers

Relative Bioavailability of Pioglitazone After Co-administration With Different Doses of BI 10773 in Healthy Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study)

The objective was to investigate the effect of different doses of BI 10773 on the bioavailability of pioglitazone after multiple oral doses of both drugs

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pioglitazone; Drug: BI 10773 - low dose; Drug: BI 10773 - medium dose; Drug: BI 10773 - high dose; Drug: Pioglitazone - low dose

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male subjects according to the following criteria:

   medical history, physical examination, vital signs ((blood pressure (BP), pulse rate (PR), 12-lead electrocardiogram (ECG)), clinical laboratory tests

2. Age 18 to 55 years (incl.)
3. 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 Practise (GCP) and the local legislation

Exclusion Criteria:

1. Any finding of the medical examination including blood pressure (BP), pulse rate (PR) and electrocardiogram (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/hypersensitivity (including allergy to drug or its excipients)
9. Intake of drugs with a long half-life (more than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
10. Participation in another trial with an investigational drug within two months prior to administration or during the trial
11. Smoker (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day)
12. Inability to refrain from smoking on trial days
13. Alcohol abuse (more than 30 g/day)
14. Drug abuse
15. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
16. Excessive physical activities (within one week prior to administration or during the trial)
17. Alanine aminotransferase (ALT) outside the normal range or any other laboratory value outside the reference range that is of clinical relevance
18. Inability to comply with dietary regimen of trial site
19. Galactose or lactose intolerance, galactose or glucose malabsorption

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pioglitazone	Drug: Pioglitazone
Experimental: Pioglitazone + BI 10773 low	Drug: Pioglitazone; Drug: BI 10773 - low dose
Experimental: Pioglitazone + BI 10773 medium	Drug: Pioglitazone; Drug: BI 10773 - medium dose
Experimental: Pioglitazone + BI 10773 high	Drug: Pioglitazone; Drug: BI 10773 - high dose
Experimental: Pioglitazone low + BI 10773 medium	Drug: BI 10773 - medium dose; Drug: Pioglitazone - low dose
Experimental: Pioglitazone + BI 10773 1 hour after Pioglitazone	Drug: Pioglitazone; Drug: BI 10773 - medium dose

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)	Before each dosing, up to 10 days
Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)	Before each dosing, up to 10 days

Secondary Outcome Measures

Outcome Measure	Time Frame
C24,N (concentration of the analyte in plasma at 24 h after administration of the Nth dose)	Before each dosing, up to 10 days
λz (terminal elimination rate constant of the analyte in plasma)	Before each dosing, up to 10 days
t½ (terminal half-life of the analyte in plasma)	Before each dosing, up to 10 days
tmax (time from last dosing to maximum measured concentration of the analyte in plasma)	Before each dosing, up to 10 days
MRTpo (mean residence time of the analyte in the body at steady state after oral administration)	Before each dosing, up to 10 days
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)	Before each dosing, up to 10 days
Vz/F (apparent volume of distribution during the terminal phase λz following extravascular administration)	Before each dosing, up to 10 days
Aet1-t2 (amount of analyte eliminated in urine over the time interval t1 to t2 )	Day1 (-1-0, 0-4, 4-8, 8-12, and 12-24 h), Day 7 (143-144, 144-148, 148-152, 152-156, and 156-168 h)
fet1-t2 (fraction of dose excreted unchanged in urine over the time interval t1 to t2)	Day1 (-1-0, 0-4, 4-8, 8-12, and 12-24 h), Day 7 (143-144, 144-148, 148-152, 152-156, and 156-168 h)
CLR (renal clearance of the analyte in plasma afer extravascular administration)	Day1 (-1-0, 0-4, 4-8, 8-12, and 12-24 h), Day 7 (143-144, 144-148, 148-152, 152-156, and 156-168 h)
Cmax (maximum concentration of the analyte in plasma)	Before each dosing, up to 10 days
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable plasma concentration)	Before each dosing, up to 10 days
AUCτ,1 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable plasma concentration within the first dosing interval)	Before each dosing, up to 10 days
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)	Before each dosing, up to 10 days
Metabolite to parent ratio	Before each dosing, up to 10 days
Number of patients with abnormal findings in physical examination	up to 30 days after drug administration
Number of patients with abnormal changes in laboratory parameters	up to 30 days after drug administration
Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG)	up to 30 days after drug administration
Number of patients with clinically significant changes in vital signs	up to 30 days after drug administration
Assessment of tolerability by investigator on a 4-point scale	up to 10 days
Number of patients with adverse events	up to 51 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

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

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; Pioglitazone; Empagliflozin
• Other Study ID Numbers: 1245.50