Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of BI 10773 in Type II Diabetes Patients With Different Degrees of Renal Impairment

Study Description

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Brief Summary:

Assessment of the effect of normal and impaired kidney function on the pharmacokinetics, pharmacodynamics and safety of BI 10773

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: BI 10773	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	40 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of a Single 50 mg Dose of BI 10773 in Patients With Different Degrees of Renal Impairment in Comparison to Subjects With Type 2 Diabetes and Normal Renal Function in a Monocentric, Open-label, Parallel-group, Phase 1 Trial
Study Start Date :	July 2009
Actual Primary Completion Date :	December 2009
Actual Study Completion Date :	December 2009

Arms and Interventions

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Arm	Intervention/treatment
Experimental: BI 10773 / Group 2; Single Dose Administration (type 2 diabetes and mild renal impairment)	Drug: BI 10773; oral administration
Experimental: BI 10773 / Group 3; Single Dose Administration (type 2 diabetes and moderate renal impairment)	Drug: BI 10773; oral administration
Experimental: BI 10773 / Group 4; Single Dose Administration (severe renal impairment 8)	Drug: BI 10773; oral administration
Experimental: BI 10773 / Group 5; Single Dose Administration (kidney failure)	Drug: BI 10773; oral administration
Experimental: BI 10773 / Group 1; Single Dose Administration (type 2 diabetes and normal renal function)	Drug: BI 10773; oral administration

Outcome Measures

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Primary Outcome Measures :

1. AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity) [ Time Frame: 1 hour (h) before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration ]
   Area under the concentration time curve of the analyte in plasma over the time interval from 0 to infinity. The areas under the curve were calculated using the linear up/log down algorithm. If a drug concentration was equal to or higher than the preceding concentration, the linear trapezoidal method was used. If the drug concentration was smaller than the preceding concentration, the logarithmic method was used.
2. Cmax (Maximum Concentration of the Analyte in Plasma) [ Time Frame: 1 hour (h) before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration ]
   Maximum concentration of Empagliflozin in plasma

Secondary Outcome Measures :

1. Time to Maximum Concentration of the Analyte in Plasma [ Time Frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration ]
   Time from last dosing to maximum concentration of Empagliflozin in plasma (tmax)
2. Half-life and Mean Residence Time of the Analyte in Plasma [ Time Frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration ]
   Terminal half-life of Empagliflozin (t1/2) and Mean residence time of Empagliflozin in the body
3. Terminal Rate Constant in Plasma [ Time Frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration ]
   Terminal rate constant in plasma (Lz)
4. Apparent Clearance of the Analyte in the Plasma After Extravascular Administration [ Time Frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration ]
   Apparent clearance of the analyte in the plasma after extravascular administration
5. Apparent Volume of Distribution During the Terminal Phase Lz [ Time Frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration ]
   Apparent volume of distribution during the terminal phase Lz
6. 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) [ Time Frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration ]
   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. The areas under the curve were calculated using the linear up/log down algorithm. If a drug concentration was equal to or higher than the preceding concentration, the linear trapezoidal method was used. If the drug concentration was smaller than the preceding concentration, the logarithmic method was used.
7. Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h) [ Time Frame: 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration ]
   Amount of analyte that is eliminated in urine over the time interval 0-96 hours.
8. fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours) [ Time Frame: 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration ]
   Fraction of analyte excreted unchanged in urine from time point 0-96 hours.
9. Renal Clearance of the Analyte in Plasma After Extravascular Administration [ Time Frame: 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration ]
   Renal Clearance of the Analyte in Plasma After Extravascular Administration for time interval 0-96 hours.
10. %AUCtz-∞ (Percentage of Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From the Time of the Last Quantifiable Data Point Extrapolated to Infinity) [ Time Frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration ]
    Percentage of area under the concentration-time curve of the analyte in plasma over the time interval from the time of the last quantifiable data point extrapolated to infinity
11. Plasma Protein Binding [ Time Frame: 1 h before drug administration and 1:30 and 3:00 h after drug administration ]

    Plasma protein binding is the percent of analyte binding to the plasma protein, pre-dose plasma samples were spiked with Empa 1000 nmol/L.

    The standard deviation is actually the coefficient of variation.

12. Total Urinary Glucose Excretion (UGE) [ Time Frame: 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration (Interval 24-0 h before drug administration only for baseline UGE) ]
    Change from baseline in total urinary glucose excretion
13. Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements [ Time Frame: Drug administration until end-of-study-examination, 5 days ]
    Number of participants with clinically relevant findings in physical examination, Vital Signs, Clinically Significant Abnormalities in Electrocardiogram (ECG) and Significant Changes from Baseline Laboratory Measurements
14. Assessment of Tolerability by Investigator [ Time Frame: Drug administration until end-of-study-examination, 5 days ]
    Tolerability was assessed by the investigator based on adverse events and the laboratory evaluation.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

1. Male and female subjects with type 2 diabetes
2. Renally impaired male or female subjects
3. Age 18 - 75 years
4. BMI 18 - 34 kg/m2, at least 45 kg for females (Body Mass Index)
5. Signed and dated written informed consent

Exclusion criteria:

1. Significant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders as judged by the investigator.
2. Relevant gastrointestinal tract surgery
3. Diseases of the central nervous system (such as epilepsy, seizures) or psychiatric disorders or relevant neurological disorders
4. History of relevant orthostatic hypotension, fainting spells or blackouts; systolic blood pressure < 100 or > 160 mm Hg, diastolic blood pressure < 60 or > 100 mm Hg, pulse rate < 50 or > 100 1/min
5. Chronic or relevant acute infections
6. History of allergy/hypersensitivity (including drug allergies) that are deemed relevant to the trial as judged by the investigator

7. Use within 10 days prior to administration or during the trial of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation. Co medication known to inhibit or induce P-glycoprotein or CYP3A is not allowed. Inhibitors of P-glycoprotein or CYP3A (cytochrom P3A) are e.g.

   • protease inhibitors, (e.g. ritonavir, lopinavir nelfinavir)
   • azole antimycotics, (itraconazole, ketoconazole, miconazole)
   • macrolid antibiotics, (clarithromycin, erythromycin)
   • amiodarone, cimetidine, diltiazem, fluvoxamine, mibefradil, nefazodone, verapamil, tacrolimus, quinidine, reserpine, cyclosporine A Inducers of P-gp or CYP3A are e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, ri-fampin, St. John's wort, troglitazone. In dubious cases, a case by case decision will be made after consultation with the sponsor.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Germany
1245.12.1 Boehringer Ingelheim Investigational Site
Kiel, Germany
1245.12.2 Boehringer Ingelheim Investigational Site
Neuss, Germany

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

Study Chair:	Boehringer Ingelheim	Boehringer Ingelheim

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT01907113 History of Changes
Other Study ID Numbers:	1245.12; 2008-006086-86 ( EudraCT Number: EudraCT )
First Posted:	July 24, 2013
Results First Posted:	July 14, 2014
Last Update Posted:	July 14, 2014
Last Verified:	July 2014

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Renal Insufficiency; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases	Kidney Diseases; Urologic Diseases; Empagliflozin; Hypoglycemic Agents; Physiological Effects of Drugs