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

Phase 1CompletedNCT01907113

Boehringer Ingelheim40 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 2

Interventions

BI 10773DRUG

oral administration

BI 10773DRUG

oral administration

BI 10773DRUG

oral administration

BI 10773

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (2)

1245.12.1 Boehringer Ingelheim Investigational Site

Kiel, Germany

1245.12.2 Boehringer Ingelheim Investigational Site

Neuss, Germany

Outcomes

Primary Outcomes

AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity)

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.

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

Cmax (Maximum Concentration of the Analyte in Plasma)

Maximum concentration of Empagliflozin 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

Secondary Outcomes

Time to Maximum Concentration of the Analyte in Plasma

Time from last dosing to maximum concentration of Empagliflozin in plasma (tmax)

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

Half-life and Mean Residence Time of the Analyte in Plasma

Terminal half-life of Empagliflozin (t1/2) and Mean residence time of Empagliflozin in the body

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

Terminal rate constant in plasma (Lz)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

BI 10773DRUG

oral 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

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 Volume of Distribution During the Terminal Phase Lz

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

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)

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.

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

Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h)

Amount of analyte that is eliminated in urine over the time interval 0-96 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

fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours)

Fraction of analyte excreted unchanged in urine from time point 0-96 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

Renal Clearance of the Analyte in Plasma After Extravascular Administration

Renal Clearance of the Analyte in Plasma After Extravascular Administration for time interval 0-96 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

%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)

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

Plasma Protein Binding

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.

Time frame: 1 h before drug administration and 1:30 and 3:00 h after drug administration

Total Urinary Glucose Excretion (UGE)

Change from baseline in total urinary glucose excretion

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)

Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements

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

Time frame: Drug administration until end-of-study-examination, 5 days

Assessment of Tolerability by Investigator

Tolerability was assessed by the investigator based on adverse events and the laboratory evaluation.

Time frame: Drug administration until end-of-study-examination, 5 days