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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01907113
First received: July 15, 2013
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: BI 10773
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    Maximum concentration of Empagliflozin in plasma


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Time from last dosing to maximum concentration of Empagliflozin in plasma (tmax)

  • 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 ] [ Designated as safety issue: No ]
    Terminal half-life of Empagliflozin (t1/2) and Mean residence time of Empagliflozin in the body

  • 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 ] [ Designated as safety issue: No ]
    Terminal rate constant in plasma (Lz)

  • 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 ] [ Designated as safety issue: No ]
    Apparent clearance of the analyte in the plasma after extravascular administration

  • 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 ] [ Designated as safety issue: No ]
    Apparent volume of distribution during the terminal phase Lz

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    Amount of analyte that is eliminated in urine over the time interval 0-96 hours.

  • 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 ] [ Designated as safety issue: No ]
    Fraction of analyte excreted unchanged in urine from time point 0-96 hours.

  • 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 ] [ Designated as safety issue: No ]
    Renal Clearance of the Analyte in Plasma After Extravascular Administration for time interval 0-96 hours.

  • %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 ] [ Designated as safety issue: No ]
    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

  • Plasma Protein Binding [ Time Frame: 1 h before drug administration and 1:30 and 3:00 h after drug administration ] [ Designated as safety issue: No ]

    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.


  • 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) ] [ Designated as safety issue: No ]
    Change from baseline in total urinary glucose excretion

  • Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements [ Time Frame: Drug administration until end-of-study-examination, 5 days ] [ Designated as safety issue: No ]
    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

  • Assessment of Tolerability by Investigator [ Time Frame: Drug administration until end-of-study-examination, 5 days ] [ Designated as safety issue: No ]
    Tolerability was assessed by the investigator based on adverse events and the laboratory evaluation.


Enrollment: 40
Study Start Date: July 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01907113

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

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01907113     History of Changes
Other Study ID Numbers: 1245.12, 2008-006086-86
Study First Received: July 15, 2013
Results First Received: May 16, 2014
Last Updated: July 11, 2014
Health Authority: Germany: BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte)

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Renal Insufficiency
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on September 16, 2014