Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of this study is to assess the effect of the different degrees of renal impairment on the pharmacokinetics, pharmacodynamics and safety of BI10773 following oral administration of high dose BI10773 as a single dose in Japanese patients with type 2 diabetes mellitus.
Interventions
DRUGBI10773
BI10773 medium dose tablet single dose
Sponsors
Eli Lilly and Company
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes patients * Glycosylated haemoglobin\>= 6.1% (Japan Diabetes Society) * Estimated glomerular filtration rate based on the modification of diet in renal disease-formula at screening , of \>= 15 mL/min/1.73m2
Exclusion criteria
* Any evidence of significant disease (other than renal impairment) * Moderate and severe concurrent liver function impairment * Gastrointestinal tract surgery, that might affect absorption and elimination of drugs * Diseases of the central nervous system (such as epilepsy), psychiatric disorders, or neurological disorders * Chronic or relevant acute infections * Participation in another trial with investigational drug administration within 30 days prior to study drug administration or during the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Urinary Glucose Excretion (UGE) | baseline and 24 hours | change from baseline in total urinary glucose excretion (UGE) to 24 hours |
| Area Under the Concentration Time Curve of the Analyte in Plasma | Predose and 20 minutes (min), 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 24h, 36h 48h, 72h and 96h after drug administration | Area under the concentration time curve of the analyte in plasma over the time interval from 0 to infinity |
| Maximum Concentration | Predose and 20 minutes (min), 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 24h, 36h 48h, 72h and 96h after drug administration | Maximum concentration of the analyte in plasma |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normal Renal Function 25 mg empagliflozin taken as a single dose for patients with normal renal function | 8 |
| Mild Renal Impairment 25 mg empagliflozin taken as a single dose for patients with mild renal impairment | 8 |
| Moderate Renal Impairment 25 mg empagliflozin taken as a single dose for patients with moderate renal impairment | 8 |
| Severe Renal Impairment 25 mg empagliflozin taken as a single dose for patients with severe renal impairment | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 3.1 | 67.5 years STANDARD_DEVIATION 4.4 | 65.9 years STANDARD_DEVIATION 5.5 | 62.0 years STANDARD_DEVIATION 7.9 | 65.5 years STANDARD_DEVIATION 5.6 |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 0 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 8 Participants | 6 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 2 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Concentration Time Curve of the Analyte in Plasma
Area under the concentration time curve of the analyte in plasma over the time interval from 0 to infinity
Time frame: Predose and 20 minutes (min), 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 24h, 36h 48h, 72h and 96h after drug administration
Population: Treated patients
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Area Under the Concentration Time Curve of the Analyte in Plasma | 7480 nmol*h/L | Geometric Coefficient of Variation 16.2 |
| Mild Renal Impairment | Area Under the Concentration Time Curve of the Analyte in Plasma | 9630 nmol*h/L | Geometric Coefficient of Variation 15.9 |
| Moderate Renal Impairment | Area Under the Concentration Time Curve of the Analyte in Plasma | 10800 nmol*h/L | Geometric Coefficient of Variation 9.55 |
| Severe Renal Impairment | Area Under the Concentration Time Curve of the Analyte in Plasma | 11400 nmol*h/L | Geometric Coefficient of Variation 40.4 |
90% CI: [105.962, 156.604]ANOVA
90% CI: [118.306, 174.848]ANOVA
90% CI: [125.287, 185.166]ANOVA
Primary
Change From Baseline in Total Urinary Glucose Excretion (UGE)
change from baseline in total urinary glucose excretion (UGE) to 24 hours
Time frame: baseline and 24 hours
Population: Treated patients who had complete urine sample (baseline and 24 hours) for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Change From Baseline in Total Urinary Glucose Excretion (UGE) | 74969.3 mg | 95% Confidence Interval 4840.68 |
| Mild Renal Impairment | Change From Baseline in Total Urinary Glucose Excretion (UGE) | 62577.4 mg | 95% Confidence Interval 5751.25 |
| Moderate Renal Impairment | Change From Baseline in Total Urinary Glucose Excretion (UGE) | 57889.0 mg | 95% Confidence Interval 4861.26 |
| Severe Renal Impairment | Change From Baseline in Total Urinary Glucose Excretion (UGE) | 23725.1 mg | 95% Confidence Interval 5235.06 |
Primary
Maximum Concentration
Maximum concentration of the analyte in plasma
Time frame: Predose and 20 minutes (min), 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 24h, 36h 48h, 72h and 96h after drug administration
Population: Treated patients
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Maximum Concentration | 1050 nmol/L | Geometric Coefficient of Variation 19.1 |
| Mild Renal Impairment | Maximum Concentration | 984 nmol/L | Geometric Coefficient of Variation 30.8 |
| Moderate Renal Impairment | Maximum Concentration | 971 nmol/L | Geometric Coefficient of Variation 26.2 |
| Severe Renal Impairment | Maximum Concentration | 990 nmol/L | Geometric Coefficient of Variation 43.8 |
90% CI: [72.236, 121.015]ANOVA
90% CI: [71.216, 119.305]ANOVA
90% CI: [72.63, 121.674]ANOVA