Back to results4 Weeks Treatment With Empagliflozin (BI 10773) in Japanese Type 2 Diabetic Patients (T2DM)
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Placebo (middle dose)
Placebo
BI 10773
BI 10773
BI 10773
Placebo (high dose)
BI 10773
Placebo (low dose)
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2
Eligibility Criteria
Inclusion criteria:
- Japanese male or female patients with T2DM treated with diet and exercise alone or with one hypoglycaemic drug other than glitazones.
Hemoglobin A1c (HbA1c) at screening (Visit 1)
- For patients treated with 1 other oral antidiabetic drug: HbA1c between 6.5% and 9.0%.
- For patients not treated with any antidiabetic drug: HbA1c between 7.0% and 10.0%.
- Age between 20 and 70 years
- Body mass index (BMI) between18.0 and 40.0 kg/m2
- Signed and dated written informed consent before admission to the trial in accordance with the Good Clinical Practice (GCP) and the local legislation.
Exclusion criteria:
- Antidiabetic treatment with insulin or glitazones within 3 months before obtaining informed consent or with more than 1 oral hypoglycaemic agent at the time of informed consent
- Fasted blood glucose of >240 mg/dL (>13.3 mmol/L) or a randomly determined blood glucose level of >400 mg/dL (22.2 mmol/L) on 2 consecutive days during wash-out period.
- Myocardial infarction, stroke, or transient ischaemic attack within 6 months before informed consent.
Clinically relevant concomitant diseases other than T2DM, hyperlipidaemia, and medically treated hypertension before the first administration such as
- Renal insufficiency (calculated estimated glomerular filtration rate <60)
- Cardiac insufficiency of New York Heart Association (NYHA) II-IV or other known cardiovascular diseases including hypertension of >160/95 mmHg,
- Neurological disorders (such as epilepsy) or psychiatric disorders
- Acute or clinically relevant chronic infections (e.g., human immunodeficiency virus, hepatitis, repeated urogenital infections)
- Any gastrointestinal, hepatic, respiratory, endocrine, or immunological disorder
Patients under treatment with any concomitant medication except for the following drugs at the time of informed consent.:
- Statins.
- Antihypertensives (diuretics not allowed)
- alpha-Blockers for benign prostate hypertrophy
- Occasional use of acetylsalicylic acid, ibuprofen, or paracetamol
- Additional inclusion/exclusion criteria apply
Sites / Locations
- 1245.15.003 Boehringer Ingelheim Investigational Site
- 1245.15.002 Boehringer Ingelheim Investigational Site
- 1245.15.001 Boehringer Ingelheim Investigational Site
- 1245.15.005 Boehringer Ingelheim Investigational Site
- 1245.15.004 Boehringer Ingelheim Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
BI 10773 low dose quaque die (QD)
BI 10773 mid-low dose QD
BI 10773 mid-high dose QD
BI 10773 high dose QD
Placebo
Arm Description
patient to receive a BI 10773 low dose tablet and a placebo tablet once daily
patient to receive a BI 10773 middle dose tablet and a placebo tablet once daily
patient to receive two tablets of BI 10773 middle dose once daily
patient to receive a BI 10773 high dose tablet and a placebo tablet once daily
patient to receive two tablets of placebo once daily
Outcomes
Primary Outcome Measures
Change From Baseline in Urine Glucose Excretion
Change from baseline in Urine glucose excretion to 28 days
Change From Baseline in Fasting Plasma Glucose
Change from baseline in Fasting plasma glucose to 28 days
Change From Baseline in 8-point Glucose
Change from baseline in 8-point glucose to 27 days
Secondary Outcome Measures
Change From Baseline in HbA1c
Change from baseline in HbA1c to 28 days
Change From Baseline in Fructosamine
Change from baseline in Fructosamine to 28 days
Change From Baseline in 1,5-anhydroglucitol
Change from baseline in 1,5-anhydroglucitol to 28 days
Change From Baseline in Fasting Insulin
Change from baseline in Fasting insulin to 28 days
Change From Baseline in the Area Under the Curve of Plasma Glucose Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
Change from baseline in the area under the curve of plasma glucose levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days
Change From Baseline in the Area Under the Curve of Glucagon Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
Change from baseline in the area under the curve of glucagon levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days
Change From Baseline in the Area Under the Curve of Insulin Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
Change from baseline in the area under the curve of insulin levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days
AUCτ,1
Area under the concentration-time curve of the analyte in plasma after administration of the first dose over a uniform dosing interval τ
AUC0-tz
area under the concentration-time curve of the analyte in plasma over the time interval from 0 to last quantifiable plasma concentration
AUC0-∞
area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity
Cmax
maximum measured concentration of the analyte in plasma
t1/2
terminal half-life of the analyte in plasma
CL/F
apparent clearance of the analyte in plasma after extravascular administration
Vz/F
apparent volume of distribution during the terminal phase λz following an extravascular dose
Ae0-24
amount of the analyte that is eliminated in urine over the time interval 0 to 24
fe0-24
fraction of the analyte excreted unchanged in urine from time interval 0 to 24
CLR,0-24
renal clearance of the analyte in plasma after extravascular administration - based on 0-24 hours data
AUCτ,ss
area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ at steady state
Cmax,ss
maximum measured concentration of the analyte in plasma at steady state
t1/2,ss
terminal half-life of the analyte in plasma at steady state
CL/F,ss
apparent clearance of the analyte in plasma after extravascular administration at steady state
Vz/F,ss
apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state
RA,Cmax
accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on Cmax
RA,AUC
accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on AUCτ
Ae0-24,ss
amount of the analyte that is eliminated in urine at steady state over the time interval 0 to 24
fe0-24,ss
fraction of the analyte excreted unchanged in urine at steady state from time interval 0 to 24
CLR,ss
renal clearance of the analyte at steady state determined over the dosing interval τ
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00885118
Brief Title
4 Weeks Treatment With Empagliflozin (BI 10773) in Japanese Type 2 Diabetic Patients (T2DM)
Official Title
A Phase II, Randomised, Double-blind, Placebo-controlled, Multiple Dose Study to Evaluate Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Once Daily Oral Administration of BI 10773 (1 mg, 5 mg, 10 mg, and 25 mg) for 28 Days in Japanese Patients With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
The objective of this trial is to evaluate the pharmacodynamics, pharmacokinetics, safety, and tolerability of once daily oral administration of BI 10773 administered for 28 days in Japanese patients with T2DM.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BI 10773 low dose quaque die (QD)
Arm Type
Experimental
Arm Description
patient to receive a BI 10773 low dose tablet and a placebo tablet once daily
Arm Title
BI 10773 mid-low dose QD
Arm Type
Experimental
Arm Description
patient to receive a BI 10773 middle dose tablet and a placebo tablet once daily
Arm Title
BI 10773 mid-high dose QD
Arm Type
Experimental
Arm Description
patient to receive two tablets of BI 10773 middle dose once daily
Arm Title
BI 10773 high dose QD
Arm Type
Experimental
Arm Description
patient to receive a BI 10773 high dose tablet and a placebo tablet once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
patient to receive two tablets of placebo once daily
Intervention Type
Drug
Intervention Name(s)
Placebo (middle dose)
Intervention Description
Placebo tablets once a day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets once a day
Intervention Type
Drug
Intervention Name(s)
BI 10773
Intervention Description
BI 10773 middle dose tablets once a day
Intervention Type
Drug
Intervention Name(s)
BI 10773
Intervention Description
BI 10773 high dose tablets once a day
Intervention Type
Drug
Intervention Name(s)
BI 10773
Intervention Description
BI 10773 middle dose tablets once a day
Intervention Type
Drug
Intervention Name(s)
Placebo (high dose)
Intervention Description
Placebo tablets once a day
Intervention Type
Drug
Intervention Name(s)
BI 10773
Intervention Description
BI 10773 low dose tablets once a day
Intervention Type
Drug
Intervention Name(s)
Placebo (low dose)
Intervention Description
Placebo tablets once a day
Primary Outcome Measure Information:
Title
Change From Baseline in Urine Glucose Excretion
Description
Change from baseline in Urine glucose excretion to 28 days
Time Frame
baseline and 28 days
Title
Change From Baseline in Fasting Plasma Glucose
Description
Change from baseline in Fasting plasma glucose to 28 days
Time Frame
baseline and 28 days
Title
Change From Baseline in 8-point Glucose
Description
Change from baseline in 8-point glucose to 27 days
Time Frame
baseline and 27 days
Secondary Outcome Measure Information:
Title
Change From Baseline in HbA1c
Description
Change from baseline in HbA1c to 28 days
Time Frame
baseline and 28 days
Title
Change From Baseline in Fructosamine
Description
Change from baseline in Fructosamine to 28 days
Time Frame
baseline and 28 days
Title
Change From Baseline in 1,5-anhydroglucitol
Description
Change from baseline in 1,5-anhydroglucitol to 28 days
Time Frame
baseline and 28 days
Title
Change From Baseline in Fasting Insulin
Description
Change from baseline in Fasting insulin to 28 days
Time Frame
baseline and 28 days
Title
Change From Baseline in the Area Under the Curve of Plasma Glucose Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
Description
Change from baseline in the area under the curve of plasma glucose levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days
Time Frame
baseline and 28 days
Title
Change From Baseline in the Area Under the Curve of Glucagon Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
Description
Change from baseline in the area under the curve of glucagon levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days
Time Frame
baseline and 28 days
Title
Change From Baseline in the Area Under the Curve of Insulin Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
Description
Change from baseline in the area under the curve of insulin levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days
Time Frame
baseline and 28 days
Title
AUCτ,1
Description
Area under the concentration-time curve of the analyte in plasma after administration of the first dose over a uniform dosing interval τ
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
Title
AUC0-tz
Description
area under the concentration-time curve of the analyte in plasma over the time interval from 0 to last quantifiable plasma concentration
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
Title
AUC0-∞
Description
area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
Title
Cmax
Description
maximum measured concentration of the analyte in plasma
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
Title
t1/2
Description
terminal half-life of the analyte in plasma
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
Title
CL/F
Description
apparent clearance of the analyte in plasma after extravascular administration
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
Title
Vz/F
Description
apparent volume of distribution during the terminal phase λz following an extravascular dose
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration
Title
Ae0-24
Description
amount of the analyte that is eliminated in urine over the time interval 0 to 24
Time Frame
0-5, 5-12, 12-24 hour after first drug administration
Title
fe0-24
Description
fraction of the analyte excreted unchanged in urine from time interval 0 to 24
Time Frame
0-5, 5-12, 12-24 hour after first drug administration
Title
CLR,0-24
Description
renal clearance of the analyte in plasma after extravascular administration - based on 0-24 hours data
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min, 0-5h, 5-12h, 12-24h after first drug administration
Title
AUCτ,ss
Description
area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ at steady state
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration
Title
Cmax,ss
Description
maximum measured concentration of the analyte in plasma at steady state
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration
Title
t1/2,ss
Description
terminal half-life of the analyte in plasma at steady state
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration
Title
CL/F,ss
Description
apparent clearance of the analyte in plasma after extravascular administration at steady state
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration
Title
Vz/F,ss
Description
apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration
Title
RA,Cmax
Description
accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on Cmax
Time Frame
Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration, and predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration
Title
RA,AUC
Description
accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on AUCτ
Time Frame
Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration, and predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration
Title
Ae0-24,ss
Description
amount of the analyte that is eliminated in urine at steady state over the time interval 0 to 24
Time Frame
0-5, 5-12, 12-24 hour after last drug administration
Title
fe0-24,ss
Description
fraction of the analyte excreted unchanged in urine at steady state from time interval 0 to 24
Time Frame
0-5, 5-12, 12-24 hour after last drug administration
Title
CLR,ss
Description
renal clearance of the analyte at steady state determined over the dosing interval τ
Time Frame
Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 0-5h, 5-12h, 12-24h after last drug administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Japanese male or female patients with T2DM treated with diet and exercise alone or with one hypoglycaemic drug other than glitazones.
Hemoglobin A1c (HbA1c) at screening (Visit 1)
For patients treated with 1 other oral antidiabetic drug: HbA1c between 6.5% and 9.0%.
For patients not treated with any antidiabetic drug: HbA1c between 7.0% and 10.0%.
Age between 20 and 70 years
Body mass index (BMI) between18.0 and 40.0 kg/m2
Signed and dated written informed consent before admission to the trial in accordance with the Good Clinical Practice (GCP) and the local legislation.
Exclusion criteria:
Antidiabetic treatment with insulin or glitazones within 3 months before obtaining informed consent or with more than 1 oral hypoglycaemic agent at the time of informed consent
Fasted blood glucose of >240 mg/dL (>13.3 mmol/L) or a randomly determined blood glucose level of >400 mg/dL (22.2 mmol/L) on 2 consecutive days during wash-out period.
Myocardial infarction, stroke, or transient ischaemic attack within 6 months before informed consent.
Clinically relevant concomitant diseases other than T2DM, hyperlipidaemia, and medically treated hypertension before the first administration such as
Renal insufficiency (calculated estimated glomerular filtration rate <60)
Cardiac insufficiency of New York Heart Association (NYHA) II-IV or other known cardiovascular diseases including hypertension of >160/95 mmHg,
Neurological disorders (such as epilepsy) or psychiatric disorders
Acute or clinically relevant chronic infections (e.g., human immunodeficiency virus, hepatitis, repeated urogenital infections)
Any gastrointestinal, hepatic, respiratory, endocrine, or immunological disorder
Patients under treatment with any concomitant medication except for the following drugs at the time of informed consent.:
Statins.
Antihypertensives (diuretics not allowed)
alpha-Blockers for benign prostate hypertrophy
Occasional use of acetylsalicylic acid, ibuprofen, or paracetamol
Additional inclusion/exclusion criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1245.15.003 Boehringer Ingelheim Investigational Site
City
Hachioji, Tokyo
Country
Japan
Facility Name
1245.15.002 Boehringer Ingelheim Investigational Site
City
Koganei, Tokyo
Country
Japan
Facility Name
1245.15.001 Boehringer Ingelheim Investigational Site
City
Nakano-ku, Tokyo
Country
Japan
Facility Name
1245.15.005 Boehringer Ingelheim Investigational Site
City
Suita, Osaka
Country
Japan
Facility Name
1245.15.004 Boehringer Ingelheim Investigational Site
City
Yokohama, Kanagawa
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
35472672
Citation
Tuttle KR, Levin A, Nangaku M, Kadowaki T, Agarwal R, Hauske SJ, Elsasser A, Ritter I, Steubl D, Wanner C, Wheeler DC. Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Diabetes Care. 2022 Jun 2;45(6):1445-1452. doi: 10.2337/dc21-2034.
Results Reference
derived
PubMed Identifier
29488164
Citation
Yasui A, Lee G, Hirase T, Kaneko T, Kaspers S, von Eynatten M, Okamura T. Empagliflozin Induces Transient Diuresis Without Changing Long-Term Overall Fluid Balance in Japanese Patients With Type 2 Diabetes. Diabetes Ther. 2018 Apr;9(2):863-871. doi: 10.1007/s13300-018-0385-5. Epub 2018 Feb 27.
Results Reference
derived
PubMed Identifier
24843716
Citation
Kanada S, Koiwai K, Taniguchi A, Sarashina A, Seman L, Woerle HJ. Pharmacokinetics, pharmacodynamics, safety and tolerability of 4 weeks' treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus. J Diabetes Investig. 2013 Nov 27;4(6):613-7. doi: 10.1111/jdi.12110. Epub 2013 Jun 25.
Results Reference
derived
PubMed Identifier
23940010
Citation
Riggs MM, Staab A, Seman L, MacGregor TR, Bergsma TT, Gastonguay MR, Macha S. Population pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with type 2 diabetes. J Clin Pharmacol. 2013 Oct;53(10):1028-38. doi: 10.1002/jcph.147. Epub 2013 Aug 13.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1245/1245.15_U10-2326-01-DS.pdf
Description
Related Info
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1245/1245.15_Literature.pdf
Description
Related Info
Learn more about this trial
4 Weeks Treatment With Empagliflozin (BI 10773) in Japanese Type 2 Diabetic Patients (T2DM)
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