CompletedNCT00885118Updated Nov 25, 2014Results posted

4 Weeks Treatment With Empagliflozin (BI 10773) in Japanese Type 2 Diabetic Patients (T2DM)

A Phase 2 interventional study of Placebo (middle dose) and Placebo in Diabetes Mellitus, Type 2, sponsored by Boehringer Ingelheim. Completed at 5 sites in Japan. Open to participants aged 20 Years to 70 Years. Per ClinicalTrials.gov, last updated 2014-11-25.

Sponsored by Boehringer Ingelheim · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 100
Allocation: Randomized
Ages: 20 Years to 70 Years
Sex: All

Study 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.

Conditions studied

Diabetes Mellitus, Type 2

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In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 100 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

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Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 20 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double
Enrollment: 100 participants (actual)

Study arms

Experimental
BI 10773 low dose quaque die (QD)
patient to receive a BI 10773 low dose tablet and a placebo tablet once daily
Drug: BI 10773 · Drug: Placebo (low dose)
Experimental
BI 10773 mid-low dose QD
patient to receive a BI 10773 middle dose tablet and a placebo tablet once daily
Drug: Placebo (middle dose) · Drug: BI 10773
Experimental
BI 10773 mid-high dose QD
patient to receive two tablets of BI 10773 middle dose once daily
Drug: BI 10773
Experimental
BI 10773 high dose QD
patient to receive a BI 10773 high dose tablet and a placebo tablet once daily
Drug: BI 10773 · Drug: Placebo (high dose)
Placebo comparator
Placebo
patient to receive two tablets of placebo once daily
Drug: Placebo

Interventions

DrugPlacebo (middle dose)
Placebo tablets once a day
DrugPlacebo
Placebo tablets once a day
DrugBI 10773
BI 10773 middle dose tablets once a day
DrugBI 10773
BI 10773 high dose tablets once a day
DrugBI 10773
BI 10773 middle dose tablets once a day
DrugPlacebo (high dose)
Placebo tablets once a day
DrugBI 10773
BI 10773 low dose tablets once a day
DrugPlacebo (low dose)
Placebo tablets once a day

What researchers measure

Primary outcomes

Change From Baseline in Urine Glucose Excretion
Change from baseline in Urine glucose excretion to 28 days
Time frame: baseline and 28 days
Change From Baseline in Fasting Plasma Glucose
Change from baseline in Fasting plasma glucose to 28 days
Time frame: baseline and 28 days
Change From Baseline in 8-point Glucose
Change from baseline in 8-point glucose to 27 days
Time frame: baseline and 27 days

Secondary outcomes

Change From Baseline in HbA1c
Change from baseline in HbA1c to 28 days
Time frame: baseline and 28 days
Change From Baseline in Fructosamine
Change from baseline in Fructosamine to 28 days
Time frame: baseline and 28 days
Change From Baseline in 1,5-anhydroglucitol
Change from baseline in 1,5-anhydroglucitol to 28 days
Time frame: baseline and 28 days
Change From Baseline in Fasting Insulin
Change from baseline in Fasting insulin to 28 days
Time frame: baseline and 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
Time frame: baseline and 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
Time frame: baseline and 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
Time frame: baseline and 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
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
AUC0-tz
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
AUC0-∞
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
Cmax
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
t1/2
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
CL/F
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
Vz/F
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
Ae0-24
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
fe0-24
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
CLR,0-24
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
AUCτ,ss
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
Cmax,ss
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
t1/2,ss
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
CL/F,ss
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
Vz/F,ss
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
RA,Cmax
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
RA,AUC
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
Ae0-24,ss
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
fe0-24,ss
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
CLR,ss
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

Results

Posted Jun 16, 2014

Limitations and caveats

Additional secondary endpoints were listed in the original protocol. Those endpoints are of exploratory nature only and were not considered relevant for trial conclusions. For more information see tab "Full Text Review", section "More Information".

Participant flow

Participant flow — Overall Study
Milestone	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Started	21	19	21	20	19
Completed	20	19	20	20	18
Not completed	1	0	1	0	1
Withdrew: Adverse event	1	0	0	0	0
Withdrew: Withdrawal by subject	0	0	0	0	1
Withdrew: Other reason not defined above	0	0	1	0	0

Outcome measures

PrimaryChange From Baseline in Urine Glucose Excretion

Change from baseline in Urine glucose excretion to 28 days

Time frame:: baseline and 28 days
Reported as:: Least squares mean · mg

Change From Baseline in Urine Glucose Excretion
mg	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Change From Baseline in Urine Glucose Excretion	599.763 ± 4497.460	43428.245 ± 4598.593	81564.440 ± 4460.086	89189.527 ± 4704.967	86220.111 ± 4828.541

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = <0.0001 · Mean difference (final values): 42828.482 · 95% CI 29936.586 to 55720.378The baseline value was included as a continuous covariate.
Placebo vs Empa 5 mg · ANCOVA · p = <0.0001 · Mean difference (final values): 80964.677 · 95% CI 68437.160 to 93492.194The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = <0.0001 · Mean difference (final values): 88589.764 · 95% CI 75583.738 to 101595.790The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = <0.0001 · Mean difference (final values): 85620.348 · 95% CI 72484.181 to 98756.515The baseline value was included as a continuous covariate

PrimaryChange From Baseline in Fasting Plasma Glucose

Change from baseline in Fasting plasma glucose to 28 days

Time frame:: baseline and 28 days
Reported as:: Least squares mean · mg/dL

Change From Baseline in Fasting Plasma Glucose
mg/dL	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Change From Baseline in Fasting Plasma Glucose	-15.436 ± 2.860	-28.116 ± 2.965	-35.355 ± 2.865	-41.643 ± 3.009	-42.670 ± 3.089

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = 0.0030 · Mean difference (final values): -12.680 · 95% CI -20.936 to -4.424The baseline value was included as a continuous covariate
Placebo vs Empa 5 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -19.920 · 95% CI -27.919 to -11.921The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -26.208 · 95% CI -34.490 to -17.925The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -27.235 · 95% CI -35.586 to -18.884The baseline value was included as a continuous covariate

PrimaryChange From Baseline in 8-point Glucose

Change from baseline in 8-point glucose to 27 days

Time frame:: baseline and 27 days
Reported as:: Least squares mean · mg/dL

Change From Baseline in 8-point Glucose
mg/dL	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Change From Baseline in 8-point Glucose	-17.381 ± 3.932	-35.263 ± 4.121	-39.867 ± 3.903	-43.646 ± 4.113	-45.721 ± 4.187

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = 0.0030 · Mean difference (final values): -17.883 · 95% CI -29.529 to -6.236The baseline value was included as a continuous covariate
Placebo vs Empa 5 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -22.487 · 95% CI -33.308 to -11.665The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -26.265 · 95% CI -37.762 to -14.768The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -28.340 · 95% CI -39.665 to -17.015The baseline value was included as a continuous covariate

SecondaryChange From Baseline in HbA1c

Change from baseline in HbA1c to 28 days

Time frame:: baseline and 28 days
Reported as:: Least squares mean · percentage of HbA1c

Change From Baseline in HbA1c
percentage of HbA1c	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Change From Baseline in HbA1c	-0.420 ± 0.089	-0.659 ± 0.093	-0.717 ± 0.090	-0.849 ± 0.094	-0.815 ± 0.096

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = 0.0705 · Mean difference (final values): -0.239 · 95% CI -0.498 to -0.020The baseline value was included as a continuous covariate
Placebo vs Empa 5 mg · ANCOVA · p = 0.0203 · Mean difference (final values): -0.296 · 95% CI -0.545 to -0.047The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = 0.0014 · Mean difference (final values): -0.429 · 95% CI -0.687 to -0.170The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = 0.0033 · Mean difference (final values): -0.395 · 95% CI -0.654 to -0.135The baseline value was included as a continuous covariate

SecondaryChange From Baseline in Fructosamine

Change from baseline in Fructosamine to 28 days

Time frame:: baseline and 28 days
Reported as:: Least squares mean · umol/L

Change From Baseline in Fructosamine
umol/L	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Change From Baseline in Fructosamine	-8.436 ± 12.289	4.091 ± 12.663	-2.453 ± 12.362	-26.294 ± 12.933	-28.275 ± 13.282

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = 0.4823 · Mean difference (final values): 12.527 · 95% CI -22.757 to 47.811The baseline value was included as a continuous covariate
Placebo vs Empa 5 mg · ANCOVA · p = 0.7305 · Mean difference (final values): 5.984 · 95% CI -28.422 to 40.390The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = 0.3213 · Mean difference (final values): -17.858 · 95% CI -53.438 to 17.721The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = 0.2768 · Mean difference (final values): -19.838 · 95% CI -55.869 to 16.192The baseline value was included as a continuous covariate

SecondaryChange From Baseline in 1,5-anhydroglucitol

Change from baseline in 1,5-anhydroglucitol to 28 days

Time frame:: baseline and 28 days
Reported as:: Least squares mean · ug/mL

Change From Baseline in 1,5-anhydroglucitol
ug/mL	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Change From Baseline in 1,5-anhydroglucitol	1.174 ± 0.439	-3.018 ± 0.581	-3.435 ± 0.615	-2.863 ± 0.622	-3.713 ± 0.982

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -4.192 · 95% CI -5.653 to -2.731The baseline value was included as a continuous covariate
Placebo vs Empa 5 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -4.609 · 95% CI -6.126 to -3.091The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -4.036 · 95% CI -5.565 to -2.508The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -4.887 · 95% CI -7.048 to -2.726The baseline value was included as a continuous covariate

SecondaryChange From Baseline in Fasting Insulin

Change from baseline in Fasting insulin to 28 days

Time frame:: baseline and 28 days
Reported as:: Least squares mean · uU/mL

Change From Baseline in Fasting Insulin
uU/mL	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Change From Baseline in Fasting Insulin	-0.387 ± 0.287	-0.866 ± 0.295	-0.766 ± 0.287	-1.730 ± 0.301	-1.643 ± 0.312

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = 0.2498 · Mean difference (final values): -0.480 · 95% CI -1.302 to 0.343The baseline value was included as a continuous covariate
Placebo vs Empa 5 mg · ANCOVA · p = 0.3544 · Mean difference (final values): -0.379 · 95% CI -1.189 to 0.430The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = 0.0018 · Mean difference (final values): -1.343 · 95% CI -2.171 to -0.516The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = 0.0037 · Mean difference (final values): -1.257 · 95% CI -2.094 to -0.419The baseline value was included as a continuous covariate

SecondaryChange 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

Time frame:: baseline and 28 days
Reported as:: Least squares mean · hr*mg/dL

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)
hr*mg/dL	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
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)	-81.357 ± 10.481	-176.771 ± 10.924	-190.837 ± 10.554	-212.693 ± 11.023	-217.698 ± 11.247

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -95.414 · 95% CI -125.995 to -64.833The baseline value was included as a continuous covariate
Placebo vs Empa 5 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -109.480 · 95% CI -138.633 to -80.327The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -131.336 · 95% CI -161.848 to -100.824The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = <0.0001 · Mean difference (final values): -136.341 · 95% CI -166.860 to -105.823The baseline value was included as a continuous covariate

SecondaryChange 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

Time frame:: baseline and 28 days
Reported as:: Least squares mean · hr*pg/mL

Change From Baseline in the Area Under the Curve of Glucagon Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
hr*pg/mL	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Change From Baseline in the Area Under the Curve of Glucagon Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)	-23.452 ± 9.177	-0.785 ± 9.383	7.124 ± 9.138	-17.478 ± 9.635	-12.437 ± 9.964

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = 0.0883 · Mean difference (final values): 22.668 · 95% CI -3.470 to 48.805The baseline value was included as a continuous covariate
Placebo vs Empa 5 mg · ANCOVA · p = 0.0203 · Mean difference (final values): 30.576 · 95% CI 4.859 to 56.293The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = 0.6541 · Mean difference (final values): 5.974 · 95% CI -20.434 to 32.382The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = 0.4206 · Mean difference (final values): 11.015 · 95% CI -16.036 to 38.066The baseline value was included as a continuous covariate

SecondaryChange 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

Time frame:: baseline and 28 days
Reported as:: Least squares mean · hr*uU/mL

Change From Baseline in the Area Under the Curve of Insulin Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)
hr*uU/mL	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Change From Baseline in the Area Under the Curve of Insulin Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)	2.948 ± 2.819	-5.921 ± 2.896	-11.396 ± 2.811	-12.695 ± 2.982	-7.170 ± 3.048

Statistical analysis

Placebo vs Empa 1 mg · ANCOVA · p = 0.0318 · Mean difference (final values): -8.869 · 95% CI -16.949 to -0.789The baseline value was included as a continuous covariate
Placebo vs Empa 5 mg · ANCOVA · p = 0.0005 · Mean difference (final values): -14.344 · 95% CI -22.225 to -6.462The baseline value was included as a continuous covariate
Placebo vs Empa 10 mg · ANCOVA · p = 0.0003 · Mean difference (final values): -15.642 · 95% CI -23.853 to -7.432The baseline value was included as a continuous covariate
Placebo vs Empa 25 mg · ANCOVA · p = 0.0164 · Mean difference (final values): -10.118 · 95% CI -18.339 to -1.897The baseline value was included as a continuous covariate

SecondaryAUCτ,1

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
Reported as:: Geometric mean · nmol*h/L

AUCτ,1
nmol*h/L	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
AUCτ,1	216 ± 18.4	938 ± 44.2	2040 ± 19.4	5190 ± 18.6

SecondaryAUC0-tz

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
Reported as:: Geometric mean · nmol*h/L

AUC0-tz
nmol*h/L	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
AUC0-tz	216 ± 18.4	937 ± 44.2	2040 ± 19.5	5180 ± 18.6

SecondaryAUC0-∞

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
Reported as:: Geometric mean · nmol*h/L

AUC0-∞
nmol*h/L	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
AUC0-∞	249 ± 15.5	1070 ± 44.5	2320 ± 18.1	5930 ± 18.6

SecondaryCmax

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
Reported as:: Geometric mean · nmol/L

Cmax
nmol/L	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Cmax	38.5 ± 28.8	166 ± 47.6	358 ± 29.1	844 ± 15.7

Secondaryt1/2

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
Reported as:: Geometric mean · hour

t1/2
hour	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
t1/2	9.55 ± 14.8	9.09 ± 15.0	9.14 ± 13.3	9.26 ± 15.8

SecondaryCL/F

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
Reported as:: Geometric mean · mL/min

CL/F
mL/min	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
CL/F	149 ± 15.5	173 ± 44.5	159 ± 18.1	156 ± 18.6

SecondaryVz/F

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
Reported as:: Geometric mean · Liter

Vz/F
Liter	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Vz/F	123 ± 26.1	136 ± 46.3	126 ± 25.5	125 ± 25.3

SecondaryAe0-24

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
Reported as:: Geometric mean · nmol

Ae0-24
nmol	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Ae0-24	338 ± 23.7	1640 ± 56.2	3460 ± 17.5	8550 ± 17.0

Secondaryfe0-24

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
Reported as:: Geometric mean · percentage of Ae0-24 (to dosage)

fe0-24
percentage of Ae0-24 (to dosage)	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
fe0-24	15.2 ± 23.7	14.8 ± 56.2	15.6 ± 17.5	15.4 ± 17.0

SecondaryCLR,0-24

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
Reported as:: Geometric mean · mL/min

CLR,0-24
mL/min	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
CLR,0-24	25.7 ± 21.2	28.7 ± 27.3	28.3 ± 24.4	27.5 ± 23.4

SecondaryAUCτ,ss

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
Reported as:: Geometric mean · nmol*h/L

AUCτ,ss
nmol*h/L	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
AUCτ,ss	277 ± 17.0	1270 ± 15.0	2580 ± 17.3	6330 ± 20.3

SecondaryCmax,ss

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
Reported as:: Geometric mean · nmol/L

Cmax,ss
nmol/L	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Cmax,ss	41.4 ± 32.3	182 ± 31.4	393 ± 28.0	836 ± 29.2

Secondaryt1/2,ss

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
Reported as:: Geometric mean · hour

t1/2,ss
hour	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
t1/2,ss	12.2 ± 45.5	11.9 ± 48.0	13.4 ± 37.7	16.4 ± 48.4

SecondaryCL/F,ss

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
Reported as:: Geometric mean · mL/min

CL/F,ss
mL/min	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
CL/F,ss	133 ± 17.0	146 ± 15.0	143 ± 17.3	146 ± 20.3

SecondaryVz/F,ss

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
Reported as:: Geometric mean · Liter

Vz/F,ss
Liter	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Vz/F,ss	141 ± 37.8	151 ± 48.6	166 ± 43.6	208 ± 51.6

SecondaryRA,Cmax

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
Reported as:: Geometric mean · ratio

RA,Cmax
ratio	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
RA,Cmax	1.08 ± 23.3	1.07 ± 54.2	1.16 ± 34.2	0.998 ± 30.4

SecondaryRA,AUC

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
Reported as:: Geometric mean · ratio

RA,AUC
ratio	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
RA,AUC	1.28 ± 9.21	1.32 ± 42.5	1.32 ± 13.1	1.23 ± 12.7

SecondaryAe0-24,ss

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
Reported as:: Geometric mean · nmol

Ae0-24,ss
nmol	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Ae0-24,ss	479 ± 27.2	2250 ± 44.5	4780 ± 18.6	11500 ± 24.3

Secondaryfe0-24,ss

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
Reported as:: Geometric mean · percentage of Ae0-24 (to dosage)

fe0-24,ss
percentage of Ae0-24 (to dosage)	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
fe0-24,ss	21.6 ± 27.2	20.3 ± 44.5	21.6 ± 18.6	20.8 ± 24.3

SecondaryCLR,ss

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
Reported as:: Geometric mean · mL/min

CLR,ss
mL/min	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
CLR,ss	28.8 ± 25.2	29.6 ± 40.5	30.9 ± 28.1	30.3 ± 28.3

Adverse events

Collected over Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo	—	0/21 (0%)	1/21 (4.8%)
Empa 1 mg	—	1/19 (5.3%)	6/19 (31.6%)
Empa 5 mg	—	0/21 (0%)	2/21 (9.5%)
Empa 10 mg	—	0/20 (0%)	5/20 (25%)
Empa 25 mg	—	0/19 (0%)	7/19 (36.8%)

Most frequent serious events

Most frequent serious events
Event	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
Transient ischaemic attackNervous system disorders	0/21	1/19	0/21	0/20	0/19

Most frequent other events

Showing 10 of 16

Most frequent other events
Event	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg
NasopharyngitisInfections and infestations	0/21	2/19	1/21	0/20	1/19
Abdominal pain upperGastrointestinal disorders	0/21	0/19	0/21	2/20	0/19
ConstipationGastrointestinal disorders	1/21	0/19	1/21	2/20	1/19
CystitisInfections and infestations	0/21	0/19	0/21	0/20	1/19
Dry eyeEye disorders	0/21	1/19	0/21	0/20	0/19
DiarrhoeaGastrointestinal disorders	0/21	1/19	0/21	0/20	1/19
ToothacheGastrointestinal disorders	0/21	0/19	0/21	0/20	1/19
EczemaSkin and subcutaneous tissue disorders	0/21	0/19	0/21	1/20	1/19
PollakiuriaRenal and urinary disorders	0/21	0/19	0/21	0/20	1/19
Oedema peripheralGeneral disorders	0/21	0/19	0/21	0/20	1/19

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg	Total
Mean	57.2 ± 10.0	58.6 ± 8.2	53.9 ± 9.9	55.8 ± 8.0	60.8 ± 8.7	57.2 ± 9.2

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo	Empa 1 mg	Empa 5 mg	Empa 10 mg	Empa 25 mg	Total
Female	5	3	1	3	4	16
Male	16	16	20	17	15	84

Study locations

5 sites

1245.15.003 Boehringer Ingelheim Investigational Site
Hachioji, Tokyo, Japan
1245.15.002 Boehringer Ingelheim Investigational Site
Koganei, Tokyo, Japan
1245.15.001 Boehringer Ingelheim Investigational Site
Nakano-ku, Tokyo, Japan
1245.15.005 Boehringer Ingelheim Investigational Site
Suita, Osaka, Japan
1245.15.004 Boehringer Ingelheim Investigational Site
Yokohama, Kanagawa, Japan

References and documents

Publications

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. PubMed 35472672 ↗
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. PubMed 29488164 ↗
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. PubMed 24843716 ↗
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. PubMed 23940010 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 25, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00885118
Lead sponsor: Boehringer Ingelheim
Responsible party: Sponsor
First posted: Apr 21, 2009
Start date: Apr 2009
Primary completion: Oct 2009
Results posted: Jun 16, 2014
Last update: Nov 25, 2014

Study contacts

Boehringer Ingelheim

study chair · Boehringer Ingelheim

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4 Weeks Treatment With Empagliflozin (BI 10773) in Japanese Type 2 Diabetic Patients (T2DM)

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