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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00885118
• Other study ID #: 1245.15
• Status: Completed
• Phase: Phase 2
• First received: April 20, 2009
• Last updated: November 13, 2014
• Start date: April 2009

Study information

• Verified date: November 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 70 Years

Eligibility

Inclusion criteria:

1. Japanese male or female patients with T2DM treated with diet and exercise alone or with one hypoglycaemic drug other than glitazones.

2. 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%.

3. Age between 20 and 70 years

4. Body mass index (BMI) between18.0 and 40.0 kg/m2

5. 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:

1. 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

2. 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.

3. Myocardial infarction, stroke, or transient ischaemic attack within 6 months before informed consent.

4. 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

5. 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

6. Additional inclusion/exclusion criteria apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Placebo (middle dose)
Placebo tablets once a day
• Placebo
Placebo tablets once a day
• BI 10773
BI 10773 middle dose tablets once a day
• BI 10773
BI 10773 high dose tablets once a day
• BI 10773
BI 10773 middle dose tablets once a day
• Placebo (high dose)
Placebo tablets once a day
• BI 10773
BI 10773 low dose tablets once a day
• Placebo (low dose)
Placebo tablets once a day

Locations

Country	Name	City	State
Japan	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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Urine Glucose Excretion	Change from baseline in Urine glucose excretion to 28 days	baseline and 28 days	No
Primary	Change From Baseline in Fasting Plasma Glucose	Change from baseline in Fasting plasma glucose to 28 days	baseline and 28 days	No
Primary	Change From Baseline in 8-point Glucose	Change from baseline in 8-point glucose to 27 days	baseline and 27 days	No
Secondary	Change From Baseline in HbA1c	Change from baseline in HbA1c to 28 days	baseline and 28 days	No
Secondary	Change From Baseline in Fructosamine	Change from baseline in Fructosamine to 28 days	baseline and 28 days	No
Secondary	Change From Baseline in 1,5-anhydroglucitol	Change from baseline in 1,5-anhydroglucitol to 28 days	baseline and 28 days	No
Secondary	Change From Baseline in Fasting Insulin	Change from baseline in Fasting insulin to 28 days	baseline and 28 days	No
Secondary	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	baseline and 28 days	No
Secondary	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	baseline and 28 days	No
Secondary	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	baseline and 28 days	No
Secondary	AUCt,1	Area under the concentration-time curve of the analyte in plasma after administration of the first dose over a uniform dosing interval t	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	No
Secondary	AUC0-tz	area under the concentration-time curve of the analyte in plasma over the time interval from 0 to last quantifiable plasma concentration	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	No
Secondary	AUC0-8	area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity	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	No
Secondary	Cmax	maximum measured concentration of the analyte in plasma	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	No
Secondary	t1/2	terminal half-life of the analyte in plasma	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	No
Secondary	CL/F	apparent clearance of the analyte in plasma after extravascular administration	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	No
Secondary	Vz/F	apparent volume of distribution during the terminal phase ?z following an extravascular dose	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	No
Secondary	Ae0-24	amount of the analyte that is eliminated in urine over the time interval 0 to 24	0-5, 5-12, 12-24 hour after first drug administration	No
Secondary	fe0-24	fraction of the analyte excreted unchanged in urine from time interval 0 to 24	0-5, 5-12, 12-24 hour after first drug administration	No
Secondary	CLR,0-24	renal clearance of the analyte in plasma after extravascular administration - based on 0-24 hours data	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	No
Secondary	AUCt,ss	area under the concentration-time curve of the analyte in plasma over a uniform dosing interval t at steady state	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	No
Secondary	Cmax,ss	maximum measured concentration of the analyte in plasma at steady state	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	No
Secondary	t1/2,ss	terminal half-life of the analyte in plasma at steady state	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	No
Secondary	CL/F,ss	apparent clearance of the analyte in plasma after extravascular administration at steady state	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	No
Secondary	Vz/F,ss	apparent volume of distribution during the terminal phase ?z following an extravascular dose at steady state	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	No
Secondary	RA,Cmax	accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval t, based on Cmax	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	No
Secondary	RA,AUC	accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval t, based on AUCt	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	No
Secondary	Ae0-24,ss	amount of the analyte that is eliminated in urine at steady state over the time interval 0 to 24	0-5, 5-12, 12-24 hour after last drug administration	No
Secondary	fe0-24,ss	fraction of the analyte excreted unchanged in urine at steady state from time interval 0 to 24	0-5, 5-12, 12-24 hour after last drug administration	No
Secondary	CLR,ss	renal clearance of the analyte at steady state determined over the dosing interval t	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	No

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