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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00885118
First received: April 20, 2009
Last updated: July 18, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Placebo (middle dose)
Drug: Placebo
Drug: BI 10773
Drug: Placebo (high dose)
Drug: Placebo (low dose)
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline in Urine Glucose Excretion [ Time Frame: baseline and 28 days ] [ Designated as safety issue: No ]
    Change from baseline in Urine glucose excretion to 28 days

  • Change From Baseline in Fasting Plasma Glucose [ Time Frame: baseline and 28 days ] [ Designated as safety issue: No ]
    Change from baseline in Fasting plasma glucose to 28 days

  • Change From Baseline in 8-point Glucose [ Time Frame: baseline and 27 days ] [ Designated as safety issue: No ]
    Change from baseline in 8-point glucose to 27 days


Secondary Outcome Measures:
  • Change From Baseline in HbA1c [ Time Frame: baseline and 28 days ] [ Designated as safety issue: No ]
    Change from baseline in HbA1c to 28 days

  • Change From Baseline in Fructosamine [ Time Frame: baseline and 28 days ] [ Designated as safety issue: No ]
    Change from baseline in Fructosamine to 28 days

  • Change From Baseline in 1,5-anhydroglucitol [ Time Frame: baseline and 28 days ] [ Designated as safety issue: No ]
    Change from baseline in 1,5-anhydroglucitol to 28 days

  • Change From Baseline in Fasting Insulin [ Time Frame: baseline and 28 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and 28 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and 28 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and 28 days ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    area under the concentration-time curve of the analyte in plasma over the time interval from 0 to last quantifiable plasma concentration

  • AUC0-∞ [ 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 ] [ Designated as safety issue: No ]
    area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity

  • Cmax [ 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 ] [ Designated as safety issue: No ]
    maximum measured concentration of the analyte in plasma

  • t1/2 [ 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 ] [ Designated as safety issue: No ]
    terminal half-life of the analyte in plasma

  • CL/F [ 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 ] [ Designated as safety issue: No ]
    apparent clearance of the analyte in plasma after extravascular administration

  • Vz/F [ 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 ] [ Designated as safety issue: No ]
    apparent volume of distribution during the terminal phase λz following an extravascular dose

  • Ae0-24 [ Time Frame: 0-5, 5-12, 12-24 hour after first drug administration ] [ Designated as safety issue: No ]
    amount of the analyte that is eliminated in urine over the time interval 0 to 24

  • fe0-24 [ Time Frame: 0-5, 5-12, 12-24 hour after first drug administration ] [ Designated as safety issue: No ]
    fraction of the analyte excreted unchanged in urine from time interval 0 to 24

  • CLR,0-24 [ 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 ] [ Designated as safety issue: No ]
    renal clearance of the analyte in plasma after extravascular administration - based on 0-24 hours data

  • AUCτ,ss [ 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 ] [ Designated as safety issue: No ]
    area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ at steady state

  • Cmax,ss [ 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 ] [ Designated as safety issue: No ]
    maximum measured concentration of the analyte in plasma at steady state

  • t1/2,ss [ 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 ] [ Designated as safety issue: No ]
    terminal half-life of the analyte in plasma at steady state

  • CL/F,ss [ 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 ] [ Designated as safety issue: No ]
    apparent clearance of the analyte in plasma after extravascular administration at steady state

  • Vz/F,ss [ 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 ] [ Designated as safety issue: No ]
    apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state

  • RA,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 ] [ Designated as safety issue: No ]
    accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on Cmax

  • RA,AUC [ 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 ] [ Designated as safety issue: No ]
    accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on AUCτ

  • Ae0-24,ss [ Time Frame: 0-5, 5-12, 12-24 hour after last drug administration ] [ Designated as safety issue: No ]
    amount of the analyte that is eliminated in urine at steady state over the time interval 0 to 24

  • fe0-24,ss [ Time Frame: 0-5, 5-12, 12-24 hour after last drug administration ] [ Designated as safety issue: No ]
    fraction of the analyte excreted unchanged in urine at steady state from time interval 0 to 24

  • CLR,ss [ 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 ] [ Designated as safety issue: No ]
    renal clearance of the analyte at steady state determined over the dosing interval τ


Enrollment: 100
Study Start Date: April 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
BI 10773 low dose tablets once a day
Drug: Placebo (low dose)
Placebo tablets once a day
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)
Placebo tablets once a day
Drug: BI 10773
BI 10773 middle dose tablets once a day
Experimental: BI 10773 mid-high dose QD
patient to receive two tablets of BI 10773 middle dose once daily
Drug: BI 10773
BI 10773 middle dose tablets once a day
Experimental: BI 10773 high dose QD
patient to receive a BI 10773 high dose tablet and a placebo tablet once daily
Drug: BI 10773
BI 10773 high dose tablets once a day
Drug: Placebo (high dose)
Placebo tablets once a day
Placebo Comparator: Placebo
patient to receive two tablets of placebo once daily
Drug: Placebo
Placebo tablets once a day

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
    • Beta-Blockers for benign prostate hypertrophy
    • Occasional use of acetylsalicylic acid, ibuprofen, or paracetamol
  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: NCT00885118

Locations
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, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00885118     History of Changes
Other Study ID Numbers: 1245.15
Study First Received: April 20, 2009
Results First Received: May 16, 2014
Last Updated: July 18, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

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

ClinicalTrials.gov processed this record on August 28, 2014