A Study to Determine Acute (After First Dose) and Chronic (After 28 Days) Effects of Empagliflozin (BI 10773) on Pre and Postprandial Glucose Homeostasis in Patients With Impaired Glucose Tolerance and Type 2 Diabetes Mellitus and Healthy Subjects

NCT01248364 | Completed Phase 2 Results

• 2 other identifiers: 1245.392010-018708-99
• Study Type: interventional
• Target: 91
• Locations: 3 countries
• Sites: 3

Brief Summary

An open-label, phase II study to assess the acute and chronic effects of empagliflozin (BI 10773)on fasting and postprandial glucose homeostasis in patients with IGT and type 2 diabetes mellitus and assess the acute effects of empagliflozin in healthy subjects.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Fasting Plasma Glucose at Day 1

  Change from baseline of Fasting Plasma glucose (FPG) 3 hours and 35 minutes before meal at day 1

  Baseline and day 1

• Change From Baseline in Fasting Plasma Glucose at Day 28

  Change from baseline of Fasting Plasma glucose (FPG) 3 hours and 35 minutes before meal at day 28. Note, healthy subjects only received a single dose of empa so assessments at day 28 are not applicable

  Baseline and day 28

• Change From Baseline in Glucose Metabolism (Pre-meal and Postprandial Glucose), PPG iAUC 5h, at Day 1

  Change from baseline in the incremental area under the curve of postprandial plasma glucose from 0 to 5 hours (PPG iAUC 5h), defined as the area under the curve of timepoints 0 to 5 hours after meal reduced by the pre-meal plasma glucose at 0 hours.

  0 minutes (min), 15min, 30min, 45min, 1hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 4h 30min and 5h after meal at baseline and day 1

• Change From Baseline in Glucose Metabolism (Pre-meal and Postprandial Glucose), PPG iAUC 5h, at Day 28

  Change from baseline in the incremental area under the curve of postprandial plasma glucose from 0 to 5 hours (PPG iAUC 5h), defined as the area under the curve of timepoints 0 to 5 hours after meal reduced by the pre-meal plasma glucose at 0 hours. Note, healthy subjects only received a single dose of empa so assessments at day 28 are not applicable.

  0 minutes (min), 15min, 30min, 45min, 1hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 4h 30min and 5h after meal at baseline and day 28

Secondary Outcomes (6)

• Change From Baseline in Rate of Endogenous Glucose Production: Fast, at Day 1

  Baseline and day 1

• Change From Baseline in Rate of Endogenous Glucose Production: Fast, at Day 28

  Baseline and day 28

• Change From Baseline in Rate of Endogenous Glucose Production: AUC 5h, at Day 1

  0 minutes (min), 15min, 30min, 45min, 1hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 4h 30min and 5h after meal at baseline and day 1

• Change From Baseline in Rate of Endogenous Glucose Production: AUC 5h, at Day 28

  0 minutes (min), 15min, 30min, 45min, 1hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 4h 30min and 5h after meal at baseline and day 28

• Change From Baseline in Rate of Endogenous Glucose Production: iAUC 5h, at Day 1

  0 minutes (min), 15min, 30min, 45min, 1hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 4h 30min and 5h after drug administration at baseline and day 1

Study Arms (1)

BI 10773 Arm

EXPERIMENTAL

BI 10773 high dose once daily

Drug: BI 10773

Interventions

BI 10773 DRUG

BI 10773 tablets once daily high dose

BI 10773 Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients diagnosed with IGT according to the current ADA guidelines as a two-hour glucose levels of 140 to 199 mg/dl (7.8 mmol/l to 11.1 mmol/l) on the 75-g oral glucose tolerance test (OGTT), with an OGTT performed at the time of the screening visit (Visit 1), or
• ¿ Male and female patients diagnosed with type 2 diabetes mellitus (T2DM) prior to informed consent, on diet and exercise regimen who are drug-naïve, defined as absence of any oral antihyperglycemic therapy for 12 weeks prior starting with open-label active treatment, or
• Male and female patients diagnosed with type 2 diabetes mellitus prior to informed consent, who are pre-treated with metformin background therapy, on a stable dose of metformin of at least 1500 mg per day, unchanged for at least 12 weeks prior starting with open-label active treatment
• HbA1c at Visit 1 (screening)
• for patients diagnosed of IGT and for healthy subjects: HbA1c \< 6.5%
• for patients diagnosed of T2DM: HbA1c =6.5% and =10.5%
• Age = 18 at Visit 1
• BMI = 20 and = 40 Kg/m2 at Visit 1
• For patients with antihypertensive treatment, this must be stable (with no change in dosage) within 4 weeks prior starting with open-label active treatment
• Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation
• Males or females matching the below mentioned criteria and otherwise healthy according to the investigator¿s assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (BP, PR) and clinical laboratory tests .
• HbA1c at Visit 1 (screening): HbA1c \< 6.5%
• Confirmed normal glucose tolerance (NGT) by OGTT
• Age = 45 and = 55 at Visit 1.
• BMI = 30 and = 40 Kg/m2 (Body Mass Index) at Visit 1.

You may not qualify if:

• Acute coronary syndrome (non-STEMI \[ST elevation myocardial infarction\], STEMI, unstable AP \[angina pectoris\]), stroke or Transient Ischemic Attack (TIA) within 6 months prior to informed consent.
• Uncontrolled hyperglycaemia with a glucose level \> 240 mg/dl (\> 13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day).
• Indication of liver disease, defined by serum levels of either Alanine Aminotransferase (ALT \[SGPT\]), Aspartate Aminotransferase (AST \[SGOT\]), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run-in phase.
• Impaired renal function, defined as estimated Glomerular Filtration Rate (eGFR) \< 60 ml/min (moderate and severe renal impairment) as determined during screening and/or run-in phase.
• Medical history of insufficient bladder emptying (i.e. neurogenic bladder disorders).
• Patients with an Haemoglobin (Hb) \< 11.5 g/dl (for males) and Hb \< 10.5 g/dl (for females) at Visit 1.
• Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption within the last 5 years.
• Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.
• Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight.
• Alcohol or drug abuse (according to investigators judgment) within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake.
• Intake of an investigational drug in another trial Participation in another trial within 30 days prior to intake of study medication in this trial.
• Pre-menopausal women (last menstruation \< = 1 year prior to informed consent) who:
• Are nursing or pregnant or Are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial.
• Any other clinical condition that would jeopardize patients safety while participating in this clinical trial.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

1245.39.43001 Boehringer Ingelheim Investigational Site

Graz, Austria

Location

1245.39.49002 Boehringer Ingelheim Investigational Site

Neuss, Germany

Location

1245.39.39001 Boehringer Ingelheim Investigational Site

Pisa, Italy

Location

Related Publications (3)

• Ferrannini E, Baldi S, Frascerra S, Astiarraga B, Barsotti E, Clerico A, Muscelli E. Renal Handling of Ketones in Response to Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 2 Diabetes. Diabetes Care. 2017 Jun;40(6):771-776. doi: 10.2337/dc16-2724. Epub 2017 Mar 21.

  PMID: 28325783 DERIVED

• Muscelli E, Astiarraga B, Barsotti E, Mari A, Schliess F, Nosek L, Heise T, Broedl UC, Woerle HJ, Ferrannini E. Metabolic consequences of acute and chronic empagliflozin administration in treatment-naive and metformin pretreated patients with type 2 diabetes. Diabetologia. 2016 Apr;59(4):700-8. doi: 10.1007/s00125-015-3845-8. Epub 2015 Dec 24.

  PMID: 26704626 DERIVED

• Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, Broedl UC, Woerle HJ. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014 Feb;124(2):499-508. doi: 10.1172/JCI72227. Epub 2014 Jan 27.

  PMID: 24463454 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2010
• First Posted: November 25, 2010
• Study Start: November 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: September 9, 2014
• Results First Posted: September 9, 2014

Record last verified: 2014-08

Locations

DE (1); IT (1); AU (1)