Efficacy and Safety Study With Empagliflozin (BI 10773) vs. Placebo as add-on to Metformin or Metformin Plus Sulfonylurea Over 24 Weeks in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01159600
First received: July 8, 2010
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

The objective of the current study is to investigate the efficacy, safety and tolerability of two doses of BI 10773 compared to placebo given for 24 weeks as add-on therapy to metformin or metformin plus sulfonylurea in patients with Typ 2 Diabetes Mellitus with insufficient glycaemic control.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Placebo identical to BI 10773 high dose
Drug: Placebo identical to BI 10773 low dose
Drug: BI 10773
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase III Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of BI 10773 (10 mg, 25 mg) Administered Orally, Once Daily Over 24 Weeks in Patients With Type 2 Diabetes Mellitus With Insufficient Glycaemic Control Despite Treatment With Metformin Alone or Metformin in Combination With a Sulfonylurea

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • HbA1c Change From Baseline [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]

    Change from baseline in HbA1c after 24 weeks.

    For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication.



Secondary Outcome Measures:
  • Body Weight Change From Baseline [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]

    Body weight change from baseline after 24 weeks.

    For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication.


  • Mean Daily Plasma Glucose (MDG) Change From Baseline [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]

    Change from baseline in mean daily glucose (MDG) using the 8-point blood glucose profile, after 24 weeks of treatment.

    For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication.



Other Outcome Measures:
  • Confirmed Hypoglycaemic Adverse Events [ Time Frame: From first intake of randomised trial medication until 7 days after last trial medication intake, up to 231 days ] [ Designated as safety issue: No ]
    Number of patients with confirmed hypoglycaemic events, as reported as adverse events.


Enrollment: 1504
Study Start Date: July 2010
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 10773 Arm 2
BI 10773 once daily high dose
Drug: BI 10773
BI 10773 tablets once daily high dose
Drug: Placebo identical to BI 10773 low dose
Placebo tablets matching BI 10773 low dose
Placebo Comparator: Placebo
Placebo matching BI 10773
Drug: Placebo identical to BI 10773 low dose
Placebo tablets matching BI 10773 low dose
Drug: Placebo identical to BI 10773 high dose
Placebo tablets matching BI 10773 high dose
Experimental: BI 10773 open-label
BI 10773 once daily high dose open label
Drug: BI 10773
BI 10773 tablets once daily high dose open label
Experimental: BI 10773 Arm 1
BI 10773 once daily low dose
Drug: Placebo identical to BI 10773 high dose
Placebo tablets matching BI 10773 high dose
Drug: BI 10773
BI 10773 tablets once daily low dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Diagnosis of type 2 diabetes mellitus prior to informed consent
  2. Male and female patients on a diet and exercise regimen who are pre-treated with immediate release metformin or immediate release metformin plus sulfonylurea (see below for minimum doses). The treatment regimen has to be unchanged for 12 weeks prior to randomisation.

    Minimum dose for metformin: > or = 1500 mg/day or maximum tolerated dose or maximum dose according to local label Minimum dose for sulfonylurea: > or = half of the maximal recommended dose or maximum tolerated dose or maximum dose according to local label

  3. HbA1c of > or = 7.0% and < or = 11% at Visit 1 (screening) in order to be eligible for randomised treatment HbA1c of > 11% at Visit 1 (screening) in order to be eligible for the open-label treatment arm (25 mg BI 10773)
  4. Age> or = 18
  5. Body Mass Index (BM)I < or = 45 kg/m2 (Body Mass Index) at Visit 1 (Screening)
  6. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

  1. 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)
  2. Any other antidiabetic drug within 12 weeks prior to randomisation except those mentioned in inclusion criterion 2
  3. Myocardial infarction, stroke or transient ischemic attack (TIA) within 3 months prior to informed consent
  4. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run-in phase
  5. Impaired renal function, defined as eGFR<30 ml/min (severe renal impairment) as determined during screening and/or run-in phase
  6. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
  7. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
  8. Contraindications to metformin and/or sulfonylurea according to the local label for those patients that enter the study with the respective background therapy
  9. Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anaemia)
  10. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 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
  11. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except Typ 2 Diabetes
  12. 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. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner
  13. Alcohol or drug abuse 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
  14. Participation in another trial with an investigational drug within 30 days prior to informed consent
  15. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial
  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: NCT01159600

  Show 148 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
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: NCT01159600     History of Changes
Other Study ID Numbers: 1245.23, 2009-016258-41
Study First Received: July 8, 2010
Results First Received: May 16, 2014
Last Updated: May 16, 2014
Health Authority: Canada: Health Canada
China: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
India: Drugs Controller General of India
Korea: Food and Drug Administration
Mexico: Federal Commission for Sanitary Risks Protection
Slovakia: State Institute for Drug Control
Slovenia: Agency for Medicinal Products - Ministry of Health
Taiwan : Food and Drug Administration
Turkey: Ministry of Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 02, 2014