Clinical trial NCT01210001: Efficacy and Safety of Empagliflozin (BI 10773) in Type 2 Diabetes Patients on a Background of Pioglitazone Alone or With Metformin
Official title: A Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Trial of BI 10773 (10 and 25 mg Administered Orally Once Daily) Over 24 Weeks in Patients With Type 2 Diabetes Mellitus With Insufficient Glycaemic Control Despite a Background Therapy of Pioglitazone Alone or in Combination With Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2010-09-28
Enrollment: 499
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will investigate the efficacy and safety of BI 10773 in type 2 diabetic patients in order to provide these data for approval for BI 10773 by regulatory authorities as an antidiabetic agent as add-on therapy to pioglitazone alone or in combination with metformin.


Eligibility criteria: Inclusion criteria:

1. Diagnosis of type 2 diabetes mellitus prior to informed consent.
2. Male and female patients on diet and exercise regimen who are pre-treated with pioglitazone alone or in combination with metformin. The treatment regimen should be unchanged for 12 weeks prior to randomisation.
3. HbA1c of \>/= 7.0% and \</= 10.0% at Visit 1 (screening).
4. Age \>/= 18.
5. BMI \</= 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 medication within 12 weeks prior to randomisation, except those defined as the permitted background therapy via inclusion criteria no. 2.
3. Myocardial infarction, stroke or transient ischaemic attack (TIA) within 3 months prior to informed consent.
4. Indication of liver disease, defined by serum levels of either alanine transaminase (ALT/SGPT), aspartate transaminase (AST/SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening or during the placebo run-in period (i.e. at a visit prior to the randomisation visit, Visit 3).
5. Impaired renal function, defined as eGFR (estimated Glomerular Filtration Rate) \< 30 ml/min (severe renal impairment, MDRD \[Modification of Diet in Renal Disease\] formula) as determined during screening or during the placebo run-in period (i.e. at a visit prior to the randomisation visit, Visit 3).
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. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g. malaria, babesiosis, haemolytic anaemia).
9. Contraindications to pioglitazone according to the local label.
10. Contraindication to pioglitazone and/or metformin (relevant only for those patients who enter the study with both these background therapies) according to the local labels.
11. 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.
12. 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 T2D.
13. 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 trial 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 to local authorities), double barrier method and vasectomised partner.
14. 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.
15. Participation in another trial with an investigational drug within 30 days prior to informed consent.
16. Any other clinical condition that would jeopardise patient safety while participating in this clinical trial.

Primary outcomes:
measure: HbA1c Change From Baseline
timeFrame: Baseline and 24 weeks
measure: HbA1c Change From Baseline for Pio and Met Background Medication Patients
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: Fasting Plasma Glucose (FPG) Change From Baseline
timeFrame: Baseline and 24 weeks
measure: Body Weight Change From Baseline
timeFrame: Baseline and 24 weeks
Other outcomes:
measure: Hypoglycaemic Events
timeFrame: From first drug administration until 7 days after last intake of study drug, up to 256 days
Locations:
city: Muscle Shoals
country: United States
facility: 1245.19.10056 Boehringer Ingelheim Investigational Site
state: Alabama
city: Glendale
country: United States
facility: 1245.19.10162 Boehringer Ingelheim Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: 1245.19.10161 Boehringer Ingelheim Investigational Site
state: Arizona
city: Tempe
country: United States
facility: 1245.19.10046 Boehringer Ingelheim Investigational Site
state: Arizona
city: Irvine
country: United States
facility: 1245.19.10070 Boehringer Ingelheim Investigational Site
state: California
city: La Mesa
country: United States
facility: 1245.19.10047 Boehringer Ingelheim Investigational Site
state: California
city: Rancho Cucamonga
country: United States
facility: 1245.19.10149 Boehringer Ingelheim Investigational Site
state: California
city: Riverside
country: United States
facility: 1245.19.10163 Boehringer Ingelheim Investigational Site
state: California
city: West Hills
country: United States
facility: 1245.19.10131 Boehringer Ingelheim Investigational Site
state: California
city: Milford
country: United States
facility: 1245.19.10141 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Jupiter
country: United States
facility: 1245.19.10133 Boehringer Ingelheim Investigational Site
state: Florida
city: Plantation
country: United States
facility: 1245.19.10085 Boehringer Ingelheim Investigational Site
state: Florida
city: Perry
country: United States
facility: 1245.19.10077 Boehringer Ingelheim Investigational Site
state: Georgia
city: Dubuque
country: United States
facility: 1245.19.10014 Boehringer Ingelheim Investigational Site
state: Iowa
city: Essex
country: United States
facility: 1245.19.10160 Boehringer Ingelheim Investigational Site
state: Maryland
city: Dearborn
country: United States
facility: 1245.19.10003 Boehringer Ingelheim Investigational Site
state: Michigan
city: New Hyde Park
country: United States
facility: 1245.19.10059 Boehringer Ingelheim Investigational Site
state: New York
city: Smithtown
country: United States
facility: 1245.19.10123 Boehringer Ingelheim Investigational Site
state: New York
city: Asheboro
country: United States
facility: 1245.19.10071 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Salisbury
country: United States
facility: 1245.19.10086 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Marion
country: United States
facility: 1245.19.10008 Boehringer Ingelheim Investigational Site
state: Ohio
city: Chattanooga
country: United States
facility: 1245.19.10033 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Memphis
country: United States
facility: 1245.19.10112 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Norfolk
country: United States
facility: 1245.19.10002 Boehringer Ingelheim Investigational Site
state: Virginia
city: Vancouver
country: Canada
facility: 1245.19.20047 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1245.19.20062 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Moncton
country: Canada
facility: 1245.19.20012 G.A. Research Associates Ltd.
state: New Brunswick
city: St. John's
country: Canada
facility: 1245.19.20031 Boehringer Ingelheim Investigational Site
state: Newfoundland and Labrador
city: Brampton
country: Canada
facility: 1245.19.20057 Boehringer Ingelheim Investigational Site
state: Ontario
city: Fort Erie
country: Canada
facility: 1245.19.20059 Boehringer Ingelheim Investigational Site
state: Ontario
city: London
country: Canada
facility: 1245.19.20060 Boehringer Ingelheim Investigational Site
state: Ontario
city: Newmarket
country: Canada
facility: 1245.19.20009 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: 1245.19.20034 Boehringer Ingelheim Investigational Site
state: Ontario
city: St-Romuald
country: Canada
facility: 1245.19.20058 Boehringer Ingelheim Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: 1245.19.20041 Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Athens
country: Greece
facility: 1245.19.30002 Boehringer Ingelheim Investigational Site
city: Nikaia
country: Greece
facility: 1245.19.30001 Boehringer Ingelheim Investigational Site
city: Thessaloniki
country: Greece
facility: 1245.19.30004 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1245.19.91005 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1245.19.91006 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 1245.19.91008 Boehringer Ingelheim Investigational Site
city: Belgaum
country: India
facility: 1245.19.91003 Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: 1245.19.91004 Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: 1245.19.91009 Boehringer Ingelheim Investigational Site
city: Coimbatore
country: India
facility: 1245.19.91001 Boehringer Ingelheim Investigational Site
city: Gulbarga
country: India
facility: 1245.19.91015 Boehringer Ingelheim Investigational Site
city: Kartanaka
country: India
facility: 1245.19.91011 Boehringer Ingelheim Investigational Site
city: Mumbai, Maharastra
country: India
facility: 1245.19.91007 Boehringer Ingelheim Investigational Site
city: Mumbai
country: India
facility: 1245.19.91002 Boehringer Ingelheim Investigational Site
city: Mysore
country: India
facility: 1245.19.91017 Boehringer Ingelheim Investigational Site
city: Nagpur
country: India
facility: 1245.19.91010 Boehringer Ingelheim Investigational Site
city: New Delhi
country: India
facility: 1245.19.91012 Boehringer Ingelheim Investigational Site
city: Patna
country: India
facility: 1245.19.91013 Boehringer Ingelheim Investigational Site
city: Pune
country: India
facility: 1245.19.91014 Boehringer Ingelheim Investigational Site
city: Pune
country: India
facility: 1245.19.91016 Boehringer Ingelheim Investigational Site
city: Cebu City, N/A, Philippines
country: Philippines
facility: 1245.19.63002 Boehringer Ingelheim Investigational Site
city: Davao City, N/A, Philippines
country: Philippines
facility: 1245.19.63003 Boehringer Ingelheim Investigational Site
city: Manila, Philippines
country: Philippines
facility: 1245.19.63004 Boehringer Ingelheim Investigational Site
city: Pasig City, Philippines
country: Philippines
facility: 1245.19.63005 Boehringer Ingelheim Investigational Site
city: San Juan City, Philippines
country: Philippines
facility: 1245.19.63001 Boehringer Ingelheim Investigational Site
city: Saimai
country: Thailand
facility: 1245.19.66003 Boehringer Ingelheim Investigational Site
city: Udon Thani, Thailand
country: Thailand
facility: 1245.19.66004 Boehringer Ingelheim Investigational Site
city: Dnepropetrovsk
country: Ukraine
facility: 1245.19.75002 Boehringer Ingelheim Investigational Site
city: Kharkov
country: Ukraine
facility: 1245.19.75001 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 1245.19.75005 Boehringer Ingelheim Investigational Site
city: Lviv
country: Ukraine
facility: 1245.19.75006 Boehringer Ingelheim Investigational Site
city: Vinnitsa
country: Ukraine
facility: 1245.19.75004 Boehringer Ingelheim Investigational Site
city: Vinnytsya
country: Ukraine
facility: 1245.19.75003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.
citation: Cherney D, Lund SS, Perkins BA, Groop PH, Cooper ME, Kaspers S, Pfarr E, Woerle HJ, von Eynatten M. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia. 2016 Sep;59(9):1860-70. doi: 10.1007/s00125-016-4008-2. Epub 2016 Jun 17.
citation: Kovacs CS, Seshiah V, Merker L, Christiansen AV, Roux F, Salsali A, Kim G, Stella P, Woerle HJ, Broedl UC; EMPA-REG EXTEND PIO investigators. Empagliflozin as Add-on Therapy to Pioglitazone With or Without Metformin in Patients With Type 2 Diabetes Mellitus. Clin Ther. 2015 Aug;37(8):1773-88.e1. doi: 10.1016/j.clinthera.2015.05.511. Epub 2015 Jun 29.