Efficacy and Safety of Empagliflozin (BI 10773) in Type 2 Diabetes Patients on a Background of Pioglitazone Alone or With Metformin

NCT01210001 | Completed Phase 3 Results

• 2 other identifiers: 1245.192009-016154-40
• Study Type: interventional
• Target: 499
• Locations: 7 countries
• Sites: 68

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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (2)

• HbA1c Change From Baseline

  Change From Baseline in HbA1c after 24 weeks. Note that adjusted means are provided.

  Baseline and 24 weeks

• HbA1c Change From Baseline for Pio and Met Background Medication Patients

  Change From Baseline in HbA1c after 24 weeks for patients with pioglitazone (pio) and metformin (met) background medication only. Note that adjusted means are provided.

  Baseline and 24 weeks

Secondary Outcomes (2)

• Fasting Plasma Glucose (FPG) Change From Baseline

  Baseline and 24 weeks

• Body Weight Change From Baseline

  Baseline and 24 weeks

Other Outcomes (1)

• Hypoglycaemic Events

  From first drug administration until 7 days after last intake of study drug, up to 256 days

Study Arms (3)

BI 10773 low dose

EXPERIMENTAL

BI 10773 tablets once daily

Drug: BI 10773; Drug: Placebo

BI 10773 high dose

EXPERIMENTAL

BI 10773 tablets once daily

Drug: Placebo; Drug: BI 10773

Placebo

PLACEBO COMPARATOR

Placebo tablets matching BI 10773

Drug: Placebo

Interventions

Placebo DRUG

Placebo tablets matching BI 10773 low dose

Placebo

BI 10773 DRUG

BI 10773 tablets once daily

BI 10773 low dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of type 2 diabetes mellitus prior to informed consent.
• 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.
• HbA1c of \>/= 7.0% and \</= 10.0% at Visit 1 (screening).
• Age \>/= 18.
• BMI \</= 45 kg/m2 (Body Mass Index) at Visit 1 (screening).
• Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation.

You may not qualify if:

• 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).
• Myocardial infarction, stroke or transient ischaemic attack (TIA) within 3 months prior to informed consent.
• 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).
• 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).
• Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
• Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years .
• Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g. malaria, babesiosis, haemolytic anaemia).
• Contraindications to pioglitazone according to the local label.
• 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.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (68)

1245.19.10056 Boehringer Ingelheim Investigational Site

Muscle Shoals, Alabama, United States

Location

1245.19.10162 Boehringer Ingelheim Investigational Site

Glendale, Arizona, United States

Location

1245.19.10161 Boehringer Ingelheim Investigational Site

Phoenix, Arizona, United States

Location

1245.19.10046 Boehringer Ingelheim Investigational Site

Tempe, Arizona, United States

Location

1245.19.10070 Boehringer Ingelheim Investigational Site

Irvine, California, United States

Location

1245.19.10047 Boehringer Ingelheim Investigational Site

La Mesa, California, United States

Location

1245.19.10149 Boehringer Ingelheim Investigational Site

Rancho Cucamonga, California, United States

Location

1245.19.10163 Boehringer Ingelheim Investigational Site

Riverside, California, United States

Location

1245.19.10131 Boehringer Ingelheim Investigational Site

West Hills, California, United States

Location

1245.19.10141 Boehringer Ingelheim Investigational Site

Milford, Connecticut, United States

Location

1245.19.10133 Boehringer Ingelheim Investigational Site

Jupiter, Florida, United States

Location

1245.19.10085 Boehringer Ingelheim Investigational Site

Plantation, Florida, United States

Location

1245.19.10077 Boehringer Ingelheim Investigational Site

Perry, Georgia, United States

Location

1245.19.10014 Boehringer Ingelheim Investigational Site

Dubuque, Iowa, United States

Location

1245.19.10160 Boehringer Ingelheim Investigational Site

Essex, Maryland, United States

Location

1245.19.10003 Boehringer Ingelheim Investigational Site

Dearborn, Michigan, United States

Location

1245.19.10059 Boehringer Ingelheim Investigational Site

New Hyde Park, New York, United States

Location

1245.19.10123 Boehringer Ingelheim Investigational Site

Smithtown, New York, United States

Location

1245.19.10071 Boehringer Ingelheim Investigational Site

Asheboro, North Carolina, United States

Location

1245.19.10086 Boehringer Ingelheim Investigational Site

Salisbury, North Carolina, United States

Location

1245.19.10008 Boehringer Ingelheim Investigational Site

Marion, Ohio, United States

Location

1245.19.10033 Boehringer Ingelheim Investigational Site

Chattanooga, Tennessee, United States

Location

1245.19.10112 Boehringer Ingelheim Investigational Site

Memphis, Tennessee, United States

Location

1245.19.10002 Boehringer Ingelheim Investigational Site

Norfolk, Virginia, United States

Location

1245.19.20047 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1245.19.20062 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1245.19.20012 G.A. Research Associates Ltd.

Moncton, New Brunswick, Canada

Location

1245.19.20031 Boehringer Ingelheim Investigational Site

St. John's, Newfoundland and Labrador, Canada

Location

1245.19.20057 Boehringer Ingelheim Investigational Site

Brampton, Ontario, Canada

Location

1245.19.20059 Boehringer Ingelheim Investigational Site

Fort Erie, Ontario, Canada

Location

1245.19.20060 Boehringer Ingelheim Investigational Site

London, Ontario, Canada

Location

1245.19.20009 Boehringer Ingelheim Investigational Site

Newmarket, Ontario, Canada

Location

1245.19.20034 Boehringer Ingelheim Investigational Site

Sarnia, Ontario, Canada

Location

1245.19.20058 Boehringer Ingelheim Investigational Site

Saint Romuald, Quebec, Canada

Location

1245.19.20041 Boehringer Ingelheim Investigational Site

Saskatoon, Saskatchewan, Canada

Location

1245.19.30002 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

1245.19.30001 Boehringer Ingelheim Investigational Site

Nikaia, Greece

Location

1245.19.30004 Boehringer Ingelheim Investigational Site

Thessaloniki, Greece

Location

1245.19.91005 Boehringer Ingelheim Investigational Site

Bangalore, India

Location

1245.19.91006 Boehringer Ingelheim Investigational Site

Bangalore, India

Location

1245.19.91008 Boehringer Ingelheim Investigational Site

Bangalore, India

Location

1245.19.91003 Boehringer Ingelheim Investigational Site

Belagavi, India

Location

1245.19.91004 Boehringer Ingelheim Investigational Site

Chennai, India

Location

1245.19.91009 Boehringer Ingelheim Investigational Site

Chennai, India

Location

1245.19.91001 Boehringer Ingelheim Investigational Site

Coimbatore, India

Location

1245.19.91015 Boehringer Ingelheim Investigational Site

Kalaburagi, India

Location

1245.19.91011 Boehringer Ingelheim Investigational Site

Kartanaka, India

Location

1245.19.91002 Boehringer Ingelheim Investigational Site

Mumbai, India

Location

1245.19.91007 Boehringer Ingelheim Investigational Site

Mumbai, Maharastra, India

Location

1245.19.91017 Boehringer Ingelheim Investigational Site

Mysore, India

Location

1245.19.91010 Boehringer Ingelheim Investigational Site

Nagpur, India

Location

1245.19.91012 Boehringer Ingelheim Investigational Site

New Delhi, India

Location

1245.19.91013 Boehringer Ingelheim Investigational Site

Patna, India

Location

1245.19.91014 Boehringer Ingelheim Investigational Site

Pune, India

Location

1245.19.91016 Boehringer Ingelheim Investigational Site

Pune, India

Location

1245.19.63002 Boehringer Ingelheim Investigational Site

Cebu City, N/A, Philippines, Philippines

Location

1245.19.63003 Boehringer Ingelheim Investigational Site

Davao City, N/A, Philippines, Philippines

Location

1245.19.63004 Boehringer Ingelheim Investigational Site

Manila, Philippines, Philippines

Location

1245.19.63005 Boehringer Ingelheim Investigational Site

Pasig City, Philippines, Philippines

Location

1245.19.63001 Boehringer Ingelheim Investigational Site

San Juan City, Philippines, Philippines

Location

1245.19.66003 Boehringer Ingelheim Investigational Site

Saimai, Thailand

Location

1245.19.66004 Boehringer Ingelheim Investigational Site

Udon Thani, Thailand, Thailand

Location

1245.19.75002 Boehringer Ingelheim Investigational Site

Dnipro, Ukraine

Location

1245.19.75001 Boehringer Ingelheim Investigational Site

Kharkiv, Ukraine

Location

1245.19.75005 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

1245.19.75006 Boehringer Ingelheim Investigational Site

Lviv, Ukraine

Location

1245.19.75004 Boehringer Ingelheim Investigational Site

Vinnitsa, Ukraine

Location

1245.19.75003 Boehringer Ingelheim Investigational Site

Vinnytsia, Ukraine

Location

Related Publications (4)

• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

  PMID: 38770818 DERIVED

• 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.

  PMID: 35472672 DERIVED

• 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.

  PMID: 27316632 DERIVED

• 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.

  PMID: 26138864 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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2010
• First Posted: September 28, 2010
• Study Start: September 1, 2010
• Primary Completion: April 1, 2012
• Last Updated: June 17, 2014
• Results First Posted: June 17, 2014

Record last verified: 2014-05

Locations

GR (3); IN (17); TH (2); CA (11); PH (5); UA (6); US (24)