Safety and Efficacy Study of Empagliflozin and Metformin for 24 Weeks in Treatment Naive Patients With Type 2 Diabetes

Tracking Information
First Submitted Date ICMJE	October 30, 2012
First Posted Date ICMJE	November 1, 2012
Results First Submitted Date	November 23, 2015
Results First Posted Date	February 19, 2016
Last Update Posted Date	February 19, 2016
Study Start Date ICMJE	October 2012
Actual Primary Completion Date	November 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 22, 2016)	HbA1c (Glycosylated Haemoglobin) Change From Baseline at Week 24 [ Time Frame: baseline and 24 weeks ]; Change from baseline in HbA1c (%) after 24 weeks of treatment. "Baseline" refers to the last observation before the start of any randomised trial treatment medication. Means presented are the adjusted means
Original Primary Outcome Measures ICMJE; (submitted: October 30, 2012)	Change from baseline in HbA1c [ Time Frame: 24 weeks ]
Change History	Complete list of historical versions of study NCT01719003 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 22, 2016)	FPG (Fasting Plasma Glucose) Change From Baseline at Week 24 [ Time Frame: baseline and 24 weeks ]Change from baseline in FPG (mg/dL) after 24 weeks of treatment. "Baseline" refers to the last observation before the start of any randomised trial treatment medication. Means presented are the adjusted means.; Body Weight Change From Baseline at Week 24 [ Time Frame: baseline and 24 weeks ]Change from baseline in body weight (kg) after 24 weeks of treatment. "Baseline" refers to the last observation before the start of any randomised trial treatment. medication. Means presented are the adjusted means.
Original Secondary Outcome Measures ICMJE; (submitted: October 30, 2012)	Change from baseline in fasting plasma glucose (FPG) [ Time Frame: 24 weeks ]; Change from baseline in body weight [ Time Frame: 24 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety and Efficacy Study of Empagliflozin and Metformin for 24 Weeks in Treatment Naive Patients With Type 2 Diabetes
Official Title ICMJE	A 24-week Phase III Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Twice Daily Oral Administration of Empagliflozin + Metformin Compared With the Individual Components of Empagliflozin or Metformin in Drug Naive Patients With Type 2 Diabetes Mellitus
Brief Summary	This study will investigate the efficacy and safety of two doses (high and low) of empagliflozin in combination with metformin (500 mg and 1000 mg) administered twice daily in patients with type 2 diabetes mellitus (T2DM). Study will compare four dose combinations of empagliflozin + metformin versus each individual component after 24 weeks of treatment.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
Condition ICMJE	Diabetes Mellitus, Type 2; Hyperglycemia
Intervention ICMJE	Drug: Metformin 500 mg bid Metformin 500 mg twice daily; Drug: Metformin 1000 mg bid Metformin 1000 mg twice daily; Drug: Empagliflozin low dose qd Empagliflozin low dose once daily; Drug: Empagliflozin high dose qd Empagliflozin high dose once daily; Drug: Empagliflozin low dose bid Empagliflozin low dose split twice daily; Drug: Empagliflozin high dose bid Empagliflozin high dose split twice daily
Study Arms	Experimental: Empagliflozin low dose qd Empagliflozin low dose once daily Intervention: Drug: Empagliflozin low dose qd; Experimental: Empagliflozin high dose qd Empagliflozin high dose once daily Intervention: Drug: Empagliflozin high dose qd; Experimental: OL empa high dose + met 1000 mg bid Open label empagliflozin high dose split twice daily + metformin 1000 mg twice daily - Patients are no longer enrolled into this arm because of change in the inclusion criteria in protocol version 2.0 all patients are now enrolled into remaining double-blind arms. Patients already enrolled in the open-label arm according to protocol version 1.0 can complete the study. Interventions: Drug: Metformin 1000 mg bid Drug: Empagliflozin high dose bid; Experimental: Empagliflozin low dose + met 500 mg bid Empagliflozin low dose split twice daily + metformin 500 mg twice daily Interventions: Drug: Metformin 500 mg bid Drug: Empagliflozin low dose bid; Experimental: Empagliflozin low dose + met 1000 mg bid Empagliflozin low dose split twice daily + metformin 1000 mg twice daily Interventions: Drug: Empagliflozin low dose bid Drug: Metformin 1000 mg bid; Experimental: Empagliflozin high dose + met 500 mg bid Empagliflozin high dose split twice daily + metformin 500 mg twice daily Interventions: Drug: Metformin 500 mg bid Drug: Empagliflozin high dose bid; Experimental: Empagliflozin high dose + met 1000mg bid Empagliflozin high dose split twice daily + metformin 1000 mg twice daily Interventions: Drug: Metformin 1000 mg bid Drug: Empagliflozin high dose bid; Experimental: Metformin 500 mg bid Metformin 500 mg twice daily Intervention: Drug: Metformin 500 mg bid; Experimental: Metformin 1000 mg bid Metformin 1000 mg twice daily Intervention: Drug: Metformin 1000 mg bid
Publications *	Hadjadj S, Rosenstock J, Meinicke T, Woerle HJ, Broedl UC. Initial Combination of Empagliflozin and Metformin in Patients With Type 2 Diabetes. Diabetes Care. 2016 Oct;39(10):1718-28. doi: 10.2337/dc16-0522. Epub 2016 Aug 4.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: January 22, 2016)	1413
Original Estimated Enrollment ICMJE; (submitted: October 30, 2012)	1424
Actual Study Completion Date	December 2014
Actual Primary Completion Date	November 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion criteria: Diagnosis of type 2 diabetes mellitus prior to informed consent; Male and female patients on diet and exercise regimen who are drug-naive, defined as absence of any oral antidiabetic therapy for 12 weeks prior to randomization; HbA1c >=7.5% and <= 12% (>=58.5 mmol/mol and <=107.7 mmol/mol); Body Mass Index (BMI) <= 45 kg/m2 at screening Exclusion criteria: Uncontrolled hyperglycemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second laboratory measurement (not on the same day); Any antidiabetic drug within 12 weeks prior to randomization; Impaired renal function, defined as estimated creatinine clearance rate (eCCr) <60 ml/min (Cockcroft-Gault formula) as determined during screening and/or run-in period; Contraindications to metformin according to the local label
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Brazil, Canada, Czech Republic, Egypt, France, Germany, Guatemala, Korea, Republic of, Lebanon, Malaysia, Mexico, Peru, Philippines, Russian Federation, Serbia, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Removed Location Countries	India, Indonesia, United Arab Emirates
Administrative Information
NCT Number ICMJE	NCT01719003
Other Study ID Numbers ICMJE	1276.1; 2010-021375-92 ( EudraCT Number: EudraCT )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Boehringer Ingelheim
Study Sponsor ICMJE	Boehringer Ingelheim
Collaborators ICMJE	Eli Lilly and Company
Investigators ICMJE	Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account	Boehringer Ingelheim
Verification Date	January 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP