Safety and Efficacy Study of Empagliflozin and Metformin... | NCT01719003

NCT01719003

ID	Type	Description	Link
2010-021375-92	EudraCT Number	EudraCT

Status Module

Sponsor/Collaborators Module

Name	Class
Eli Lilly and Company	INDUSTRY

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Empagliflozin low dose qd	Experimental	Empagliflozin low dose once daily	Drug: Empagliflozin low dose qd
Empagliflozin high dose qd	Experimental	Empagliflozin high dose once daily	Drug: Empagliflozin high dose qd
OL empa high dose + met 1000 mg bid	Experimental	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.	Drug: Metformin 1000 mg bid Drug: Empagliflozin high dose bid
Empagliflozin low dose + met 500 mg bid	Experimental	Empagliflozin low dose split twice daily + metformin 500 mg twice daily	Drug: Metformin 500 mg bid Drug: Empagliflozin low dose bid
Empagliflozin low dose + met 1000 mg bid	Experimental	Empagliflozin low dose split twice daily + metformin 1000 mg twice daily

Name	Type	Description	Arm Group Labels	Other Names
Metformin 500 mg bid	Drug	Metformin 500 mg twice daily	Empagliflozin low dose + met 500 mg bid

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
HbA1c (Glycosylated Haemoglobin) Change From Baseline at Week 24	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	baseline and 24 weeks

Secondary Outcomes

Measure	Description	Time Frame
FPG (Fasting Plasma Glucose) Change From Baseline at Week 24	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.	baseline and 24 weeks
Body Weight Change From Baseline at Week 24

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1276.1.10014 Boehringer Ingelheim Investigational Site		Birmingham	Alabama		United States
1276.1.10019 Boehringer Ingelheim Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27493136	Derived	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.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid	Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)
FG001	Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid

Full analysis set (FAS): FAS comprised all randomised patients treated with at least 1 dose of trial medication, with a baseline and at least 1 on-treatment HbA1c assessment.

Arm/Group Information

ID	Title	Description
BG000	Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid	Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)
BG001	Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid	Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid
BG002	Empagliflozin 5 mg Bid + Metformin 1000 mg Bid	Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid
BG003	Empagliflozin 5 mg Bid + Metformin 500 mg Bid	Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid
BG004	Empagliflozin 25 mg qd	Oral administration of Empagliflozin 25 mg once daily (qd)
BG005	Empagliflozin 10 mg qd	Oral administration of Empagliflozin 10 mg qd
BG006	Metformin 1000 mg Bid	Oral administration of Metformin 1000 mg bid
BG007	Metformin 500 mg Bid	Oral administration of Metformin 500 mg bid
BG008	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-2.08± 0.08 OG001-1.93± 0.08 OG002-2.07± 0.08 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG006	Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach comparing the change from baseline of HbA1c (in units of %) after 24 weeks of double-blind treatment.	Mixed Models Analysis	'Baseline HbA1c':linear covariate;'treatment','baseline renal function','region','visit' & 'visit by treatment interaction':fixed effects.	0.0056		Adjusted mean	-0.33	Standard Error of the Mean	0.12	2-Sided	95	-0.56	-0.10			Empagliflozin 12.5 mg bid+ Metformin 1000 mg bid minus Metformin 1000 mg bid	No

Secondary

FPG (Fasting Plasma Glucose) Change From Baseline at Week 24

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.

FAS observed cases (OC) (Only patients with available data are analysed)

Posted

Mean

Standard Error

mg/dL

baseline and 24 weeks

ID	Title	Description
OG000	Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid	Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)
OG001	Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid	Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid
OG002	Empagliflozin 5 mg Bid + Metformin 1000 mg Bid	Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid
OG003	Empagliflozin 5 mg Bid + Metformin 500 mg Bid	Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid

Secondary

Body Weight Change From Baseline at Week 24

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.

FAS observed cases (OC) (Only patients with available data are analysed)

Posted

Mean

Standard Error

baseline and 24 weeks

ID	Title	Description
OG000	Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid	Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)
OG001	Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid	Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid
OG002	Empagliflozin 5 mg Bid + Metformin 1000 mg Bid	Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid
OG003	Empagliflozin 5 mg Bid + Metformin 500 mg Bid	Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid	Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)	2	170	48	170
EG001	Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid	Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid	6	170	40	170
EG002	Empagliflozin 5 mg Bid + Metformin 1000 mg Bid	Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid	3	171	35	171
EG003	Empagliflozin 5 mg Bid + Metformin 500 mg Bid	Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid	2	169	42	169
EG004	Empagliflozin 25 mg qd	Oral administration of Empagliflozin 25 mg once daily (qd)	3	167	41	167
EG005	Empagliflozin 10 mg qd	Oral administration of Empagliflozin 10 mg qd	1	172	36	172
EG006	Metformin 1000 mg Bid	Oral administration of Metformin 1000 mg bid	3	170	53	170
EG007	Metformin 500 mg Bid	Oral administration of Metformin 500 mg bid	3	171	38	171
EG008	Empagliflozin 12.5 mg Bid + Metformin 1000 mg Bid OL	Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg bid in an open label (OL)	2	53	16	53

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0021 affected171 at risk EG0030 affected169 at risk EG0040 affected167 at risk EG0050 affected172 at risk EG0060 affected170 at risk EG0070 affected171 at risk EG0080 affected53 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Tachycardia paroxysmal	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0011 affected170 at risk EG0020 affected171 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0011 affected170 at risk EG0020 affected171 at risk EG003
Chest pain	General disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Cholangitis acute	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0011 affected170 at risk EG0020 affected171 at risk EG003
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0011 affected170 at risk EG0020 affected171 at risk EG003
Appendicitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0011 affected170 at risk EG0020 affected171 at risk EG003
Dengue fever	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Herpes simplex encephalitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Nasal abscess	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0011 affected170 at risk EG0020 affected171 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0021 affected171 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0021 affected171 at risk EG003
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Chronic lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0011 affected170 at risk EG0020 affected171 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0001 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Cerebral infarction	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0011 affected170 at risk EG0020 affected171 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0010 affected170 at risk EG0020 affected171 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG00012 affected170 at risk EG0016 affected170 at risk EG0025 affected171 at risk EG0039 affected169 at risk EG0046 affected167 at risk EG0052 affected172 at risk EG00624 affected170 at risk EG0076 affected171 at risk EG0084 affected53 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0004 affected170 at risk EG0015 affected170 at risk EG0028 affected171 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG00018 affected170 at risk EG00117 affected170 at risk EG00212 affected171 at risk EG003
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0008 affected170 at risk EG0016 affected170 at risk EG0028 affected171 at risk EG003
Dizziness	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0006 affected170 at risk EG0019 affected170 at risk EG0024 affected171 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected170 at risk EG0011 affected170 at risk EG0022 affected171 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0006 affected170 at risk EG0014 affected170 at risk EG0025 affected171 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0004 affected170 at risk EG0014 affected170 at risk EG0021 affected171 at risk EG003

ID	Term
D003924	Diabetes Mellitus, Type 2
D006943	Hyperglycemia

ID	Term
D008687	Metformin
C494814	BID protein, human
C570240	empagliflozin

Superiority or Other

EG0040 affected167 at risk

EG0051 affected172 at risk

EG0060 affected170 at risk

EG0071 affected171 at risk

EG0081 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0081 affected53 at risk

EG0041 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0041 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0041 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0071 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0071 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0061 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0061 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0041 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0061 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0041 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0080 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0081 affected53 at risk

EG0040 affected167 at risk

EG0050 affected172 at risk

EG0060 affected170 at risk

EG0070 affected171 at risk

EG0081 affected53 at risk

EG0047 affected167 at risk

EG0055 affected172 at risk

EG0065 affected170 at risk

EG00710 affected171 at risk

EG0083 affected53 at risk

EG00413 affected167 at risk

EG00512 affected172 at risk

EG00614 affected170 at risk

EG00712 affected171 at risk

EG0080 affected53 at risk

EG00411 affected167 at risk

EG00515 affected172 at risk

EG0068 affected170 at risk

EG0077 affected171 at risk

EG0082 affected53 at risk

EG0043 affected167 at risk

EG0054 affected172 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals