A 16 Weeks Study on Efficacy and Safety of Two Doses of E... | NCT01649297

ID	Type	Description	Link
2012-000905-53	EudraCT Number	EudraCT

Name	Class
Eli Lilly and Company	INDUSTRY

A 16 Weeks Study on Efficacy and Safety of Two Doses of E... | NCT01649297 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
empagliflozin (high dose qd)	Experimental	Patients receive Empagliflozin high dose once daily	Drug: Placebo Drug: Empagliflozin (high dose qd)
empagliflozin (high dose bid)	Experimental	Patients receive Empagliflozin high dose split twice daily	Drug: Placebo Drug: empagliflozin (high dose bid)
empagliflozin (low dose qd)	Experimental	Patients receive Empagliflozin low dose once daily	Drug: empagliflozin (low dose qd) Drug: Placebo
empagliflozin (low dose bid)	Experimental	Patients receive Empagliflozin low dose split twice daily	Drug: Placebo Drug: empagliflozin (low dose bid)
Placebo	Placebo Comparator	Patients receive placebo matching Empagliflozin	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Patients receive placebo matching empagliflozin (low dose qd)	empagliflozin (high dose qd)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
HbA1c (Glycosylated Haemoglobin) Change From Baseline at Week 16	Change from baseline in HbA1c (%) after 16 weeks of treatment. The term 'baseline' refers to the last observation prior to the first intake of any randomised study medication. Means provided are the adjusted means.	Baseline and 16 weeks

Secondary Outcomes

Measure	Description	Time Frame
Fasting Plasma Glucose (FPG) Change From Baseline at Week 16	Change from baseline in FPG (mg/dL) after 16 weeks of treatment. The term 'baseline' refers to the last observation prior to the first intake of any randomised study medication. Means provided are the adjusted means.	Baseline and 16 weeks

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1276.10.11036 Boehringer Ingelheim Investigational Site		Florence	Alabama		United States
1276.10.11049 Boehringer Ingelheim Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35472672	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.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Empa 12.5mg BID	Oral administration of Empagliflozin (Empa) 12.5 mg twice daily (BID)
FG001	Empa 25mg QD	Oral administration of Empagliflozin (Empa) 25 mg once daily (QD)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Adverse Event		FG0005 subjects FG0015 subjects FG0024 subjects FG00313 subjects FG0041 subjects
Lack of Efficacy		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
Non compliant with Protocol		FG0001 subjects FG0010 subjects FG0023 subjects FG0032 subjects FG004
Lost to Follow-up		FG0001 subjects FG0011 subjects FG0024 subjects FG0033 subjects FG004
Patient withdrawal (not due to AE)		FG0003 subjects FG0016 subjects FG0024 subjects FG0031 subjects FG004
For other reason		FG0004 subjects FG0011 subjects FG0022 subjects FG0030 subjects FG004

Arm/Group Information

ID	Title	Description
BG000	Empa 12.5mg BID	Oral administration of Empagliflozin (Empa) 12.5 mg twice daily (BID)
BG001	Empa 25mg QD	Oral administration of Empagliflozin (Empa) 25 mg once daily (QD)
BG002	Empa 5mg BID	Oral administration of Empagliflozin (Empa) 5 mg twice daily (BID)
BG003	Empa 10mg QD	Oral administration of Empagliflozin (Empa) 10 mg once daily (QD)
BG004	Placebo	Oral administration of Placebo tablets matching empagliflozin 25 mg, 10 mg, 5 mg, and 2.5 mg
BG005	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
	OG000-0.83± 0.05 OG001-0.72± 0.05 OG002-0.66± 0.05 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
OG002 OG003	The primary objective was to test the non-inferiority of empagliflozin 5 mg BID versus empagliflozin 10 mg QD, and non-inferiority of empagliflozin 12.5 mg BID versus empagliflozin 25 mg QD, assuming a non-inferiority margin of 0.35%	ANCOVA	ANCOVA: Treatment, geographical region, renal function (screening eGFR [MDRD] value)- fixed effects and baseline HbA1c- linear covariate.	<0.0001	The two non-inferiority hypotheses H10 and H20 were tested using the Hochberg procedure in order to control the family-wise type I error at 0.025 (one-sided).	Adjusted mean difference	-0.02	Standard Error of the Mean	0.07		95	-0.16	0.13				Yes

Secondary

Fasting Plasma Glucose (FPG) Change From Baseline at Week 16

Change from baseline in FPG (mg/dL) after 16 weeks of treatment. The term 'baseline' refers to the last observation prior to the first intake of any randomised study medication.

Means provided are the adjusted means.

FAS with LOCF has been used for FPG analyses

Posted

Mean

Standard Error

mg/dL

Baseline and 16 weeks

ID	Title	Description
OG000	Empa 12.5mg BID	Oral administration of Empagliflozin (Empa) 12.5 mg twice daily (BID)
OG001	Empa 25mg QD	Oral administration of Empagliflozin (Empa) 25 mg once daily (QD)
OG002	Empa 5mg BID	Oral administration of Empagliflozin (Empa) 5 mg twice daily (BID)
OG003	Empa 10mg QD	Oral administration of Empagliflozin (Empa) 10 mg once daily (QD)
OG004	Placebo

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Empa 12.5mg BID	Oral administration of Empagliflozin (Empa) 12.5 mg twice daily (BID)	5	219	10	219
EG001	Empa 25mg QD	Oral administration of Empagliflozin (Empa) 25 mg once daily (QD)	2	218	10	218
EG002	Empa 5mg BID	Oral administration of Empagliflozin (Empa) 5 mg twice daily (BID)	7	219	8	219
EG003	Empa 10mg QD	Oral administration of Empagliflozin (Empa) 10 mg once daily (QD)	5	220	15	220
EG004	Placebo	Oral administration of Placebo tablets matching empagliflozin 25 mg, 10 mg, 5 mg, and 2.5 mg	1	107	4	107

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diverticulitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0011 affected218 at risk EG0020 affected219 at risk EG0030 affected220 at risk EG0040 affected107 at risk
Pharyngotonsillitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0021 affected219 at risk EG003
Biliary adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0021 affected219 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0001 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Macular degeneration	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0011 affected218 at risk EG0020 affected219 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0021 affected219 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0021 affected219 at risk EG003
Parotid gland enlargement	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Salivary gland pain	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0021 affected219 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0021 affected219 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Exostosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0021 affected219 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0020 affected219 at risk EG003
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0021 affected219 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected219 at risk EG0010 affected218 at risk EG0021 affected219 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Urinary tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment		EG00010 affected219 at risk EG00110 affected218 at risk EG0028 affected219 at risk EG00315 affected220 at risk EG0044 affected107 at risk

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG002 OG003		ANCOVA	ANCOVA: Treatment, geographical region, renal function (screening (eGFR)[MDRD]value)-fixed effects and baseline HbA1c,baseline FPG-linear covariates			Adjusted mean difference	-3.6	Standard Error of the Mean	2.8	95	-9.0	1.8	No	Superiority or Other
OG000 OG001		ANCOVA	ANCOVA: Treatment, geographical region, renal function (screening (eGFR)[MDRD]value)-fixed effects and baseline HbA1c,baseline FPG-linear covariates		The two non-inferiority hypotheses H10 and H20 were tested using the Hochberg procedure in order to control the family-wise type I error at 0.025 (one-sided).	Adjusted mean difference	-5.0	Standard Error of the Mean	2.8	95	-10.4	0.5	No	Superiority or Other
OG000 OG004	Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing FPG after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided)	ANCOVA	ANCOVA:'Treatment','geographical region','renal function'(screening(eGFR)[MDRD]value)-fixed effects and 'baseline HbA1c',baseline FPG-linear covariate	<0.0001		Adjusted mean difference	-27.5	Standard Error of the Mean	3.4	95	-34.2	-20.9	No	Superiority or Other
OG001 OG004	Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing FPG after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided)	ANCOVA	ANCOVA:'Treatment','geographical region','renal function'(screening(eGFR)[MDRD]value)-fixed effects and 'baseline HbA1c',baseline FPG-linear covariate	<0.0001		Adjusted mean difference	-22.5	Standard Error of the Mean	3.4	95	-29.2	-15.9	No	Superiority or Other
OG002 OG004	Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing FPG after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided)	ANCOVA	ANCOVA:'Treatment','geographical region','renal function'(screening(eGFR)[MDRD]value)-fixed effects and 'baseline HbA1c',baseline FPG-linear covariate	<0.0001		Adjusted mean difference	-21.1	Standard Error of the Mean	3.4	95	-27.7	-14.4	No	Superiority or Other
OG003 OG004	Superiority of once daily dose of empagliflozin (10 mg and 25 mg) versus placebo and superiority of twice daily dose of empagliflozin (5 mg and 12.5 mg) versus placebo in reducing FPG after 16 weeks of treatment was tested in an exploratory manner, to demonstrate assay sensitivity against placebo at 0.05 level (two-sided)	ANCOVA	ANCOVA:'Treatment','geographical region','renal function'(screening(eGFR)[MDRD]value)-fixed effects and 'baseline HbA1c',baseline FPG-linear covariate	<0.0001		Adjusted mean difference	-17.5	Standard Error of the Mean	3.4	95	-24.1	-10.8	No	Superiority or Other

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