Evaluation of Dapagliflozin Taken Twice-daily | NCT01217892

Name	Class
Bristol-Myers Squibb	INDUSTRY

Evaluation of Dapagliflozin Taken Twice-daily | NCT01217892 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1	Experimental	Dapagliflozin 2.5 mg twice-daily plus open-label metformin	Drug: dapagliflozin Drug: metformin
2	Experimental	Dapagliflozin 5.0 mg twice-daily plus open-label metformin	Drug: dapagliflozin Drug: metformin
3	Experimental	Dapagliflozin 10 mg once-daily plus open-label metformin	Drug: dapagliflozin Drug: metformin
4	Placebo Comparator	Placebo plus open-label metformin	Drug: metformin Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
dapagliflozin	Drug	2.5 mg tablet, taken orally, twice daily	1
dapagliflozin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Adjusted Mean Change in HbA1c Levels	To compare the change from baseline in HbA1c achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment.	Baseline to Week 16

Secondary Outcomes

Measure	Description	Time Frame
Adjusted Percent Change in Body Weight	To compare the percent change from baseline in body weight achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID, and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment.	Baseline to Week 16

Contacts/Locations Module

Name	Affiliation	Role
Shamik Parikh	AstraZeneca	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Aßlar			Germany
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25200570	Background	Schumm-Draeger PM, Burgess L, Koranyi L, Hruba V, Hamer-Maansson JE, de Bruin TW. Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: a 16-week randomized, placebo-controlled clinical trial. Diabetes Obes Metab. 2015 Jan;17(1):42-51. doi: 10.1111/dom.12387. Epub 2014 Oct 16.

Label	URL
CSR-D1691C00003.pdf	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Dapagliflozin 2.5mg BID Plus Metformin	Dapagliflozin 2.5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
FG001	Dapagliflozin 5mg BID Plus Metformin

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Adverse Event		FG0001 subjects FG0011 subjects FG0021 subjects FG0030 subjects
Withdrawal by Subject		FG0000 subjects FG0012 subjects FG0021 subjects FG0030 subjects
Lab value		FG0001 subjects FG0010 subjects FG0021 subjects FG0030 subjects
Subject no longer meets study criteria		FG0005 subjects FG0012 subjects FG0024 subjects FG0038 subjects
Incorrect enrollment		FG0000 subjects FG0011 subjects FG0021 subjects FG0030 subjects
Poor/Non-Compliance		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects

Arm/Group Information

ID	Title	Description
BG000	Dapagliflozin 2.5mg BID Plus Metformin	Dapagliflozin 2.5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
BG001	Dapagliflozin 5mg BID Plus Metformin	Dapagliflozin 5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
BG002	Dapagliflozin 10mg OD Plus Metformin	Dapagliflozin 10mg, oral, once daily plus Metformin, oral, twice daily, >=1500mg total daily dose
BG003	Placebo Plus Metformin	Placebo plus Metformin, oral, twice daily, >=1500mg total daily dose
BG004	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
	BG00058.3± 9.01 BG00155.3± 9.34 BG00258.5± 9.78 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00063 BG00153 BG002

HbA1c

Mean

Standard Deviation

Percent [%]

Title

Denominators

Categories

Title	Measurements
	BG0007.77± 0.747 BG0017.78± 0.762 BG002

Fasting Plasma Glucose (FPG)

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000153.3± 33.27 BG001155.3± 31.92 BG002

Body weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00092.49± 18.632 BG00193.62± 16.641 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Adjusted Mean Change in HbA1c Levels

To compare the change from baseline in HbA1c achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment.

Full Analysis Set, participants with non-missing baseline and Week 16 (LOCF) values

Posted

Least Squares Mean

Standard Error

Percent

Baseline to Week 16

ID	Title	Description
OG000	Dapagliflozin 2.5mg BID Plus Metformin	Dapagliflozin 2.5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG001	Dapagliflozin 5mg BID Plus Metformin	Dapagliflozin 5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG002	Dapagliflozin 10mg OD Plus Metformin	Dapagliflozin 10mg, oral, once daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG003	Placebo Plus Metformin	Placebo plus Metformin, oral, twice daily, >=1500mg total daily dose

Units	Counts
Participants	OG00099 OG00197 OG00298 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.52± 0.0594(-0.63 to -0.40) OG001-0.65± 0.0600(-0.77 to -0.53) OG002-0.59± 0.0598(-0.70 to -0.47)

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 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.05 using Hochberg's method to control the overall Type I error across hypotheses in the two Dapagliflozin BID groups, two-sided)	ANCOVA	with treatment group as effect (all treatment groups included) and baseline value as covariate.	0.0106	significant at alpha=0.05 (2-sided) applying Hochberg's method across the two Dapagliflozin BID groups.	Mean Difference (Final Values)	-0.22	Standard Error of the Mean	0.0840	2-Sided	95	-0.38	-0.05				No

Secondary

Adjusted Percent Change in Body Weight

To compare the percent change from baseline in body weight achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID, and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment.

Full Analysis Set, participants with non-missing baseline and Week 16 (LOCF) values

Posted

Least Squares Mean

Standard Error

Percent

Baseline to Week 16

ID	Title	Description
OG000	Dapagliflozin 2.5mg BID Plus Metformin	Dapagliflozin 2.5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG001	Dapagliflozin 5mg BID Plus Metformin	Dapagliflozin 5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG002	Dapagliflozin 10mg OD Plus Metformin	Dapagliflozin 10mg, oral, once daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG003	Placebo Plus Metformin

Secondary

Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 1

To compare the change from baseline in fasting plasma glucose (FPG) achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 1 week of double-blind treatment.

Full Analysis Set, participants with non-missing baseline and Week 1 values

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline to Week 1

ID	Title	Description
OG000	Dapagliflozin 2.5mg BID Plus Metformin	Dapagliflozin 2.5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG001	Dapagliflozin 5mg BID Plus Metformin	Dapagliflozin 5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG002	Dapagliflozin 10mg OD Plus Metformin	Dapagliflozin 10mg, oral, once daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG003	Placebo Plus Metformin

Secondary

Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 16

Full Analysis Set, participants with non-missing baseline and Week 16 (LOCF) values

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline to Week 16

ID	Title	Description
OG000	Dapagliflozin 2.5mg BID Plus Metformin	Dapagliflozin 2.5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG001	Dapagliflozin 5mg BID Plus Metformin	Dapagliflozin 5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG002	Dapagliflozin 10mg OD Plus Metformin	Dapagliflozin 10mg, oral, once daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG003	Placebo Plus Metformin

Secondary

Proportion of Participants With HbA1c<7.0% at Week 16, in Participants Who Had HbA1c ≥7.0% at Baseline.

To compare the adjusted proportions controlling for baseline HbA1c [acc. to Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu] of participants with HbA1c <7.0% achieved with each of the 2 BID doses of dapagliflozin (2.5 mg BID and 5 mg BID) co-administered with metformin versus placebo co-administered with metformin after 16 weeks of double-blind treatment, in patients who had HbA1c ≥7.0% at baseline.

Full Analysis Set, participants with non-missing baseline and Week 16 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

Percentage of participants

Baseline to Week 16

ID	Title	Description
OG000	Dapagliflozin 2.5mg BID Plus Metformin	Dapagliflozin 2.5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG001	Dapagliflozin 5mg BID Plus Metformin	Dapagliflozin 5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose
OG002	Dapagliflozin 10mg OD Plus Metformin	Dapagliflozin 10mg, oral, once daily plus Metformin, oral, twice daily, >=1500mg total daily dose

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dapagliflozin 2.5mg BID Plus Metformin	Dapagliflozin 2.5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose	4	100	8	100
EG001	Dapagliflozin 5mg BID Plus Metformin	Dapagliflozin 5mg, oral, twice daily plus Metformin, oral, twice daily, >=1500mg total daily dose	1	100	0	100
EG002	Dapagliflozin 10mg OD Plus Metformin	Dapagliflozin 10mg, oral, once daily plus Metformin, oral, twice daily, >=1500mg total daily dose	2	99	6	99
EG003	Placebo Plus Metformin	Placebo plus Metformin, oral, twice daily, >=1500mg total daily dose	0	101	9	101

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
SICK SINUS SYNDROME	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected100 at risk EG0010 affected100 at risk EG0021 affected99 at risk EG0030 affected101 at risk
CARDIAC FAILURE	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected100 at risk EG0011 affected100 at risk EG0020 affected99 at risk EG003
HYPERTENSIVE CRISIS	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected100 at risk EG0010 affected100 at risk EG0021 affected99 at risk EG003
FEMORAL ARTERY OCCLUSION	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected100 at risk EG0010 affected100 at risk EG0020 affected99 at risk EG003
ENDOMETRITIS	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected100 at risk EG0010 affected100 at risk EG0020 affected99 at risk EG003
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected100 at risk EG0010 affected100 at risk EG0020 affected99 at risk EG003
HAEMOPTYSIS	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected100 at risk EG0010 affected100 at risk EG0020 affected99 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
INFLUENZA	Infections and infestations	MedDRA 14.0	Systematic Assessment		EG0005 affected100 at risk EG0010 affected100 at risk EG0022 affected99 at risk EG0033 affected101 at risk
HYPERTENSION	Vascular disorders	MedDRA 14.0	Systematic Assessment		EG0003 affected100 at risk EG0010 affected100 at risk EG0024 affected99 at risk EG003

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 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.05, two-sided)	ANCOVA	with treatment group (all treatment groups included) and stratum (HbA1c <7.0% vs >=7.0% at randomization) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group for treatment groups tested significantly different from placebo for the primary endpoint.	Mean Difference (Final Values)	-1.82	Standard Error of the Mean	0.3630	2-Sided	95	-2.53	-1.10				No	Superiority or Other
OG001 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.05, two-sided)	ANCOVA	with treatment group (all treatment groups included) and stratum (HbA1c <7.0% vs >=7.0% at randomization) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group for treatment groups tested significantly different from placebo for the primary endpoint.	Mean Difference (Final Values)	-2.18	Standard Error of the Mean	0.3636	2-Sided	95	-2.89	-1.46				No	Superiority or Other

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 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.05, two-sided)	ANCOVA	with treatment group (all treatment groups included) and stratum (HbA1c <7.0% vs >=7.0% at randomization) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group for treatment groups tested significantly different from placebo for the primary endpoint.	Mean Difference (Final Values)	-15.7	Standard Error of the Mean	3.040	2-Sided	95	-21.7	-9.7				No	Superiority or Other
OG001 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.05, two-sided)	ANCOVA	with treatment group (all treatment groups included) and stratum (HbA1c <7.0% vs >=7.0% at randomization) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group for treatment groups tested significantly different from placebo for the primary endpoint.	Mean Difference (Final Values)	-16.7	Standard Error of the Mean	3.039	2-Sided	95	-22.7	-10.7				No	Superiority or Other

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 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.05, two-sided)	ANCOVA	with treatment group (all treatment groups included) and stratum (HbA1c <7.0% vs >=7.0% at randomization) as effect and baseline value as covariate.	0.0010	significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group for treatment groups tested significantly different from placebo for the primary endpoint.	Mean Difference (Final Values)	-10.4	Standard Error of the Mean	3.132	2-Sided	95	-16.5	-4.2				No	Superiority or Other
OG001 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.05, two-sided)	ANCOVA	with treatment group (all treatment groups included) and stratum (HbA1c <7.0% vs >=7.0% at randomization) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group for treatment groups tested significantly different from placebo for the primary endpoint.	Mean Difference (Final Values)	-15.3	Standard Error of the Mean	3.139	2-Sided	95	-21.4	-9.1				No	Superiority or Other

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 OG003	H0: proportion(treat) minus proportion(placebo) = 0 versus the alternative HA: proportion(treat) minus proportion(placebo) =/= 0	Regression, Logistic	Methodology of Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu, with adjustment for baseline value.	0.0455	significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group for treatment groups tested significantly different from placebo for the primary endpoint.	Risk Difference (RD)	12.2	Standard Error of the Mean	6.097	2-Sided	95	0.2	24.1				No	Superiority or Other
OG001 OG003	H0: proportion(treat) minus proportion(placebo) = 0 versus the alternative HA: proportion(treat) minus proportion(placebo) =/= 0	Regression, Logistic	Methodology of Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu, with adjustment for baseline value.	0.0062	significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group for treatment groups tested significantly different from placebo for the primary endpoint.	Risk Difference (RD)	16.8	Standard Error of the Mean	6.153	2-Sided	95	4.8	28.9				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

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals