Efficacy and Safety in Patients With Type 2 Diabetes Mell... | NCT01031680

Official Title

A 24-week, Multicentre, Randomised, Double-blind, Age-stratified, Placebo Controlled, Phase III Study With a 80-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin 10 mg Once Daily in Pts With T2DM, CV Disease and Hypertension Who Exhibit Inadequate Glycaemic Control on Usual Care

Status Module

Name	Class
Bristol-Myers Squibb	INDUSTRY

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
1	Experimental	Dapagliflozin 10 mg tablet	Drug: Dapagliflozin
2	Placebo Comparator	Matching placebo tablet	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Dapagliflozin	Drug	10 mg tablet, oral, once daily, 24- week treatment and 80-week extension period	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Adjusted Mean Change in HbA1c Levels	To compare the glycemic efficacy of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease and hypertension, measured as the mean change in HbA1c from baseline to week 24.	Baseline to Week 24
Proportion of Responders Meeting All Criteria of a 3-item Endpoint of Clinical Benefit	To compare the clinical benefit of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease and hypertension at week 24, measured as the proportion of responders for a 3-item endpoint of clinical benefit, defined as an absolute drop of 0.5% or more from baseline HbA1c, and a relative drop of 3% or more from baseline for total body weight, and an absolute drop of 3 mmHg or more from baseline in seated systolic blood pressure.	Baseline to week 24

Secondary Outcomes

Measure	Description	Time Frame
Adjusted Mean Change in Seated Systolic Blood Pressure (SBP)	To compare the mean change in seated systolic blood pressure from baseline to week 8 between dapagliflozin 10 mg versus placebo.	Baseline to Week 8
Adjusted Mean Percent Change in Body Weight

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Dr. William Cefalu	Pennington Biomedical Research Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Gulf Shores	Alabama		United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38770818	Derived	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.
25852208

Results Section

Participant Flow Module

ID	Title	Description
FG000	Experimental	Dapagliflozin, 10 mg tablet, oral, once daily
FG001	Placebo Comparator	Placebo, Matching placebo tablet, oral, once daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Full Analysis Set defined as all randomized participants (as randomized) who received at least one dose of double-blind study medication, who have a non-missing baseline value and at least one post-baseline efficacy value for at least one efficacy variable during double-blind treatment period.

Arm/Group Information

ID	Title	Description
BG000	Experimental	Dapagliflozin, 10 mg tablet, oral, once daily
BG001	Placebo Comparator	Placebo, Matching placebo tablet, oral, once daily
BG002	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
	BG00062.8± 6.97 BG00163.0± 7.66 BG00262.9± 7.32

Age, Customized

Number

Participants

Title

Denominators

Categories

<55

Title	Measurements
	BG00058 BG00174 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000146 BG001144 BG002

Haemoglobin A1c (HbA1c)

Mean

Standard Deviation

Percent

Title

Denominators

Categories

Title	Measurements
	BG0008.18± 0.841 BG0018.08± 0.802 BG002

Seated Systolic Blood Pressure

Mean

Standard Deviation

mm Hg

Title

Denominators

Categories

Title	Measurements
	BG000133.5± 13.48 BG001133.0± 13.81 BG002

Total Body Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00092.63± 20.504 BG00193.59± 19.467 BG002

Body Mass Index (BMI)

Number

Participants

Title

Denominators

Categories

< 25 kg/m²

Title	Measurements
	BG00029 BG00130 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 glycemic efficacy of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease and hypertension, measured as the mean change in HbA1c from baseline to week 24.

Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

Percent

Baseline to Week 24

ID	Title	Description
OG000	Experimental	Dapagliflozin, 10 mg tablet, oral, once daily
OG001	Placebo Comparator	Placebo, Matching placebo tablet, oral, once daily

Units	Counts
Participants	OG000448 OG001451

Title

Denominators

Categories

Title	Measurements
	OG000-0.38(-0.46 to -0.30) OG0010.08(0.01 to 0.16)

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 OG001	H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA	with treatment group and stratum as effects and baseline value as covariate for each endpoint	<0.0001	Significant at alpha=0.025 (2-sided). A hierarchical closed testing procedure was used to control Type I error across the primary & key secondary objectives	Mean Difference (Final Values)	-0.46	Standard Error of the Mean	0.0473	2-Sided	95	-0.56	-0.37			with stratum = age-by-insulin use-by-time from most recent qualifying CV event	No

Primary

Proportion of Responders Meeting All Criteria of a 3-item Endpoint of Clinical Benefit

To compare the clinical benefit of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease and hypertension at week 24, measured as the proportion of responders for a 3-item endpoint of clinical benefit, defined as an absolute drop of 0.5% or more from baseline HbA1c, and a relative drop of 3% or more from baseline for total body weight, and an absolute drop of 3 mmHg or more from baseline in seated systolic blood pressure.

Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline to week 24

ID	Title	Description
OG000	Experimental	Dapagliflozin, 10 mg tablet, oral, once daily
OG001	Placebo Comparator	Placebo, Matching placebo tablet, oral, once daily

Units	Counts
Participants

Secondary

Adjusted Mean Change in Seated Systolic Blood Pressure (SBP)

To compare the mean change in seated systolic blood pressure from baseline to week 8 between dapagliflozin 10 mg versus placebo.

Full Analysis Set, participants with non-missing baseline and Week 8 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

mmHg

Baseline to Week 8

ID	Title	Description
OG000	Experimental	Dapagliflozin, 10 mg tablet, oral, once daily
OG001	Placebo Comparator	Placebo, Matching placebo tablet, oral, once daily

Units	Counts
Participants	OG000

Secondary

Adjusted Mean Percent Change in Body Weight

To compare the mean percent change in body weight from baseline to week 24 between dapagliflozin 10 mg versus placebo.

Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

Percentage of Body Weight

Baseline to Week 24

ID	Title	Description
OG000	Experimental	Dapagliflozin, 10 mg tablet, oral, once daily
OG001	Placebo Comparator	Placebo, Matching placebo tablet, oral, once daily

Units	Counts
Participants	OG000

Secondary

Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 24 (LOCF)

To compare the mean change in seated systolic blood pressure from baseline to week 24 between dapagliflozin 10 mg versus placebo.

Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

mmHg

Baseline to Week 24

ID	Title	Description
OG000	Experimental	Dapagliflozin, 10 mg tablet, oral, once daily
OG001	Placebo Comparator	Placebo, Matching placebo tablet, oral, once daily

Units	Counts
Participants	OG000

Secondary

Proportion of Participants With a Reduction From Baseline of 5% or More in Body Weight in Participants With Baseline BMI ≥27 kg/m²

To compare the proportion of participants with BMI baseline ≥27 kg/m2 with a reduction from baseline of 5% or more in body weight with dapagliflozin 10 mg versus placebo from baseline to week 24. Least Squares Mean represents the percent of participants adjusted for baseline body weight and age stratum.

Full analysis set; participants with baseline BMI ≥27 kg/m² and Week 24 (LOCF) body weight value

Posted

Least Squares Mean

95% Confidence Interval

Percentage of participants

Baseline to Week 24

ID	Title	Description
OG000	Experimental	Dapagliflozin, 10 mg tablet, oral, once daily
OG001	Placebo Comparator	Placebo, Matching placebo tablet, oral, once daily

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Experimental	Dapagliflozin, 10 mg tablet, oral, once daily			27	460	89	460
EG001	Placebo Comparator	Placebo, Matching placebo tablet, oral, once daily			26	462	84	462

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Gastroenteritis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected460 at risk EG0011 affected462 at risk
Anal Abscess	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Diarrhoea Infectious	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Diverticulitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Gangrene	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0011 affected462 at risk
Localised Infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Nasopharyngitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Otitis Media	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0011 affected462 at risk
Septic Shock	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Abscess Limb	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Lung Infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Acute Coronary Syndrome	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0011 affected462 at risk
Angina Pectoris	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Angina Unstable	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0013 affected462 at risk
Cardiogenic Shock	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Coronary Artery Disease	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0011 affected462 at risk
Atrial Flutter	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Gastric Ulcer	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Peptic Ulcer	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Peritonitis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Gastritis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Diabetic Foot	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Bladder Transitional Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0002 affected460 at risk EG0010 affected462 at risk
Basal Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0011 affected462 at risk
Chest Pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0012 affected462 at risk
Sudden Death	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0011 affected462 at risk
Ischaemic Stroke	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0011 affected462 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Epicondylitis	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Alcohol Poisoning	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Ankle Fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Patella Fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Osteitis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Depression	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Renal Failure Acute	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Hypertensive Crisis	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected460 at risk EG0010 affected462 at risk
Arteriosclerosis Obliterans	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Hypertension	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Vascular Occlusion	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk
Unassigned	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected460 at risk EG0011 affected462 at risk

Certain Agreements

ID	Term
D003924	Diabetes Mellitus, Type 2
D002318	Cardiovascular Diseases
D006973	Hypertension
D003920	Diabetes Mellitus

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D014652	Vascular Diseases