Safety and Efficacy of Combination Saxagliptin & Dapaglif... | NCT01606007

NCT01606007

ID	Type	Description	Link
2012-000679-18	EudraCT Number

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Arm 1: Saxagliptin+Metformin XR+Placebo	Active Comparator	Drug: Saxagliptin Drug: Metformin XR Drug: Placebo matching with Dapagliflozin
Arm 2: Dapagliflozin+Metformin XR+Placebo	Active Comparator	Drug: Metformin XR Drug: Dapagliflozin Drug: Placebo matching with Saxagliptin
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR	Experimental	Drug: Saxagliptin Drug: Metformin XR Drug: Dapagliflozin

Name	Type	Description	Arm Group Labels	Other Names
Saxagliptin	Drug	Tablets, Oral, 5mg , Once daily, 24 weeks	Arm 1: Saxagliptin+Metformin XR+Placebo Arm 3: Saxagliptin+Dapagliflozin+Metformin XR

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24	HbA1c was measured as percent of hemoglobin by a central laboratory. Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained at Week 24 in the double-blind period, including observations prior to rescue.	Baseline (Week 0) and at Week 24

Secondary Outcomes

Measure	Description	Time Frame
Adjusted Mean Change From Baseline in 2-hour Post Prandial Glucose (PPG) From a Liquid Meal Tolerance Test (MTT) at Week 24 (Last Observation Carried Forward [LOCF])	Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PPG measurements were obtained at week 24 in the doubleblind period, including observations prior to rescue.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Central Alabama Research		Birmingham	Alabama	35209	United States
Central Alabama Research

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25352655	Result	Rosenstock J, Hansen L, Zee P, Li Y, Cook W, Hirshberg B, Iqbal N. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care. 2015 Mar;38(3):376-83. doi: 10.2337/dc14-1142. Epub 2014 Oct 28.
31364269

Label	URL
CV\_181169\_Protocol\_Redacted	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm 1: Saxagliptin+Metformin XR+Placebo	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Arm/Group Information

ID	Title	Description
BG000	Arm 1: Saxagliptin+Metformin XR+Placebo	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
BG001	Arm 2: Dapagliflozin+Metformin XR+Placebo	Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
BG002	Arm 3: Saxagliptin+Dapagliflozin+Metformin XR	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
BG003	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
	BG00054.6± 9.6 BG00153.5± 9.7 BG00253.4± 9.8 BG003

Age, Customized

Number

participants

Title

Denominators

Categories

<65 years

Title	Measurements
	BG000148 BG001158 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00082 BG00190 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

White

Title	Measurements
	BG000121 BG001131 BG002

Body Mass Index (BMI)

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00031.8± 5.142 BG00131.46± 5.321 BG002

T2DM duration

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0008.2± 5.52 BG0017.4± 5.40 BG002

HbA1c

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG0009.03± 1.05 BG0018.87± 1.16 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 From Baseline in Hemoglobin A1C (HbA1c) at Week 24

HbA1c was measured as percent of hemoglobin by a central laboratory. Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained at Week 24 in the double-blind period, including observations prior to rescue.

All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 24

Posted

Mean

95% Confidence Interval

% HbA1c

Baseline (Week 0) and at Week 24

ID	Title	Description
OG000	Arm 1: Saxagliptin+Metformin XR+Placebo	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
OG001	Arm 2: Dapagliflozin+Metformin XR+Placebo	Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
OG002	Arm 3: Saxagliptin+Dapagliflozin+Metformin XR	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148

Units	Counts
Participants	OG000143 OG001151 OG002158

Title

Denominators

Categories

Title	Measurements
	OG000-0.88(-1.03 to -0.72) OG001-1.20(-1.35 to -1.04) OG002-1.47(-1.62 to -1.31)

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 OG002		Mixed Models Analysis		<0.0001	Primary endpoint was tested at alpha=0.05; significance was claimed only if Saxagliptin+Dapagliflozin+Metformin was superior to both Saxagliptin+Metformin and Dapagliflozin+Metformin.	Mean Difference (Final Values)	-0.59	Standard Error of the Mean	0.1112	2-Sided	95	-0.81	-0.37					Superiority or Other

Secondary

Adjusted Mean Change From Baseline in 2-hour Post Prandial Glucose (PPG) From a Liquid Meal Tolerance Test (MTT) at Week 24 (Last Observation Carried Forward [LOCF])

Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PPG measurements were obtained at week 24 in the doubleblind period, including observations prior to rescue.

All randomized participants who received study medication and had nonmissing PPG values at baseline and Week 24 (LOCF)

Posted

Mean

95% Confidence Interval

MG/DL PPG

Baseline (Week 0) and at Week 24

ID	Title	Description
OG000	Arm 1: Saxagliptin+Metformin XR+Placebo	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
OG001	Arm 2: Dapagliflozin+Metformin XR+Placebo	Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
OG002	Arm 3: Saxagliptin+Dapagliflozin+Metformin XR

Secondary

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

Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained at Week 24 in the doubleblind period, including observations prior to rescue.

All randomized participants who received study medication and had nonmissing PPG values at baseline and Week 24

Posted

Mean

95% Confidence Interval

mg/dL

Baseline (Week 0) and at Week 24

ID	Title	Description
OG000	Arm 1: Saxagliptin+Metformin XR+Placebo	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
OG001	Arm 2: Dapagliflozin+Metformin XR+Placebo	Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
OG002	Arm 3: Saxagliptin+Dapagliflozin+Metformin XR

Secondary

Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])

Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.

All randomized participants who received study medication and were not missing baseline and Week 24 (LOCF) values

Posted

Number

95% Confidence Interval

% of Participants

At Week 24

ID	Title	Description
OG000	Arm 1: Saxagliptin+Metformin XR+Placebo	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
OG001	Arm 2: Dapagliflozin+Metformin XR+Placebo	Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
OG002	Arm 3: Saxagliptin+Dapagliflozin+Metformin XR

Secondary

Adjusted Mean Change From Baseline in Body Weight at Week 24

Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained at Week 24 in the doubleblind period, including observations prior to rescue.

All randomized participants who received study medication and had nonmissing body weight values at baseline and Week 24

Posted

Mean

95% Confidence Interval

Body weight Kg

Baseline (Week 0) and at Week 24

ID	Title	Description
OG000	Arm 1: Saxagliptin+Metformin XR+Placebo	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
OG001	Arm 2: Dapagliflozin+Metformin XR+Placebo	Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
OG002	Arm 3: Saxagliptin+Dapagliflozin+Metformin XR

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (At Risk)
EG000	SAXA + MET	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks	6	176	176
EG001	DAPA + MET	Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks	2	179	179
EG002	SAXA + DAPA + MET	Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148	2	179	179

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ACUTE MYOCARDIAL INFARCTION	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0010 events0 affected179 at risk EG0021 events1 affected179 at risk
PANCREATITIS CHRONIC	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0010 events0 affected179 at risk EG0021 events1 affected179 at risk
UMBILICAL HERNIA	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected179 at risk EG0020 events0 affected179 at risk
CHEST PAIN	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected179 at risk EG0020 events0 affected179 at risk
TOOTH INFECTION	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected179 at risk EG0020 events0 affected179 at risk
PATELLA FRACTURE	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected179 at risk EG0020 events0 affected179 at risk
HYPERKALAEMIA	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected179 at risk EG0020 events0 affected179 at risk
ARTHRITIS	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected179 at risk EG0020 events0 affected179 at risk
GASTRIC NEOPLASM	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0010 events0 affected179 at risk EG0021 events1 affected179 at risk
TRANSIENT ISCHAEMIC ATTACK	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected179 at risk EG0020 events0 affected179 at risk
BENIGN PROSTATIC HYPERPLASIA	Reproductive system and breast disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected179 at risk EG0020 events0 affected179 at risk
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected179 at risk EG0020 events0 affected179 at risk
DEEP VEIN THROMBOSIS	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected179 at risk EG0020 events0 affected179 at risk

Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148

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