Study to Evaluate the Efficacy and Safety of Saxagliptin... | NCT02284893

NCT02284893

ID	Type	Description	Link
2014-001102-17	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
A1:Saxagliptin / Placebo + Dapagliflozin / Placebo	Experimental	Saxagliptin 5 mg and matching placebo 0 mg (once daily) plus Dapagliflozin 10 mg and matching placebo 0 mg (once daily)	Drug: Saxagliptin Drug: Dapagliflozin Drug: Placebo matching with Saxagliptin Drug: Placebo matching with Dapagliflozin
A2: Sitagliptin / placebo	Experimental	Sitagliptin 100 mg and matching placebo 0 mg (once daily)	Drug: Sitagliptin Drug: Placebo matching with Sitagliptin

Name	Type	Description	Arm Group Labels	Other Names
Saxagliptin	Drug	administered orally once daily	A1:Saxagliptin / Placebo + Dapagliflozin / Placebo

Measure	Description	Time Frame
Mean Change in HbA1c		Baseline (randomization) to Week 26

Measure	Description	Time Frame
Percent of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%		week 26
Mean Change in Total Body Weight		Baseline (randomization) to Week 26

Eligibility Module

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

Patients with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control, defined as a central laboratory glycosylated hemoglobin (HbA1c) ≥8.0% and ≤ 10.5 % obtained at the screening visit
Subjects should have been taking the same daily dose of metformin ≥ 1500 mg for at least 8 weeks prior to the enrollment visit and with no intake of other antihyperglycemic therapy for more than 14 days (consecutive or not) during 12 weeks prior to screening
BMI > 20.0 kg/m2 at the enrollment visit
Males and Females, age ≥18 years old at time of screening visit
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug
Women must not be breastfeeding

Exclusion Criteria:

Clinically diagnosed with Type I diabetes, known diagnosis of Maturity Onset Diabetes of Young (MODY), secondary diabetes mellitus or diabetes insipidus
History of diabetic ketoacidosis
Any of the following cardiovascular (CV)/Vascular Diseases within 3 months of the enrollment visit
- Myocardial infarction
- Cardiac surgery or revascularization (coronary artery bypass surgery Coronary Artery Bypass Graft [(CABG)]/percutaneous transluminal coronary angioplasty percutaneous transluminal coronary angioplasty [(PTCA)])
- Unstable angina
- Unstable congestive heart failure (CHF)
- Transient ischemic attack (TIA) or significant cerebrovascular disease
- Unstable or previously undiagnosed arrhythmia
- Congestive heart failure, defined as New York Heart Association (NYHA) Class III and IV, unstable or acute congestive heart failure and/or known left ventricular ejection fraction of ≤ 40%
Renal Disease
Hepatic Diseases
Hematological and Oncological Disease/Conditions
Hemoglobin ≤ 11.0 g/dL (110 g/L) for men; hemoglobin ≤ 10.0 g/dL (100 g/L) for women
Abnormal Free T4

Name	Affiliation	Role
Astra Zeneca	AstraZeneca	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Mesa	Arizona	85206	United States
Research Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	SAXA + DAPA + MET	Saxagliptin 5-mg tablet+Dapagliflozin 10-mg tablet+Placebo capsules matching the sitagliptin 100-mg capsules+Metformin background therapy
FG001	SITA + MET

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Mean Change in HbA1c

The Randomized Subjects data set consists of all randomized subjects who received at least

1 dose of double-blind study drug during the double-blind treatment period. Data in this data set were analyzed based on randomized treatment group, even if the treatment they received was different

Posted

Least Squares Mean

Standard Error

percentage (%)

Baseline (randomization) to Week 26

ID	Title	Description
OG000	Saxagliptin + Dapagliflozin + Metformin Group	Saxagliptin 5-mg tablet +Dapagliflozin 10-mg tablet+Metformin background therapy +Placebo capsules matching the sitagliptin 100-mg capsules
OG001	SITA + MET	Placebo tablet matching the saxagliptin 5-mg tablet +Placebo tablet matching the dapagliflozin 10-mg table+Sitagliptin 100-mg capsules +Metformin background therapy

Units	Counts
Participants	OG000224 OG001219

Title

Denominators

Categories

Title	Measurements
	OG000-1.41± 0.0696 OG001-1.07± 0.0719

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		Mixed Models Analysis		0.0008		Mean Difference (Final Values)	-0.34	Standard Error of the Mean	0.1001									Superiority

Secondary

Percent of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%

randomized subjects

Posted

Number

Percentage of subjects

week 26

ID	Title	Description
OG000	Saxagliptin + Dapagliflozin + Metformin Group	Saxagliptin 5-mg tablet +Dapagliflozin 10-mg tablet+Metformin background therapy +Placebo capsules matching the sitagliptin 100-mg capsules
OG001	SITA + MET	Placebo tablet matching the saxagliptin 5-mg tablet +Placebo tablet matching the dapagliflozin 10-mg table+Sitagliptin 100-mg capsules +Metformin background therapy

Units	Counts
Participants	OG000

Secondary

Mean Change in Total Body Weight

randomized subjects

Posted

Mean

Standard Error

Baseline (randomization) to Week 26

ID	Title	Description
OG000	Saxagliptin + Dapagliflozin + Metformin Group	Saxagliptin 5-mg tablet +Dapagliflozin 10-mg tablet+Metformin background therapy +Placebo capsules matching the sitagliptin 100-mg capsules
OG001	SITA + MET	Placebo tablet matching the saxagliptin 5-mg tablet +Placebo tablet matching the dapagliflozin 10-mg table+Sitagliptin 100-mg capsules +Metformin background therapy

Units	Counts
Participants	OG000

Secondary

Mean Change in Fasting Plasma Glucose (FPG)

randomized subjects

Posted

Mean

Standard Error

mg/dl

Baseline (randomization) to Week 26

ID	Title	Description
OG000	Saxagliptin + Dapagliflozin + Metformin Group	Saxagliptin 5-mg tablet +Dapagliflozin 10-mg tablet+Metformin background therapy +Placebo capsules matching the sitagliptin 100-mg capsules
OG001	SITA + MET	Placebo tablet matching the saxagliptin 5-mg tablet +Placebo tablet matching the dapagliflozin 10-mg table+Sitagliptin 100-mg capsules +Metformin background therapy

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
CORONARY ARTERY DISEASE	Cardiac disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
PALPITATIONS	Cardiac disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
CARDIAC FAILURE CHRONIC	Cardiac disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
CARDIAC FAILURE CONGESTIVE	Cardiac disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
CONGESTIVE CARDIOMYOPATHY	Cardiac disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
MITRAL VALVE PROLAPSE	Cardiac disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
TACHYCARDIA	Cardiac disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
GASTROOESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
VOMITING	Gastrointestinal disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
ANAL FISSURE	Gastrointestinal disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
ADENOCARCINOMA OF COLON	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
MENINGIOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
POST LAMINECTOMY SYNDROME	Injury, poisoning and procedural complications	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
LACERATION	Injury, poisoning and procedural complications	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
LOWER LIMB FRACTURE	Injury, poisoning and procedural complications	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
UPPER LIMB FRACTURE	Injury, poisoning and procedural complications	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
DYSFUNCTIONAL UTERINE BLEEDING	Reproductive system and breast disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
ENDOMETRIOSIS	Reproductive system and breast disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0012 affected229 at risk
LUMBAR RADICULOPATHY	Nervous system disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
HEADACHE	Nervous system disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	Vascular disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
DEEP VEIN THROMBOSIS	Vascular disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
MENTAL STATUS CHANGES	Psychiatric disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0010 affected229 at risk
PNEUMONIA	Infections and infestations	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0012 affected229 at risk
SEPSIS	Infections and infestations	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
OSTEOARTHRITIS	Musculoskeletal and connective tissue disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0012 affected229 at risk
ACUTE RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk
DRUG HYPERSENSITIVITY	Immune system disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0011 affected229 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
NASOPHARYNGITIS	Infections and infestations	MEDRA 19.1	Systematic Assessment	EG00018 affected232 at risk EG00112 affected229 at risk
HEADACHE	Nervous system disorders	MEDRA 19.1	Systematic Assessment	EG00013 affected232 at risk EG00110 affected229 at risk
URINARY TRACT INFECTION	Renal and urinary disorders	MEDRA 19.1	Systematic Assessment	EG00010 affected232 at risk EG0017 affected229 at risk
INFLUENZA	Infections and infestations	MEDRA 19.1	Systematic Assessment	EG0008 affected232 at risk EG00111 affected229 at risk
BRONCHITIS	Infections and infestations	MEDRA 19.1	Systematic Assessment	EG0008 affected232 at risk EG0012 affected229 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MEDRA 19.1	Systematic Assessment	EG0007 affected232 at risk EG0018 affected229 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MEDRA 19.1	Systematic Assessment	EG0005 affected232 at risk EG0019 affected229 at risk
DYSLIPIDAEMIA	Congenital, familial and genetic disorders	MEDRA 19.1	Systematic Assessment	EG0005 affected232 at risk EG0013 affected229 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MEDRA 19.1	Systematic Assessment	EG0005 affected232 at risk EG0012 affected229 at risk
SINUSITIS	Infections and infestations	MEDRA 19.1	Systematic Assessment	EG0005 affected232 at risk EG0012 affected229 at risk
VULVOVAGINAL MYCOTIC INFECTION	Infections and infestations	MEDRA 19.1	Systematic Assessment	EG0005 affected232 at risk EG0012 affected229 at risk
GASTROENTERITIS	Infections and infestations	MEDRA 19.1	Systematic Assessment	EG0004 affected232 at risk EG0015 affected229 at risk
GASTROOESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	MEDRA 19.1	Systematic Assessment	EG0005 affected232 at risk EG0011 affected229 at risk
HYPERTENSION	Vascular disorders	MEDRA 19.1	Systematic Assessment	EG0003 affected232 at risk EG0018 affected229 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MEDRA 19.1	Systematic Assessment	EG0003 affected232 at risk EG0017 affected229 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MEDRA 19.1	Systematic Assessment	EG0003 affected232 at risk EG0016 affected229 at risk
DIARRHOEA	Gastrointestinal disorders	MEDRA 19.1	Systematic Assessment	EG0002 affected232 at risk EG0016 affected229 at risk
ANAEMIA	Blood and lymphatic system disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0017 affected229 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0015 affected229 at risk
GASTRITIS	Gastrointestinal disorders	MEDRA 19.1	Systematic Assessment	EG0001 affected232 at risk EG0015 affected229 at risk
HYPERGLYCAEMIA	Endocrine disorders	MEDRA 19.1	Systematic Assessment	EG0000 affected232 at risk EG0015 affected229 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
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines

ID	Title	Description
BG000	SAXA + DAPA + MET	Saxagliptin 5-mg tablet+Dapagliflozin 10-mg tablet+Placebo capsules matching the sitagliptin 100-mg capsules+Metformin background therapy
BG001	SITA + MET	Placebo tablet matching the saxagliptin 5-mg tablet +Placebo tablet matching the dapagliflozin 10-mg table+Sitagliptin 100-mg capsules +Metformin background therapy
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SAXA + DAPA + MET	Saxagliptin 5-mg tablet+Dapagliflozin 10-mg tablet+Placebo capsules matching the sitagliptin 100-mg capsules+Metformin background therapy	0	232	9	232	112	232
EG001	Sita + Met	Placebo tablet matching the saxagliptin 5-mg tablet+Placebo tablet matching the dapagliflozin 10-mg tablet+Sitagliptin 100-mg capsules+Metformin background therapy	0	229	13	229	123	229

ID	Term
C502994	saxagliptin
C529054	dapagliflozin
D000068900	Sitagliptin Phosphate