Efficacy and Safety in Patients With Type 2 Diabetes Mellitus, Cardiovascular Disease and Hypertension - Full Text View

Purpose

This study is carried out to assess whether dapagliflozin lowers blood glucose, body weight and blood pressure, when added to patients existing medications and how it compares with their usual treatment without added dapagliflozin. Safety data will be collected and analysed to confirm that treatment with dapagliflozin is safe and well tolerated in patients who have diabetes, cardiovascular disease and hypertension.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus Cardiovascular Disease Hypertension Inadequate Glycaemic Control	Drug: Dapagliflozin Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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/Day in Pts With T2DM, CV Disease and Hypertension Who Exhibit Inadequate Glycaemic Control on Usual Care

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2 High Blood Pressure

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Adjusted mean change in HbA1c levels [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
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, in the overall population and in the two predefined age subgroups (<65 years, ≥65 years). Primary endpoints are tested at alpha=0.025. Analysis of continuous outcome based on ANCOVA model with treatment group and stratum as effect and baseline value as covariate. Outcome measure type Least Squares Mean represents adjusted mean change from baseline. Difference from placebo: -0.46 (-0.56, -0.37), p<0.0001.
Proportion of responders meeting all criteria of a 3-item endpoint of clinical benefit [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
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 in the overall population and in the two predefined age subgroups. Primary endpoints are tested at alpha=0.025. Analysis based on Cochran-Mantel-Haenszel method with age-by-insulin use-by-time from most recent qualifying CV event as stratum. Outcome measure type Number represents rate of responders. Difference from placebo: 9.9 (7.0, 12.9), p<0.0001.

Secondary Outcome Measures:

Adjusted mean change in seated systolic blood pressure (SBP) [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
To compare the mean change in seated systolic blood pressure from baseline to week 8 between dapagliflozin 10 mg versus placebo, in the overall population and in the two predefined age subgroups (<65 years, ≥65 years). If at least one p-value for primary analysis is significant, key secondary endpoints are tested following a hierarchical closed testing procedure at alpha=0.05/0.025. Analysis of continuous outcome based on ANCOVA model with treatment group and stratum as effect and baseline value as covariate. Outcome measure type Least Squares Mean represents adjusted mean change from baseline. Difference from placebo: -1.97 (-3.52, -0.42), p=0.0126.
Adjusted mean percent change in body weight [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
To compare the mean percent change in body weight from baseline to week 24 between dapagliflozin 10 mg versus placebo, in the overall population and in the two predefined age subgroups (<65 years, ≥65 years). If at least one p-value for primary analysis is significant, key secondary endpoints are tested following a hierarchical closed testing procedure at alpha=0.05/0.025. Analysis of continuous outcome based on ANCOVA model with treatment group and stratum as effect and baseline value as covariate. Outcome measure type Least Squares Mean represents adjusted mean change from baseline. Difference from placebo: -2.27 (-2.64, -1.89), p<0.0001.
Adjusted mean change in seated systolic blood pressure (SBP) at Week 24 (LOCF) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
To compare the mean change in seated systolic blood pressure from baseline to week 24 between dapagliflozin 10 mg versus placebo, in the overall population and in the two predefined age subgroups (<65 years, ≥65 years). If at least one p-value for primary analysis is significant, key secondary endpoints are tested following a hierarchical closed testing procedure at alpha=0.05/0.025. Analysis of continuous outcome based on ANCOVA model with treatment group and stratum as effect and baseline value as covariate. Outcome measure type Least Squares Mean represents adjusted mean change from baseline. Difference from placebo: -1.95 (-3.56, -0.34), p=0.0174.
Proportion of participants with a reduction from baseline of 5% or more in body weight in participants with baseline BMI ≥27 kg/m² [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
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, in the overall population and in the two predefined age subgroups (<65 years, ≥65 years).

If at least one p-value for primary analysis is significant, key secondary endpoints are tested following a hierarchical closed testing procedure at alpha=0.05/0.025. Logistic regression analysis of responses based on methodology of Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu, with adjustment for baseline weight and stratum. Outcome measure type Least Squares Mean represents adjusted percent. Difference from placebo: 12.5 (8.3, 16.6), p<0.0001.

Enrollment:	922
Study Start Date:	February 2010
Study Completion Date:	December 2012
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Dapagliflozin 10 mg tablet	Drug: Dapagliflozin 10 mg tablet, oral, once daily, 24- week treatment and 80-week extension period
Placebo Comparator: 2 Matching placebo tablet	Drug: Placebo Matching placebo tablet, oral, once daily, 24- week treatment and 80-week extension period

Eligibility

Ages Eligible for Study:	45 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Type 2 diabetes mellitus.
Cardiovascular disease
Hypertension

Exclusion Criteria:

Patients with type 1 diabetes or diabetes insipidus
Patients with 3 or more oral anti-hyperglycaemic drugs with or without insulin and/or poorly controlled diabetes
Any clinically significant illness, which would compromise the patient's safety and their participation in the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01031680

Show 137 Study Locations

Sponsors and Collaborators

AstraZeneca

Bristol-Myers Squibb

Investigators

Principal Investigator:

Dr. William Cefalu

Pennington Biomedical Research Center

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01031680 History of Changes
Other Study ID Numbers:	D1690C00018
Study First Received:	December 10, 2009
Last Updated:	December 27, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

dapagliflozin
diabetes
cardiovascular disease
hypertension

Additional relevant MeSH terms:

Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension

Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on June 17, 2013