This study is being carried out to evaluate the effect of a drug called dapagliflozin when added to current treatment for type 2 diabetes on cardiovascular events.

• Register: EUCTR
• Last refreshed on: 12 November 2018
• Main ID: EUCTR2013-000239-28-PL
• Date of registration: 27/08/2013
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: This study is being carried out to evaluate the effect of a drug called dapagliflozin when added to current treatment for type 2 diabetes on cardiovascular events.
• Scientific title: DECLARE Dapagliflozin Effect on CardiovascuLAR Events A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effect of Dapagliflozin 10 mg Once Daily on the Incidence of Cardiovascular Death, Myocardial Infarction or Ischemic Stroke in Patients with Type 2 Diabetes - DECLARE
• Date of first enrolment: 15/10/2013
• Target sample size: 17150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000239-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, European Union, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Philippines, Poland, Russian Federation, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Information Center
• Affiliation: AstraZeneca

• Name: Information Center
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion criteria:
For inclusion in the study patients should fulfill the following criteria:
1. Provision of informed consent prior to any study specific procedures (including run-in)
2. Female or male aged = 40 years
3. Diagnosed with T2DM (See Appendix E for details)
4. High Risk for CV event defined as having either established CV disease and/or multiple risk factors:
- Established CV Disease (See Appendix E for details)
OR
No known cardiovascular disease AND at least two cardiovascular risk factors in addition to T2DM, defined as:
- Age = 55 years in men and = 60 in women
AND presence of at least 1 of the following additional risk factors (see Appendix E for details)
- Dyslipidemia
- Hypertension
- Current Tobacco use
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8575

Exclusion criteria:
1. Use of the following excluded medications:
- Current or recent (within 24 months) treatment with pioglitazone
and/or use of pioglitazone for a total of 2 years or more during lifetime
- Current or recent (within 12 months) treatment with rosiglitazone
- Previous treatment with any SGLT2 inhibitor
- Any patient currently receiving chronic (>30 consecutive days)
treatment with an oral steroid at a dose equivalent to oral prednisolone
=10 mg (e.g., betamethasone =1.2 mg, dexamethasone =1.5 mg,
hydrocortisone =40 mg) per day
2. Acute cardiovascular event[e.g., acute coronary syndrome (ACS),
transient ischemic attack (TIA), stroke, any revascularization,
decompensated HF, sustained ventricular tachycardia <8 weeks prior to
randomization. Patients with acute cardiovascular events can be enrolled
in the run-in period as long as randomization does not occur within 8
weeks of the event.
3. Systolic BP> 180 or diastolic BP > 100 mmHg at randomization.
Patient should be excluded if either the systolic BP is elevated (> 180
mmHg) or the diastolic BP is elevated (> 100 mmHg) on both
measurements
4. Diagnosis of Type 1 diabetes mellitus, MODY, or secondary diabetes
mellitus
5. History of bladder cancer or history of radiation therapy to the lower
abdomen or pelvis at any time
6. History of any other malignancy within 5 years (with the exception of
successfully treated non-melanoma skin cancers)
7. Chronic cystitis and/or recurrent urinary tract infections (3 or more in
the last year)
8. Any conditions that, in the opinion of the Investigator, may render the
patient unable to complete the study including but not limited to
cardiovascular (NYHA class IV CHF, recurrent ventricular arrhythmias)
or non-cardiovascular disease (e.g., active malignancy with the
exception of basal cell carcinoma, cirrhosis, chronic lung disease, severe
autoimmune disease) and/or a likely fatal outcome within 5 years
9. Pregnant or breast-feeding patients
Patients will be excluded during run-in and should not be randomized if
the following are observed from laboratory or observation during
enrollment and run-in assessments:
10. HbA1c =12% or HbA1c<6.5% from the central laboratory (nb, the
proportion of subjects with an HbA1c between 6.5 % and < 7.0 % will be
capped at approximately 5 % of the study)
11. AST or ALT >3x ULN or Total bilirubin >2.5 x ULN
12. CrCl < 60 ml/min (based on the Cockroft-Gault equation)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 Diabetes mellitus
MedDRA version: 20.0 Level: SOC Classification code 10027433 Term: Metabolism and nutrition disorders System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 20.0 Level: LLT Classification code 10012613 Term: Diabetes mellitus non-insulin-dependent System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Forxiga
Product Name: Dapagliflozin
Product Code: BMS-512148
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: dapagliflozin
CAS Number: 960404-48-2
Current Sponsor code: BMS-512148-05
Other descriptive name: DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: This will be evaluated at the pre-specified interim analysis and when the
study has been completed.

Main Objective: The primary objective is to determine the effect of dapagliflozin relative
to placebo on cardiovascular outcome when added to current
background therapy in patients with type 2 diabetes mellitus (T2DM)
with either established cardiovascular disease or at least two
cardiovascular risk factors.

Secondary Objective: The secondary objective is to determine whether treatment with
dapagliflozin relative to placebo when added to current background
therapy in patients with type 2 diabetes mellitus (T2DM) with either
established cardiovascular disease or at least two cardiovascular risk
factors results in a reduction of:
- Renal composite endpoint: Confirmed sustained =40% decrease in
eGFR to eGFR <60 ml/min/1.73m2 and/or ESRD (dialysis =90 days or
kidney transplantation, confirmed sustained eGFR of <15
mL/min/1.73m2) and/or renal or CV death
- All-cause mortality

Primary end point(s): The co-primary outcome variables of the study are the composite
endpoint of cardiovascular death, myocardial infarction, or ischemic
stroke (time to first event) and the composite endpoint of hospitalization
for heart failure or CV death (time to first event). All components of
these composites will be adjudicated.

Secondary Outcome(s)

Secondary end point(s): The secondary outcome variables include:
- Renal composite endpoint: Confirmed sustained =40% decrease in
eGFR to eGFR <60 ml/min/1.73m2 and/or ESRD (dialysis =90 days or
kidney transplantation, confirmed sustained eGFR of <15
mL/min/1.73m2) and/or renal or CV death (time to first event)
- All-cause mortality (time to event)

Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated when the study has been
completed.

Secondary ID(s)

2013-000239-28-GB

D1693C00001

NCT01730534

Source(s) of Monetary Support

AstraZeneca AB