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: 28 February 2019
• Main ID: EUCTR2013-000239-28-CZ
• Date of registration: 03/05/2013
• 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, DoubleBlind, PlaceboControlled 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: 19/06/2013
• 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, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Philippines, Poland, Romania, 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 runin)
2. Female or male aged = 40 years
3. Diagnosed with T2DM 4. High Risk for CV event defined as having either established CV disease and/or multiple risk factors: Established
CV Disease 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
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 7850

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 runin 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 nonmelanoma 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 noncardiovascular 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 breastfeeding patients Patients will be excluded during runin and should not be randomized if the following
are observed from laboratory or observation during enrollment and runin 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 CockroftGault 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: LLT Classification code 10012613 Term: Diabetes mellitus non-insulin-dependent System Organ Class: 100000072461

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)

Primary end point(s): The coprimary 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.

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 Allcause
mortality

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

Secondary Outcome(s)

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

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) Allcause mortality (time to event)

Secondary ID(s)

D1693C00001

NCT01730534

2013-000239-28-GB

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 25/09/2019
• Date Completed: 16/09/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000239-28/results