A study to evaluate if dapagliflozin can prevent the gradual loss of kidney function and improve survival for patients with chronic kidney disease.

• Register: EUCTR
• Last refreshed on: 29 June 2020
• Main ID: EUCTR2016-003896-24-HU
• Date of registration: 19/12/2016
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A study to evaluate if dapagliflozin can prevent the gradual loss of kidney function and improve survival for patients with chronic kidney disease.
• Scientific title: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease - DAPA CKD
• Date of first enrolment: 08/02/2017
• Target sample size: 4000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003896-24
• 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): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Canada, China, Denmark, Germany, Hungary, India, Korea, Republic of, Mexico, Peru, Philippines, Poland, Russian Federation, Spain, Sweden, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Information center
• Affiliation: AstraZeneca

• Name: Information center
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion criteria:
• Provision of signed informed consent prior to any study specific procedures

• Female or male aged =18 years at the time of consent

• eGFR =25 and =75 mL/min/1.73m2 (CKD-EPI Formula)

• UACR =200 and =5000 mg/g at visit 1

• Stable, and for the patient maximum tolerated labelled daily dose, treatment with ACE-I or ARB for at least 4 weeks before visit 1, if not medically contraindicated
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 2000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2000

Exclusion criteria:
• Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or ANCA-associated vasculitis

• Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment

• History of organ transplantation

• Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor

• Type 1 diabetes mellitus

• New York Heart Association (NYHA) class IV Congestive Heart Failure at the time of enrolment

• MI, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment








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

Health Condition(s) or Problem(s) studied

Chronic kidney disease (CKD)

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: Forxiga
Product Name: Dapagliflozin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DAPAGLIFLOZIN PROPANEDIOL
CAS Number: 960404-48-02
Other descriptive name: DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Forxiga
Product Name: Dapagliflozin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DAPAGLIFLOZIN PROPANEDIOL
CAS Number: 960404-48-2
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)

Secondary Objective: 1) To determine whether dapagliflozin compared with placebo will result in a reduction of the incidence of the composite endpoints of worsening of renal function

2) To determine whether dapagliflozin compared with placebo will result in a reduction of the incidence of the composite endpoint of CV death or hospitalization for heart failure

3) To determine whether dapagliflozin compared with placebo will result in a reduction of the incidence of all-cause mortality


4) Safety Objective: To evaluate the safety and tolerability of dapagliflozin in this patient population

Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated when at least 100% of the primary events are adjudicated, which means at 681 adjudicated primary events.

Primary end point(s): Time to the first occurrence of any of the components of this composite:
1. =50% sustained decline in eGFR
2. Reaching ESRD
? - Sustained eGFR <15 mL/min/1.73m2 or,
? - Chronic dialysis treatment or,
? - Receiving a renal transplant
3. CV death
4. Renal death

Main Objective: To determine if dapagliflozin is superior to placebo in reducing the incidence of the primary composite endpoint of =50% sustained decline in estimated glomerular filtration rate (eGFR), reaching end stage renal disease (ESRD), CV or renal death when added to current background therapy in patients with eGFR =25 and =75 mL/min/1.73m2 and albuminuria (urine albumin creatinine ratio [UACR] =200 and =5000 mg/g)

Secondary Outcome(s)

Secondary end point(s): 1) Time to the first occurrence of any of the components of this composite:
1. =50% sustained decline in eGFR
2. Reaching ESRD
3. Renal death

2) Time to the first occurrence of either of the components of this composite:
1. CV death
2. Hospitalization for heart failure

3) Time to death from any cause

4) Safety endpoints:
1. Serious adverse event (SAE)
2. Discontinuation of investigational product (IP) due to adverse event (DAE)s
3. Changes in clinical chemistry/haematology parameters
4. AEs of interest (volume depletion, renal events, major hypoglycaemic events, fractures, diabetic ketoacidosis (DKA) and AEs leading to amputation)

Timepoint(s) of evaluation of this end point: Secondary endpoints will only be evaluated once – and that is when the study stops, when at least 100% of the primary events are adjudicated.

Secondary ID(s)

D169AC00001

2016-003896-24-SE

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 26/01/2017
Contact: