Clinical Trials Register

Summary
EudraCT Number:	2016-003896-24
Sponsor's Protocol Code Number:	D169AC00001
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-01-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2016-003896-24

A.3

Full title of the trial

A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and
Cardiovascular Mortality in Patients with Chronic Kidney Disease

Badanie oceniające wpływ dapagliflozyny na punkty końcowe dotyczące nerek i śmiertelność z przyczyn sercowo-naczyniowych u pacjentów z przewlekłą chorobą nerek

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

Badanie oceniające, czy dapagliflozyna może zapobiec stopniowej utracie czynności nerek i wydłużyć przeżycie pacjentów z przewlekła chorobą nerek.

A.3.2

Name or abbreviated title of the trial where available

DAPA CKD

A.4.1

Sponsor's protocol code number

D169AC00001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Information center
B.5.3	Address:
B.5.3.1	Street Address	N/A
B.5.3.2	Town/ city	N/A
B.5.3.3	Post code	N/A
B.5.3.4	Country	United States
B.5.6	E-mail	information.center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Forxiga
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dapagliflozin
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DAPAGLIFLOZIN PROPANEDIOL
D.3.9.1	CAS number	960404-48-02
D.3.9.3	Other descriptive name	DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Forxiga
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dapagliflozin
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DAPAGLIFLOZIN PROPANEDIOL
D.3.9.1	CAS number	960404-48-2
D.3.9.3	Other descriptive name	DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic kidney disease (CKD)

Przewlekła choroba nerek (PChN)

E.1.1.1

Medical condition in easily understood language

Renal Disease: A gradual loss of kidney function leading to insufficient filtration of waste and excess fluid from the blood

Choroba nerek: stopniowa utrata czynności nerek prowadząca do niewystarczającej filtracji krwi ze zbędnych substancji i nadmiaru płynów z krwi.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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)

Określenie przewagi dapagliflozyny nad placebo pod względem redukowania częstości występowania pierwszorzędowego złożonego punktu końcowego, którym jest trwałe obniżenie o ≥50% szacunkowej filtracji kłębuszkowej (eGFR), osiągnięcie stadium schyłkowej choroby nerek (SChN), zgon z przyczyn SN/nerkowych, po dołączeniu do podstawowego leczenia u pacjentów z eGFR ≥25 i ≤75 ml/min/1,73 m2 i albuminurią (stosunkiem albumin do kreatyniny w moczu [UACR] ≥200 i ≤5000 mg/g).

E.2.2

Secondary objectives of the trial

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

1) Określenie, czy dapagliflozyna, w porównaniu z placebo, zmniejsza częstość występowania złożonego punktu końcowego dotyczącego pogorszenia czynności nerek.
2) Określenie, czy dapagliflozyna, w porównaniu z placebo, zmniejsza częstość występowania złożonego punktu końcowego obejmującego zgon z przyczyn SN lub hospitalizację z powodu niewydolności serca
3) Określenie, czy dapagliflozyna, w porównaniu z placebo, zmniejsza ryzyko zgonu z dowolnej przyczyny.
4) Ocena bezpieczeństwa i tolerancji dapagliflozyny u badanej populacji pacjentów.

E.2.3

Trial contains a sub-study

E.3

Principal 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) at visit 1

• Evidence of increased albuminuria 3 months or more before visit 1 and
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

1. Udzielenie pisemnej świadomej zgody przed wykonaniem jakichkolwiek procedur związanych z badaniem.
2. Kobiety lub mężczyźni w wieku ≥18 lat w chwili wyrażania zgody.
3. eGFR ≥25 i ≤75 ml/min/1,73 m2 (wzór CKD-EPI) podczas wizyty 1.
4. Udokumentowany wzrost obecność ciał białkowych w moczu (albuminuria) w okresie 3 miesięcy lub więcej przed wizytą nr 1 i wartość UACR ≥200 i ≤5000 mg/g podczas wizyty 1.
5. Leczenie z zastosowaniem ACE I lub ARB w stabilnej i maksymalnej tolerowanej przez danego pacjenta, zgodnej z drukami informacyjnymi dawce dobowej, przez co najmniej 4 tygodnie przed wizytą 1., o ile nie występują przeciwwskazania medyczne.

E.4

Principal 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

1. Autosomalna dominująca lub autosomalna recesywna torbielowatość nerek, toczniowe zapalenie nerek lub zapalenie naczyń związane z ANCA.
2. Otrzymywanie terapii cytotoksycznej, terapii immunosupresyjnej lub innych form immunoterapii z powodu pierwotnej lub wtórnej choroby nerek w okresie 6 miesięcy przed włączeniem do badania.
3. Przeszczep narządu w wywiadzie.
4. Otrzymywanie leczenia inhibitorem SGLT2 w okresie 8 tygodni przed włączeniem do badania lub wcześniejsze stwierdzenie nietolerancji inhibitora SGLT2.
5. Cukrzyca typu 1 (T1D).
6. Niewydolność serca klasy IV według Nowojorskiego Towarzystwa Kardiologicznego (NYHA) w chwili włączenia do badania (patrz załącznik C).
7. Zawał mięśnia sercowego (MI), niestabilna dławica piersiowa, udar mózgu lub przemijający atak niedokrwienny (TIA) w okresie 12 tygodni przed włączeniem do badania.

E.5 End points

E.5.1

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

Czas do pierwszego wystąpienia któregokolwiek z elementów tego złożonego punktu końcowego:
1. Trwałe obniżenie eGFR o ≥50%.
2. Osiągnięcie stadium SChN
- Utrwalona wartość eGFR
<15 ml/min/1,73 m2 lub
- Przewlekła dializoterapia lub
- Otrzymanie przeszczepu nerki
3. Zgon z przyczyn SN.
4. Zgon z przyczyn nerkowych.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint will be evaluated when at least 681 primary events has been confirmed.

Ocena pierwszorzędowego punku końcowego będzie miała miejsce po potwierdzeniu wystąpienia co najmniej 681 zdarzeń pierwszorzędowych.

E.5.2

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), AEs leading to amputation and AEs leading to risk for lower limb amputations
["precedin events"]).

1) Czas do pierwszego wystąpienia któregokolwiek z elementów tego złożonego punktu końcowego:
1. Trwałe obniżenie eGFR o ≥50%.
2. Osiągnięcie stadium SChN.
3. Zgon z przyczyn nerkowych.
2) Czas do pierwszego wystąpienia któregokolwiek z elementów tego złożonego punktu końcowego:
1. Zgon z przyczyn SN.
2. Hospitalizacja z powodu niewydolności serca.
3) Czas do wystąpienia zgonu z dowolnej przyczyny.
4) Punkty końcowe dotyczące bezpieczeństwa:
1. Poważne zdarzenie niepożądane (SAE).
2. Przerwanie stosowania badanego produktu (IP) z powodu AE (DAE).
3. Zmiany wyników badań biochemicznych/morfologii krwi.
4. Zdarzenia niepożądane (AE) o szczególnym znaczeniu (zmniejszenie objętości osocza, zdarzenia dotyczące nerek, poważne epizody hipoglikemii, złamania, cukrzycowa kwasica ketonowa (DKA) oraz AE prowadzące do amputacji i AE prowadzące do ryzyka amputacji kończyny dolnej [„wydarzenia poprzedzające”]).

E.5.2.1

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 681 primary events has been confirmed.

Drugorzędowe punkty końcowe będą oceniane tylko jeden raz – i ta ocena będzie miała miejsce po zakończeniu badania, kiedy potwierdzone zostanie wystąpienie co najmniej 681 zdarzeń pierwszorzędowych.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarker

biomerker

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

105

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The last visit of the last patient undergoing the study.

Ostatnia wizyta ostatniego pacjenta uczestniczącego w badaniu

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

When applicable a legally representative, together with impartial witness, is allowed to sign the informed consent of behalf of a patient (i.e. illiterate patients).

Przedstawiciel prawny, w obecności 2 bezstronnych świadków, mogą podpisać formularz zgody w imieniu pacjenta (tzn. pacjent niepiśmienny) - jeżeli dotyczy).

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

150

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1040

F.4.2.2

In the whole clinical trial

4000

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Nie dotyczy

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-03-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-02-14

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-06-12

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials