E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease (CKD) |
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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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
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) |
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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 |
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E.2.3 | Trial contains a sub-study | No |
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 |
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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
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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
|
|
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. |
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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) and AEs leading to amputation and AEs leading to risk for lower limb amputations ["preceding events"]). |
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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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 5 |
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 | No |
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 |
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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
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The last visit of the last patient undergoing the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |