Overview
The purpose of the study is to evaluate the efficacy, safety and tolerability of balcinrenone/dapagliflozin compared with dapagliflozin alone on patients with chronic kidney disease (CKD) and albuminuria. This study will evaluate the effect of the balcinrenone/dapagliflozin on urinary albumin-to-creatinine ratio (UACR), compared with dapagliflozin in patients with CKD. This is a dose-finding study aiming to identify an optimal dose of balcinrenone/dapagliflozin for a future Phase III study in patients with CKD.
Description
This is a Phase IIb, multicentre, randomised, double-blind, dose-finding, parallel group, double-dummy study aiming to determine the effect on albuminuria, as well as safety and tolerability, of balcinrenone/dapagliflozin compared with dapagliflozin, when given once daily on top of other Standard of Care (SoC) to patients with CKD and albuminuria.
Study population will include participants with CKD (eGFR ≥ 25 to < 60 mL/min/1.73 m2) and UACR > 100 mg/g to ≤ 5000 mg/g. Participants with or without a diagnosis of T2DM and with or without an SGLT2 inhibitor treatment at screening are eligible for the study.
The study will be conducted at approximately 110 sites in approximately 16 countries globally.
At least 300 participants will be randomised in order to have 300 evaluable participants.
Participants will be randomised to one of 3 treatment arms in a 1:1:1 ratio:
- Balcinrenone/dapagliflozin 15 mg/10 mg
- Balcinrenone/dapagliflozin 40 mg/10 mg
- Dapagliflozin 10 mg
For each participant, the total duration of participation will be approximately 23 weeks: an up to 3-week screening period followed by a 12-week treatment period, and an 8-week follow-up period after end of investigational medicinal product (IMP) treatment.
Eligibility
Inclusion Criteria:
- Age ≥ 18 years old
- Diagnosis of CKD and eGFR ≥ 25 to < 60 mL/min/1.73 m2.
- UACR > 100 mg/g (10 mg/mmol) to ≤ 5000 mg/g (500 mg/mmol).
- Serum potassium ≥ 3.5 mmol/L to ≤ 5.0 mmol/L.
- Stable RAAS inhibitors treatment for 4 weeks before screening. Participants who cannot tolerate or are not treated with RAAS inhibitors can also participate in the study.
Exclusion criteria:
- Uncontrolled arterial hypertension (SBP > 160 mmHg or DBP > 100 mmHg).
- Hypotension defined as SBP < 100 mmHg.
- Autosomal dominant polycystic kidney disease, lupus nephritis or ANCA-associated vasculitis or other nephropathies that are unstable or progress rapidly.
- Cytotoxic or immunomodulatory therapy within 6 months prior to screening, or current, or planned within 6 months following randomization.
- History of solid organ or bone marrow transplantation
- Recent (90 d prior to screening) or ongoing dialysis, or likely need for dialysis within 3 months following randomization.
- Myocardial infarction, acute coronary syndrome, stroke or transient ischaemic attack within the previous 12 weeks.
- Type 1 diabetes mellitus (DM) or uncontrolled type 2 DM.
- Hepatic disease, including active hepatitis, and/or hepatic impairment (Child-Pugh class B-C; or any of AST or ALT > 3 × ULN; or TBL > 2 × ULN.
- Serum HCO3 < 18 mmol/L at screening.
- Adrenal insufficiency (eg, Addison's disease, prolonged use of glucocorticoids).
- Any use of the following within 4 weeks prior to screening:
- MRA (or planned initiation of MRA treatment), potassium sparing diuretic, potassium binders, fludrocortisone.
- Strong or moderate CYP3A4 inducers or inhibitors prohibited at least 1 week prior to randomisation and during treatment.