Health Condition 1: I509- Heart failure, unspecified
Conditions
Interventions
Intervention1: Baxdrostat/Dapagliflozin: Formulation: Tablet
Dose strength: Baxdrostat 1 mg/2 mg and dapagliflozin 10 mg
Route: Oral
Frequency: once daily
The anticipated total study duration is a
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Age 1 Participants of any sex and gender must be greater than or equal to 40 years old at the time of signing the informed consent. Type of Participant and Disease Characteristics 2 Diagnosed with T2DM and requiring treatment 3 Established CV disease (ischaemic heart disease, cerebrovascular disease, peripheral arterial disease) 4 History of HTN and an SBP greater than or equal to 130 mmHg at screening and greater than or equal to 120 mmHg at the Randomisation Visit. 5 Central laboratory serum potassium must meet the following criteria at the Screening Visit, based on screening eGFR: - for participants with screening eGFR greater than or equal to 45 mL/min/1.73 m2, potassium must be greater than or equal to 3.0 and less than or equal to 4.8 mmol/L at the Screening Visit - for participants with screening eGFR less than 45 mL/min/1.73 m2, potassium must be greater than or equal to 3.0 and less than or equal to 4.5 mmol/L at the Screening Visit 6 At least one additional risk factor for HF: - Age greater than or equal to 70 years - UACR greater than 20 mg/g - eGFR less than 60 mL/min/1.73 m2 - History of polyvascular disease (at least two of: ischaemic heart disease, - cerebrovascular disease, and peripheral arterial disease) - History of atrial fibrillation or atrial flutter - NT-proBNP greater than 125 ng/L Sex and Contraceptive/Barrier Requirements 7 Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Female Participants 8 Female participants not of childbearing potential are defined as participants who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Participants will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomisation without an alternative medical cause. The following age specific requirements apply: (a) Female participants less than 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range. (b) Female participants greater than or equal to 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment. 9 Female participants of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Females of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, from enrolment throughout the study and until at least 4 weeks after last dose of study intervention. Cessation of contraception after this point should be discussed with a responsible physician. (a) The following are not acceptable methods of contraception: periodic abstinence (calendar, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study intervention, withdrawal (coitus interruptus)
Exclusion criteria
Exclusion criteria: Medical Conditions 1 Previously confirmed diagnosis and treatment of heart failure 2 An eGFR less than 30 mL/min/1.73 m2 at screening 3 Known hyperkalaemia, defined as potassium greater than or equal to 5.5 mmol/L within 3 months prior to screening 4 Type 1 diabetes mellitus or uncontrolled T2DM with HbA1c greater than 10.5% (greater than 91 mmol/mol) at screening 5 Serum sodium less than 135 mmol/L at screening, determined as per central laboratory assessment 6 Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, carotid angioplasty, or cardiac surgery, within 3 months prior to randomisation 7 Myocardial infarction within 3 months prior to randomisation, or within 1 month prior to randomisation when there is no further planned revascularisation 8 Percutaneous coronary intervention within 1 month prior to randomisation 9 Known severe hepatic impairment, defined as Child-Pugh Class C, based on records that confirm documented medical history 10 Documented history of adrenal insufficiency 11 Any dialysis (including for acute kidney injury) within 3 months prior to screening 12 Any acute kidney injury within 3 months prior to screening 13 History or known allergy/hypersensitivity to the study treatment, as judged by the Investigator (eg, SGLT2i or active substance or excipients) 14 History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant) 15 Any clinical condition requiring systemic immunosuppression therapy other than maintenance therapy (stable for at least 3 months prior to screening) 16 Drug or alcohol abuse that in the Investigator s judgement makes the participant a poor candidate for the study Prior/Concomitant Therapy 17 Any use of mineralocorticoid receptor antagonists (such as spironolactone, eplerenone, or finerenone) or aldosterone synthase inhibitor within 4 weeks prior to screening and/or during the study 18 Concomitant therapy with strong inducers of cytochrome P450 (CYP) 3 A (eg, apalutamide, avasimibe, carbamazepine, enzalutamide, lumacaftor, mitotane, phenytoin, rifampin, rifapentine, St. John s wort) 19 Use of potassium-sparing diuretics (such as triamterene or amiloride) and direct renin inhibitor (eg, aliskiren) at the time of screening 20 Use of potassium binders (such as sodium zirconium cyclosilicate, patiromer, or sodium polystyrene sulfonate) within 4 weeks prior to screening Other Exclusions 21 Any other condition or therapy, in the judgement of the Investigator or the Sponsor, which would make the participant unsuitable for this study, including a condition or therapy which the Investigator anticipates will not allow participation for the full planned study period (eg, active malignancy or other condition limiting life expectancy to less than 12 months) 22 Participation in another clinical study with an investigational product administered in the last 3 months prior to randomisation 23 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca personnel and/or site personnel) 24 For WOCBP, positive pregnancy test and/or breastfeeding at screening Lifestyle Considerations Meals and Dietary Restrictions Generally, no dietary restric
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine if baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of an HF event or CV deathTimepoint: Time to first occurrence of any of the components of the composite of: - Hospitalisation for HF - HF without hospitalisation - CV death | — |
Secondary
| Measure | Time frame |
|---|---|
| To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of hospitalisation for HF or CV deathTimepoint: Time to first occurrence of any of the components of the composite of: - Hospitalisation for HF - CV death ;To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of HF eventsTimepoint: Time to first occurrence of any of the components of the composite of: - Hospitalisation for HF - HF without hospitalisation ;To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of CV deathTimepoint: Time to CV death;To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of all-cause mortalityTimepoint: Time to all-cause death;To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of stroke or CV deathTimepoint: Time to first occurrence of any of the components of the composite of: - Stroke - CV death ;To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of atrial fibrillation or CV death in participants without history of atrial fibrillation at baselineTimepoint: Time to first occurrence of any of the components of the composite of: - New diagnosis of atrial fibrillation - CV death ;To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of MI or CV deathTimepoint: Time to first occurrence of any of the components of the composite of: - MI - CV death | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, France, Germany, Greece, Hungary, India, Ireland, Italy, Japan, Malaysia, Mexico, Netherlands, Peru, Philippines, Poland, Republic of Korea, Romania, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States of America, Viet Nam
Contacts
Public ContactTapankumar M Shah
AstraZeneca Pharma India Ltd
Outcome results
None listed