Health Condition 1: I169- Hypertensive crisis, unspecified
Conditions
Interventions
Intervention1: Baxdrostat 1 mg or 2 mg or Placebo: Treatment period – Randomization double blind
Participants will be randomised in a 1:1:1 ratio to receive 1 of the following 3 treatments QD, during
Participants who received placebo will be randomised in a 1:4 ratio to receive either 2 mg
baxdrostat, orally QD during a 12-week open-label period (from Week 12 to Week 24).
Control Intervention1: P
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion Criteria Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Male or female participants must be = 18 years old., at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. Mean siSBP on automated office blood pressure measurement, AOBPM = 140 mmHg and less than 170 mmHg at Screening. See Section 8.2.1 for BP measurement procedures. 3. Fulfil at least 1 of the following 2 criteria: (a) Participants with uHTN: have a stable regimen (= 4 weeks before the screening visit) of 2 antihypertensive medications, from different therapeutic classes (at least one should be a diuretic), at maximum tolerated dose in the judgement of the Investigator (participants who do not meet this criterion may be rescreened at the Investigator s discretion, see Section 5.4.1). Beta blockers used to treat other conditions (ie, migraine, HF, coronary artery disease) should not be counted as an antihypertensive medication for the purpose of qualifying for this study. (b) Participants with rHTN: have a stable regimen (= 4 weeks before the screening visit) of = 3 antihypertensive medications, from different therapeutic classes (at least one should be a diuretic), at maximum tolerated dose in the judgement of the Investigator (participants who do not meet this criterion may be rescreened at the Investigator s discretion, see Section 5.4.1). Beta blockers used to treat other conditions (ie, migraine, HF, coronary artery disease) should not be counted as an antihypertensive medication for the purpose of qualifying for this study. 4. Estimated glomerular filtration rate = 45 mL/min/1.73m2 at Screening (using the eGFR equation developed by Inker et al, 2021). 5. Serum potassium (K+) level = 3.5 and less than 5.0 mmol/L at Screening, determined as per central laboratory (participants who have serum K+ levels less than 3.5 mmol/L may be rescreened at the Investigator s discretion, see Section 5.4.1). Sex and Contraceptive/Barrier Requirements 6. For female participants: Contraceptive used by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. (a) Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Females 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: (b) Females less than 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range. (c) Females = 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment. (d) 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 p
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. As judged by the Investigator, any evidence which in the Investigator s opinion makes it undesirable for the participant to participate in the study. 2. Mean siSBP 1 on AOBPM = 170 mmHg at randomisation (participants who do not meet this criterion may be rescreened at the Investigator s discretion, see Section 5.4.1 for rescreening criteria and Section 8.2.1 for BP measurement procedures). 3. Mean siDBP 2 on AOBPM = 105 mmHg at randomisation (participants who do not meet this criterion may be rescreened at the Investigator s discretion, see Section 5.4.1). 4. Simultaneous use of ACEIs, ARBs or ARNI in current or prior treatment (within the 4 weeks before screening). 5. Serum sodium (Na+) level less than 135 mmol/L at Screening, determined as per central laboratory. 6. Has the following known secondary causes of hypertension: renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, pheochromocytoma, Cushing s syndrome, aortic coarctation. 7. New York Heart Association functional HF class IV at Screening. 8. Medical history of hospitalisation for HF, acute coronary syndrome, stroke or hypertensive encephalopathy within 6 months prior to Screening. 9. Medical history of percutaneous coronary intervention/coronary artery bypass grafting within 6 months prior to Screening, or planned percutaneous coronary intervention/coronary artery bypass grafting. 10. Known current severe left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease. 11. Participants suspected to have severe cardiac hypertrophy. 12. Left bundle branch block, persistent atrial fibrillation or any cardiac arrhythmia requiring treatment. 13. Have a Screening QTcF value greater than 470 msec. 14. Family history of Long QT syndrome. 15. Heart rate less than 45 or greater than 110 beats/min in a resting position, as per vital signs assessment. 16. Known severe hepatic impairment, defined as Child-Pugh Class C, based on records that confirm documented medical history. 17. Uncontrolled diabetes with HbA1c greater than 10.0% (86 mmol/mol) at Screening. 18. Participants with a diagnosis of adrenal insufficiency. 19. Participants who are pregnant or breastfeeding. 20. Any of the following related to COVID-19 infection (participants who fail this criterion may be rescreened at the Investigator s discretion, see Section 5.4.1): a) Suspected (at the Investigator s discretion) or confirmed COVID-19 infection within the last 4 weeks prior to Screening or at Baseline. b) Hospitalisation for COVID-19 within the last 12 weeks prior to Screening. Prior/Concomitant Therapy 21. Prior medical treatment with any MRAs, potassium-sparing diuretic, direct renin inhibitor, or antiarrhythmic medications used within 4 weeks prior to Screening. 22. Is expected to receive or is receiving systemic corticosteroids (eg, prednisone, prednisolone, dexamethasone), systemic immunosuppressants (eg, tacrolimus, cyclosporin), or chronic (taken more than 3 times a week for more than 3 months) use of NSAIDs. 23. Is expected to receive or is receiving any herbal anti-hyperten
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the effect of 2 mg baxdrostat versus placebo on siSBP at 12 weeksTimepoint: To assess the effect of 2 mg baxdrostat versus placebo on siSBP at 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the effect of 1 mg baxdrostat versus placebo on siSBP at 12 weeks.Timepoint: Change from baseline in siSBP at Week 12.;To assess the effect of 2 mg baxdrostat versus placebo on siSBP at 8 weeks after randomised withdrawal.Timepoint: Change from RWD baseline (Week 24) in siSBP at Week 32. ;To assess the effect of treatment with baxdrostat 2 mg vs placebo on ambulatory 24-hour average SBP at Week 12.Timepoint: Change from baseline in the mean ambulatory 24-hour SBP at Week 12 as measured by ABPM. ;To assess the effect of treatment with baxdrostat 1 mg vs placebo on ambulatory 24-hour average SBP at Week 12.Timepoint: Change from baseline in the mean ambulatory 24-hour SBP at Week 12 as measured by ABPM. ;To assess the effect of 2 mg baxdrostat versus placebo on siDBP at Week 12.Timepoint: Change from baseline in siDBP at Week 12.;To assess the effect of 2 mg baxdrostat versus placebo on achieving siSBP less than 140 mmHg at Week 12.Timepoint: Achieving siSBP less than 140 mmHg at Week 12. ;To assess the effect of 1 mg baxdrostat versus placebo on siDBP at Week 12.Timepoint: Change from baseline in siDBP at Week 12.;To assess the effect of 1 mg baxdrostat versus placebo on achieving siSBP less than 140 mmHg at Week 12.Timepoint: Achieving siSBP less than 140 mmHg at Week 12.;To assess the effect of 2 mg baxdrostat versus placebo on siSBP at Week 12 in the rHTN subgroup.Timepoint: Change from baseline in siSBP at Week 12.;To assess the effect of 1 mg baxdrostat versus placebo on siSBP at Week 12 in the rHTN subgroup.Timepoint: Change from baseline in siSBP at Week 12.;Exploratory To characterise the pharmacokinetics of baxdrostatTimepoint: Concentration of baxdrostat in plasma and PK parameters as data allow. ;To assess the effect of 2 mg baxdrostat versus placebo on siSBP at 4 weeks after randomised withdrawal.Timepoint: Change from RWD baseline (Week 24) in siSBP at Week 28. ;To assess the effect of 2 mg baxdrostat versus placebo on achie | — |
Countries
Argentina, China, Hong Kong, India, Japan, Philippines, Republic of Korea, Turkey, Viet Nam
Contacts
Public ContactTapankumar M Shah
AstraZeneca Pharma India Ltd
Outcome results
None listed