This is a Phase IIIb, multicentre, randomised, double-blind, placebo-controlled, parallel group study to evaluate the effect of baxdrostat 2mg versus placebo, administered QD orally, on the reduction of ambulatory 24-hour average SBP in participants with uHTN.
Consenting participants will be screened within 4 weeks and will subsequently enter a 4-week run-in period with placebo. Thereafter, participants will be randomised in a 1:1 ratio to receive one of the following 2 treatments QD, during a 12-week double-blind treatment period:
baxdrostat 2mg Placebo The randomisation will be stratified by mean ambulatory SBP at baseline (\<140 mmHg, ≥140 mmHg) and the number of background antihypertensive medication classes (2, ≥3) at baseline.
During the 12-week double-blind treatment period, participants should remain on their background antihypertensive medication. Doses of background medications should not be changed during this period unless participants experience SBP \< 100 mmHg with symptoms of hypotension. Rescue therapy is permitted if the SBP or DBP exceeds 170 or 105 mmHg, respectively. The choice of rescue therapy is based on the Investigator's best clinical judgement; however, the use of potassium-sparing diuretics and MRAs are prohibited.After completing the 12 weeks double-blind treatment period participants will complete a 2-week safety follow-up period. The total duration of study participation will be of approximately 22 weeks.
Mean seated SBP on AOBPM ≥140 mmHg and <170 mmHg at screening. Seated BP will be measured using standardised automated BP machines and using standardised procedures.
Have a stable regimen (≥ 4 weeks before the screening visit) of ≥ 2 antihypertensive medications, from different therapeutic classes (should not be a diuretic), at full doses per guidelines or maximum tolerated doses in the judgement of the Investigator, for at least 4 weeks prior to screening (participants who do not meet this criterion may be rescreened at the Investigator's discretion. Beta blockers used to treat other conditions (i.e., migraine, heart failure [HF], coronary artery disease) should not be counted as an antihypertensive medication for the purpose of qualifying for this study.
Have eGFR ≥45 mL/min/1.73m2 at screening.
Serum potassium (K+) level ≥3.5 and <5.0 mmol/L at screening, determined as per central laboratory.
As judged by the investigator, any evidence of which in the investigator's opinion makes it undesirable for the participant to participate in the study.
Mean seated SBP on AOBPM ≥170 mmHg (participants who do not meet this criterion may be rescreened at the Investigator's discretion, see Section 5.4.2 for rescreening criteria and Section 8.2.1 for BP measurement procedures).
Mean seated DBP on AOBPM ≥110 mmHg (participants who do not meet this criterion may be rescreened at the Investigator's discretion).
Serum sodium level (Na+) <135 mmol/L at screening, determined as per central laboratory.
AstraZeneca
Lead sponsor
Tigermed Consulting Co., Ltd
Collaborator