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.
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, defined as BP targets not being achieved in an individual despite a stable regimen of ≥2 antihypertensive agents from different therapeutic classes (at full doses per guidelines or maximum tolerated dose in the judgement of the Investigator), none of which is a diuretic. 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. The study is planned to be conducted in approximately 50 study sites across China. A Data Monitoring Committee will be appointed for this study to monitor the safety and scientific integrity of a human research intervention and to make recommendations to AstraZeneca regarding the stopping of a study due to any harm. An Executive Committee will be formed to provide scientific oversight and confirmation of the overall study design, of CSP and any protocol amendments (If appliable).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
286
baxdrostat 2mg tablet administered orally, once daily (QD).
Placebo 2mg tablet administered orally, once daily (QD).
Change from baseline in ambulatory 24-hour average Systolic blood pressure(SBP) at Week 12
To assess the effect of baxdrostat 2mg versus placebo on ambulatory 24-hour average SBP at 12 weeks
Time frame: Week12
Change from baseline in ambulatory night-time average Systolic blood pressure(SBP) at Week 12
To assess the effect of baxdrostat 2mg versus placebo on ambulatory night-time average SBP at 12 weeks
Time frame: week12
Change from baseline in ambulatory daytime average Systolic blood pressure(SBP) at Week 12
To assess the effect of baxdrostat 2mg versus placebo on ambulatory daytime average Systolic blood pressure(SBP) at 12 weeks
Time frame: week12
Change from baseline in seated Systolic blood pressure(SBP) at Week 12
To assess the effect of baxdrostat 2mg versus placebo on seated SBP at 12 weeks
Time frame: week12
Percentage achieving ambulatory 24-hour average SBP <130 mmHg at Week 12
To assess the effect of baxdrostat 2mg versus placebo on achieving ambulatory 24-hour average SBP \<130 mmHg at 12 weeks
Time frame: week12
Change from baseline in ambulatory 24-hour Diastolic Blood Pressure(DBP) at Week 12
To assess the effect of baxdrostat 2mg versus placebo on ambulatory 24-hour DBP at 12 week
Time frame: week12
Change from baseline in ambulatory night-time average DBP at Week 12
To assess the effect of baxdrostat 2mg versus placebo on ambulatory night-time average DBP at 12 weeks
Time frame: week12
Change from baseline in ambulatory daytime average DBP at Week 12
To assess the effect of baxdrostat 2mg versus placebo on ambulatory daytime average DBP at 12 weeks
Time frame: week12
Change from baseline in seated DBP at Week 12
To assess the effect of baxdrostat 2mg versus placebo on seated DBP at 12 weeks
Time frame: week12
Adverse Events (AE)s
To assess the safety and tolerability of baxdrostat
Time frame: ICF to safety followup visit-approximately 22 weeks.
Adverse Events of special interest (AESI)s -hyperkalaemia
To assess the safety and tolerability of baxdrostat
Time frame: ICF to safety followup visit-approximately 22 weeks.
Serious Adverse Event(SAE)s
To assess the safety and tolerability of baxdrostat
Time frame: ICF to safety followup visit-approximately 22 weeks.
Discontinuation of IP due to Adverse Event(DAE)s
To assess the safety and tolerability of baxdrostat
Time frame: ICF to safety followup visit-approximately 22 weeks.
Adverse Events of special interest (AESI)s- hyponatraemia
To assess the safety and tolerability of baxdrostat
Time frame: ICF to safety followup visit-approximately 22 weeks.
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