CIN-107

To assess the effect of baxdrostat 2mg versus placebo on ambulatory 24-hour average SBP at 12 weeks

Change in LVMi (g/m\^2), measured by cardiac magnetic resonance imaging (cMRI) from baseline to 12 months of treatment with baxdrostat compared to placebo.

To assess the effect of baxdrostat versus placebo on seated Systolic Blood Pressure (SBP) at Week 8

To assess the effect of baxdrostat vs placebo on achieving normalization of renin at week 8, in participants with dysregulated renin at baseline

Time to first occurrence of any of the components of the composite of: * Hospitalisation for HF * HF without hospitalisation * CV death

Time to the first occurrence of any of the components of the composite of: Kidney disease progression * ≥ 50% sustained decline in eGFR * Onset of kidney failure: * Sustained eGFR \< 15 mL/min/1.73 m2 or * Chronic dialysis treatment or * Receiving a kidney transplant or * Death with a renal primary cause (death due to kidney failure when dialysis is not given) CV events * HF with or without hospitalisation * CV death

To assess the effect of 2 mg baxdrostat versus placebo on seated SBP at Week 12

Change from baseline in eGFR to post treatment.

To assess the effect of 2 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed.

To assess the effect of 1 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed.

Change from baseline in UACR

The primary endpoint is individual participant's cortisol levels at each timepoint. Number of participants with normal stimulated serum total cortisol level at baseline are presented here. Characterisation of the serum total cortisol levels before and after ACTH stimulation test. An ACTH stimulation test using 250 μg ACTH was performed at baseline and Week 8 (End of Treatment), with serum cortisol level measured before and after ACTH stimulation test. Normal cortisol levels are defined as at least 18 μg/dL when measured 60 minutes (±10 minutes) after stimulation. If the Week 8 results show abnormal levels, a repeat test is conducted. In this repeat test, cortisol is considered abnormal only if both of the following conditions are met: the level is less than 14.8 μg/dL at 30 minutes (± 5 minutes) and less than 18 μg/dL at 60 minutes (±10 minutes).

Mean change in seated SBP from baseline to Week 26 of pooled CIN-107 and placebo was assessed.

An AE was defined as any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and/or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational medicinal product, whether or not related to the investigational medicinal product. Any medical condition already present at enrollment should be recorded as medical history and not be reported as an AE unless the medical condition or signs or symptoms present at baseline changes in severity, frequency, or seriousness at any time during the study. In this case, it was be reported as an AE.

For this study, AESIs include the following: Events of hypotension that require clinical intervention; Abnormal potassium laboratory values that require clinical intervention; and Abnormal sodium laboratory values that require clinical intervention.

An AE was or adverse reaction is considered serious if, in the view of either the Investigator or Sponsor, it results in any of the following outcomes: Death, a life-threatening AE, a persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event.

Mean change from baseline at Week 52 in serum potassium (mmol/L).

Mean change from baseline at Week 52 in serum sodium (mmol/L).

Change from baseline at 52 weeks in body weight (kg)

Change from baseline at 52 weeks in temperature (C)

Change from baseline at 52 weeks in seated heart rate (beats/min)

Safety and tolerability will be assessed by comparison of number of treatment emergent adverse events between groups.

AUC \[0 to 24 hours, 0 to last quantifiable concentration, and 0 to infinity of baxdrostat\] will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

Cmax will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

Plasma aldosterone levels will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

Tmax will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

Terminal elimination half-life will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

Measurement of total radioactivity recovery in urine and feces to determine the routes, rates of elimination, and mass balance of total radioactivity from \[14C\] baxdrostat.

Area under the curve (AUC)0-∞ and AUC0-last will be determined for baxdrostat and CIN-107M in plasma.

Determining cumulative amount of baxdrostat and CIN-107M excreted in urine, clearance of baxdrostat and CIN-107M, and fraction of dose excreted renally (baxdrostat only).

Cmax will be determined based on measurement of baxdrostat and CIN-107M in plasma.

Tmax will be determined based on measurement of baxdrostat and CIN-107M in plasma.

t1/2 for baxdrostat and CIN-107M in plasma will be determined based on measurement of baxdrostat and CIN-107M in plasma.

The safety and tolerability of baxdrostat was assessed throughout the study based on incidence of treatment emergent adverse events (AEs), following administration of a single oral dose of baxdrostat to subjects with varying degrees of hepatic function.

Measurement of plasma concentrations of baxdrostat and its major metabolite CIN-107-M. AUC \[0 to 24 hours, 0 to last quantifiable concentration, and 0 to infinity of baxdrostat\] will be determined for baxdrostat and the CIN-107M metabolite.

Cmax will be determined for baxdrostat and the CIN-107M metabolite

Tmax will be determined for baxdrostat and the CIN-107M metabolite

Terminal elimination half-life will be determined for baxdrostat and the CIN-107M metabolite

This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit.

This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit.

This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit.

This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit.

This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit.

This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit.

This PK parameter will be determined for CIN-107 using plasma concentration data.

This PK parameter will be determined for CIN-107 using plasma concentration data.

This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)

Calculated as Ae/AUC. This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)

This PK parameter will be calculated using the urine concentrations of CIN-107

This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.

This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.

This plasma PK parameter will be determined for metformin.

This plasma PK parameter will be determined for metformin.

This plasma PK parameter will be determined for metformin.

This plasma PK parameter will be determined for metformin.

This plasma PK parameter will be determined for metformin.

This plasma PK parameter will be determined for metformin.

This urine PK parameter will be determined for metformin.

This urine PK parameter will be determined for metformin.

This urine PK parameter will be determined for metformin.

The safety and tolerability of CIN-107 will be assessed throughout the study based on quantitation of adverse events that occur following oral doses of CIN-107 tablet and oral solution.

Cmax will be determined for CIN-107 and any other measured metabolites for participants given each formulation of baxdrostat; relative bioavailability will be evaluated by comparing these parameters between patients given the solution versus the tablet.

Cmax will be determined for CIN-107 and any other measured metabolites for participants given baxdrostat under fed versus fasted conditions; food effect will be evaluated by comparing Cmax between participants under each condition.

Area under the curve (AUC)0-∞ and AUC0-last will be determined for baxdrostat and any other measured metabolites for participants given each formulation of baxdrostat. Then relative bioavailability will be evaluated by comparing these AUC parameters between patients given the solution versus the tablet.

Tmax will be determined for CIN-107 and any other measured metabolites for participants given baxdrostat under fed versus fasted conditions, and then food effect will be evaluated by comparing Tmax between participants under each condition.

Area under the curve (AUC)0-∞ and AUC0-last will be determined for CIN-107 and any other measured metabolites for participants given baxdrostat under fed versus fasted conditions, and then food effect will be evaluated by comparing AUC between participants under each condition.

Tmax will be determined for CIN-107 and any other measured metabolites for participants given each formulation of baxdrostat.

This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.

This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.

This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first dose of CIN-107, as the data permit.

This PK parameter will be determined for CIN-107 using plasma concentration data.

This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)

This PK parameter will be calculated using the urine concentrations of CIN-107