A Study of CIN-107 in Patients With Uncontrolled Hypertension

Study Overview
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Brief Summary
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This is a Phase 2, randomized, multicenter study to evaluate the efficacy and safety of multiple dose strengths of baxdrostat (also called CIN-107) in the treatment of patients with uncontrolled hypertension. The primary objective was to demonstrate that treatment with baxdrostat for 8 weeks would lower the systolic blood pressure (SBP) in patients who were hypertensive despite taking one or two anti-hypertensive medications. Participants were assigned to take placebo or baxdrostat once per day for 8 weeks while they continued taking the regular anti-hypertensive medications. At the end of the 8-week period, qualified patients could participate in Part II of the study and receive 2 mg baxdrostat for 4 weeks while they discontinued taking the background anti-hypertensive medication.

Official Title
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A Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Multiple Dose Strengths of CIN-107 as Compared to Placebo After 8 Weeks of Treatment in Patients With Uncontrolled Hypertension

Conditions
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Uncontrolled Hypertension

Intervention / Treatment
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* Drug: CIN-107
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is on a stable regimen of background antihypertensive agent(s) for at least 8 weeks and would be considered a candidate for an additional antihypertensive agent at the time of screening ; Has a mean seated systolic blood pressure (SBP) ≥ 140 mmHg or ≥ 130 mmHg if diabetic; Demonstrates ability to be adherent to the study drug and their anti-hypertensive medication during a run-in period If taking an SGLT2 inhibitor, the regimen must be stable for at least 8 weeks prior to randomization; and Agrees to comply with the contraception and reproduction restrictions of the study; Exclusion Criteria: Has a mean seated systolic blood pressure (SBP) ≥180 mmHG; Has a body mass index (BMI) >50 kg/m2; Is using alpha or beta blockers for any primary indication other than systemic hypertension (eg, migraine headache); Is not willing or not able to discontinue an MRA or potassium sparing diuretic as part of an existing antihypertensive regimen; Has documented estimated eGFR <30 mL/min/1.73m2; Has known and documented New York Heart Association stage III or IV chronic heart failure; Has had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure within 6 months before screening; Major cardiac surgery within 6 months before Screening; Has chronic permanent atrial fibrillation; Has uncontrolled diabetes with glycated hemoglobin >10% at Screening; Has planned dialysis or kidney transplantation planned during the course of the study; Prior solid organ transplant and/or cell transplants; Sodium <130 mEq/L; Potassium <3.5 mEq/L; Potassium >5 mEq/L; White blood cell count >15 × E9/L or absolute neutrophil count <1 × E9/L at Screening; Is positive for HIV antibody, hepatitis C virus RNA, or hepatitis B surface antigen; Has typical consumption of ≥14 alcoholic drinks weekly;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CIN-107 0.5 mg<br>Remain on background anti-hypersensitive regimen for 8 weeks. After 8 weeks, patient will receive the highest dose of CIN-107 (2 mg) and discontinue their background antihypertensive agent(s) for 4 weeks | Drug: CIN-107<br>* CIN-107 tablets by mouth once daily<br>* Other names: Baxdrostat;|
| Experimental: CIN-107 1 mg<br>Remain on background anti-hypersensitive regimen for 8 weeks. After 8 weeks, patient will receive the highest dose of CIN-107 (2 mg) and discontinue their background antihypertensive agent(s) for 4 weeks | Drug: CIN-107<br>* CIN-107 tablets by mouth once daily<br>* Other names: Baxdrostat;|
| Experimental: CIN-107 2 mg<br>Remain on background anti-hypersensitive regimen for 8 weeks. After 8 weeks, patient may remain on CIN-107 (2 mg) and discontinue their background antihypertensive agent(s) for 4 weeks or withdraw study participation depending on BP control | Drug: CIN-107<br>* CIN-107 tablets by mouth once daily<br>* Other names: Baxdrostat;|
| Placebo Comparator: Placebo<br>Remain on background anti-hypersensitive regimen for 8 weeks. After 8 weeks, patient will receive the highest dose of CIN-107 (2mg) and discontinue their background antihypertensive agent(s) for 4 weeks | Drug: Placebo<br>* Placebo tablets by mouth once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Seated Systolic BP (SBP) | The primary efficacy endpoint was the change from baseline in mean seated SBP after 8 weeks of treatment in patients with uncontrolled HTN (Part 1). | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Seated Diastolic BP (DBP) | The change from baseline in mean seated DBP with CIN-107 compared to placebo after 8 weeks of treatment (Part 1) | 8 weeks | 
| Change From Baseline in 24-hour Urine Aldosterone | The change from baseline in 24-hour urine aldosterone levels with CIN 107 compared to placebo after 8 weeks of treatment (Part 1) | 8 weeks | 
| Change From Baseline in 24-hour Serum Aldosterone | The change from baseline in 24-hour serum aldosterone levels with CIN 107 compared to placebo after 8 weeks of treatment (Part 1) | 8 weeks | 
| Percentage of Patients Achieving a Mean Seated SBP <130 mmHg | The percentage of patients achieving a mean seated SBP <130 mmHg (responders) with CIN-107 compared to placebo after 8 weeks of treatment (Part 1; Weeks 1 to 8) | 8 weeks | 
| Change From Baseline in 24-hour Urine Renin | The change from baseline in 24-hour urine renin levels with CIN-107 compared to placebo after 8 weeks of treatment (Part 1) | 8 weeks | 
| Change From Baseline in 24-hour Serum Renin | The change from baseline in 24-hour serum renin levels with CIN-107 compared to placebo after 8 weeks of treatment (Part 1) | 8 weeks |