A Study of CIN-107 in Patients With Uncontrolled Hypertension

• CIN-107 (Drug), also known as Baxdrostat: CIN-107 tablets by mouth once daily
• Placebo (Drug): Placebo tablets by mouth once daily

Primary outcomes

• Change From Baseline in Mean Seated Systolic BP (SBP) [8 weeks]: 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).

Secondary outcomes

• Change From Baseline in Mean Seated Diastolic BP (DBP) [8 weeks]: The change from baseline in mean seated DBP with CIN-107 compared to placebo after 8 weeks of treatment (Part 1)
• Change From Baseline in 24-hour Urine Aldosterone [8 weeks]: The change from baseline in 24-hour urine aldosterone levels with CIN 107 compared to placebo after 8 weeks of treatment (Part 1)
• Change From Baseline in 24-hour Serum Aldosterone [8 weeks]: The change from baseline in 24-hour serum aldosterone levels with CIN 107 compared to placebo after 8 weeks of treatment (Part 1)
• Percentage of Patients Achieving a Mean Seated SBP <130 mmHg [8 weeks]: 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)
• Change From Baseline in 24-hour Urine Renin [8 weeks]: The change from baseline in 24-hour urine renin levels with CIN-107 compared to placebo after 8 weeks of treatment (Part 1)
• Change From Baseline in 24-hour Serum Renin [8 weeks]: The change from baseline in 24-hour serum renin levels with CIN-107 compared to placebo after 8 weeks of treatment (Part 1)

Sex: All, ages: 18 Years to any

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;

Participant flow

Outcome results

• Change From Baseline in Mean Seated Systolic BP (SBP) (Primary), Least squares mean, mmHg: Placebo -16.6 +/- 1.58; CIN-107 0.5 mg -17.0 +/- 1.63; CIN-107 1 mg -16.0 +/- 1.62; CIN-107 2 mg -19.8 +/- 1.67
• Change From Baseline in Mean Seated Diastolic BP (DBP) (Secondary), Least squares mean, mmHg: Placebo -5.9 +/- 1.17; CIN-107 0.5 mg -5.8 +/- 1.20; CIN-107 1 mg -5.0 +/- 1.19; CIN-107 2 mg -5.4 +/- 1.23
• Change From Baseline in 24-hour Urine Aldosterone (Secondary), Least squares mean, ng/g: Placebo -19.90 +/- 29.183; CIN-107 0.5 mg -114.16 +/- 31.305; CIN-107 1 mg -140.45 +/- 29.999; CIN-107 2 mg -121.64 +/- 30.760
• Change From Baseline in 24-hour Serum Aldosterone (Secondary), Least squares mean, ng/dL: Placebo -0.70 +/- 0.490; CIN-107 0.5 mg -2.76 +/- 0.493; CIN-107 1 mg -2.95 +/- 0.508; CIN-107 2 mg -2.92 +/- 0.515
• Percentage of Patients Achieving a Mean Seated SBP <130 mmHg (Secondary), Count of participants, Participants: Placebo 36; CIN-107 0.5 mg 36; CIN-107 1 mg 33; CIN-107 2 mg 43
• Change From Baseline in 24-hour Urine Renin (Secondary), Least squares mean, ng/day: Placebo -20.08 +/- 16.584; CIN-107 0.5 mg -6.54 +/- 15.739; CIN-107 1 mg -5.74 +/- 10.703; CIN-107 2 mg 4.11 +/- 17.930
• Change From Baseline in 24-hour Serum Renin (Secondary), Least squares mean, ng/L: Placebo 92.902 +/- 144.3969; CIN-107 0.5 mg 63.565 +/- 195.0495; CIN-107 1 mg 88.041 +/- 91.2996; CIN-107 2 mg -140.961 +/- 151.5431

Adverse events

Time frame: Part I - AEs during the 8-week treatment period Part II - AEs during the following 4-week treatment period

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2022-02-25)
• Statistical Analysis Plan (PDF, 2022-10-07)