A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group, Dose-Ranging Study to Evaluate CIN-107 for the Treatment of Patients With Uncontrolled Hypertension and Chronic Kidney Disease
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 195
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) of Pooled CIN-107 and Placebo
Study Overview
Brief Summary
This study will evaluate the efficacy and safety of CIN-107 for the treatment of hypertension in patients with uncontrolled hypertension (uHTN) and Chronic Kidney Disease (CKD).
Detailed Description
This randomized, double-blind, placebo-controlled will evaluate the efficacy and safety of CIN-107 in patients with uHTN and CKD. Approximately 200 patients will be randomized in a 1:1:1 ratio into 1 of the 3 treatment groups (placebo, low dose treatment strategy and high dose treatment strategy).
The study will consist of the following 3 periods:
- A Screening Period of up to 5 weeks;
- A Double-Blind Treatment Period of 26 weeks; and
- A Follow-Up Period of 2 weeks.
Patients will complete the study in approximately 8 months.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 130 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Has a mean seated SBP ≥ 140 mmHg.
- •Has a prior diagnosis of mild-to-severe CKD.
- •Has an elevated UACR.
- •Is currently taking an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) at the maximum tolerated daily dose.
Exclusion Criteria
- •Have a documented diagnosis of type 1 diabetes.
- •Are not willing or not able to discontinue a mineralocorticoid receptor antagonist (MRA) or a potassium sparing diuretic as part of an existing antihypertensive regimen.
- •Have a single occurrence of mean seated SBP >180 mmHg or DBP >110 mmHg during the Screening Period.
- •Has a body mass index (BMI) >50 kg/m^
- •Has documented bilateral clinically relevant renal artery stenosis of ≥70%.
- •Has had dialysis for acute kidney injury/acute renal failure within 12 weeks prior to the Screening Period or has a planned dialysis or kidney transplantation during the course of the study.
- •Has known documented chronic heart failure New York Heart Association Class III or Class IV and/or hospitalization for heart failure within 6 months of Screening.
- •Has had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure within 6 months of Screening.
- •Has known current severe left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease.
- •Has planned any major cardiac surgery during the study or had major cardiac surgery within 6 months of Screening.
- •Has had a prior solid organ transplant or cell transplant.
- •Has a known hypersensitivity to CIN-107 or drugs of the same class
- •Has received immunotherapy for treatment of CKD within 6 months of Screening.
- •Has any clinically relevant medical or surgical conditions including unstable conditions and/or conditions requiring regular transfusion or treatment with systemic immunosuppressants, including corticosteroids.
- •Serum potassium <3.5 mEq/L or >5.0 mEq/L
- •Serum sodium <135 mEq/L
- •Serum aspartate aminotransferase or alanine aminotransferase >3 × upper limit of normal (ULN); or Total bilirubin >2 × ULN, unless due to Gilbert's syndrome.
- •GFR is < 25 or > 75 mL/min/1.73 m2
- •Has uncontrolled diabetes with glycosylated hemoglobin >10.5%.
- •Is positive for Human immunodeficiency disease (HIV) antibody, hepatitis B surface antigen, or hepatitis C virus Ribonucleic acid (RNA).
- •Has typical consumption of >14 alcoholic drinks weekly.
Arms & Interventions
High dose CIN-107
Patients will take oral tablets of CIN-107 for 26 weeks. The dose strength may be titrated within 6 weeks.
Intervention: CIN-107 (Drug)
Placebo
Patients will take oral tablets of Placebo for 26 weeks. The dose strength may be titrated within 6 weeks.
Intervention: Placebo (Drug)
Low dose CIN-107
Patients will take oral tablets of CIN-107 for 26 weeks. The dose strength may be titrated within 6 weeks.
Intervention: CIN-107 (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) of Pooled CIN-107 and Placebo
Time Frame: At Week 26
Mean change in seated SBP from baseline to Week 26 of pooled CIN-107 and placebo was assessed.
Secondary Outcomes
- Change From Baseline in SBP in CIN-107 Compared to Placebo in Participants Assigned to the High-dose Strategy Group(At Week 26)
- Change From Baseline of SBP in CIN-107 Compared to Placebo in Participants Assigned to the Low-dose Strategy Group(At Week 26)