Chronic Kidney Diseases, Uncontrolled Hypertension
Conditions
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.
Interventions
DRUGCIN-107
Patients will take CIN-107 tablets by mouth once daily.
DRUGPlacebo
Patients will take placebo tablets by mouth once daily.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
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\^2. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) of Pooled CIN-107 and Placebo | At Week 26 | Mean change in seated SBP from baseline to Week 26 of pooled CIN-107 and placebo was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in SBP in CIN-107 Compared to Placebo in Participants Assigned to the High-dose Strategy Group | At Week 26 | Mean change in seated SBP from baseline to Week 26 of high-dose CIN-107 dosing group and placebo was assessed. |
| Change From Baseline of SBP in CIN-107 Compared to Placebo in Participants Assigned to the Low-dose Strategy Group | At Week 26 | The mean change in seated SBP from baseline to Week 26 of low-dose CIN-107 dosing group and placebo was assessed. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From randomization (Day 1) until the end of Follow up period (approximately 8 months) | The safety and tolerability of CIN-107 in participants with uncontrolled hypertension (uHTN) and chronic kidney disease (CKD) was assessed. Adverse events of special interest (AESI) include any hypotension events, abnormal potassium or sodium laboratory values that require clinical intervention. |
Countries
United States
Participant flow
Recruitment details
This study was conducted from 29 April 2022 to 02 May 2024 at 78 sites in the United States.
Pre-assignment details
Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| CIN-107 Low Dosing Strategy Group Participants received oral tablets of low dose strengths of CIN-107 for 26 weeks. | 65 |
| CIN-107 High Dosing Strategy Group Participants received oral tablets of high dose strengths of CIN-107 for 26 weeks. | 64 |
| Placebo Participants received oral tablets of Placebo for 26 weeks. | 66 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 1 |
| Overall Study | Inclusion/exclusion criteria not met | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 3 | 2 |
| Overall Study | Other | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 4 | 11 |
Baseline characteristics
| Characteristic | CIN-107 Low Dosing Strategy Group | CIN-107 High Dosing Strategy Group | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous Age | 67.2 Years STANDARD_DEVIATION 12.63 | 66.5 Years STANDARD_DEVIATION 11.02 | 65.6 Years STANDARD_DEVIATION 10.79 | 66.4 Years STANDARD_DEVIATION 11.46 |
| Race/Ethnicity, Customized Race Asian | 4 Participants | 3 Participants | 5 Participants | 12 Participants |
| Race/Ethnicity, Customized Race Black or African American | 19 Participants | 24 Participants | 20 Participants | 63 Participants |
| Race/Ethnicity, Customized Race Not Reported | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Race White | 41 Participants | 34 Participants | 38 Participants | 113 Participants |
| Sex: Female, Male Female | 23 Participants | 21 Participants | 19 Participants | 63 Participants |
| Sex: Female, Male Male | 42 Participants | 43 Participants | 47 Participants | 132 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 63 | 0 / 64 |
| other Total, other adverse events | 47 / 65 | 52 / 63 | 35 / 64 |
| serious Total, serious adverse events | 7 / 65 | 5 / 63 | 2 / 64 |
Outcome results
Primary
Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) of Pooled CIN-107 and Placebo
Mean change in seated SBP from baseline to Week 26 of pooled CIN-107 and placebo was assessed.
Time frame: At Week 26
Population: Modified Intent-to-treat (mITT) population included all participants in the ITT population who received at least 1 dose of any study drug.~Here, 'overall number of participants analyzed' means the number of participants with non-missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CIN-107 Treatment Groups Pooled | Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) of Pooled CIN-107 and Placebo | -15.22 Millimeters of mercury (mmHg) | Standard Error 1.532 |
| Placebo | Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) of Pooled CIN-107 and Placebo | -7.15 Millimeters of mercury (mmHg) | Standard Error 2.231 |
Comparison: The analysis was performed using a mixed-effect model for repeated measures including fixed effects for treatment, visit, stratification variables (SGLT2 inhibitor use and CKD category), and the treatment-by-visit interaction, along with a covariate of the baseline seated SBP value and the baseline seated SBP by visit interaction.p-value: 0.00395% CI: [-13.36, -2.79]Mixed Models Analysis
Secondary
Change From Baseline in SBP in CIN-107 Compared to Placebo in Participants Assigned to the High-dose Strategy Group
Mean change in seated SBP from baseline to Week 26 of high-dose CIN-107 dosing group and placebo was assessed.
Time frame: At Week 26
Population: mITT population included all participants in the ITT population who received at least 1 dose of any study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CIN-107 Treatment Groups Pooled | Change From Baseline in SBP in CIN-107 Compared to Placebo in Participants Assigned to the High-dose Strategy Group | -14.37 mmHg | Standard Error 2.117 |
| Placebo | Change From Baseline in SBP in CIN-107 Compared to Placebo in Participants Assigned to the High-dose Strategy Group | -7.16 mmHg | Standard Error 2.233 |
Comparison: The analysis was performed using a mixed-effect model for repeated measures including fixed effects for treatment, visit, stratification variables (SGLT2 inhibitor use and CKD category), and the treatment-by-visit interaction, along with a covariate of the baseline seated SBP value and the baseline seated SBP by visit interaction.p-value: 0.01995% CI: [-13.24, -1.19]Mixed Models Analysis
Secondary
Change From Baseline of SBP in CIN-107 Compared to Placebo in Participants Assigned to the Low-dose Strategy Group
The mean change in seated SBP from baseline to Week 26 of low-dose CIN-107 dosing group and placebo was assessed.
Time frame: At Week 26
Population: mITT population included all participants in the ITT population who received at least 1 dose of any study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CIN-107 Treatment Groups Pooled | Change From Baseline of SBP in CIN-107 Compared to Placebo in Participants Assigned to the Low-dose Strategy Group | -16.14 mmHg | Standard Error 2.186 |
| Placebo | Change From Baseline of SBP in CIN-107 Compared to Placebo in Participants Assigned to the Low-dose Strategy Group | -7.16 mmHg | Standard Error 2.233 |
Comparison: The analysis was performed using a mixed-effect model for repeated measures including fixed effects for treatment, visit, stratification variables (SGLT2 inhibitor use and CKD category), and the treatment-by-visit interaction, along with a covariate of the baseline seated SBP value and the baseline seated SBP by visit interaction.p-value: 0.00495% CI: [-15.1, -2.87]Mixed Models Analysis
Other Pre-specified
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
The safety and tolerability of CIN-107 in participants with uncontrolled hypertension (uHTN) and chronic kidney disease (CKD) was assessed. Adverse events of special interest (AESI) include any hypotension events, abnormal potassium or sodium laboratory values that require clinical intervention.
Time frame: From randomization (Day 1) until the end of Follow up period (approximately 8 months)
Population: Safety population included all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of treatment, related to treatment | 7 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of study, related to treatment | 0 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TESAEs, related to treatment | 2 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE with outcome = Death | 0 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE with outcome = Death, related to treatment | 0 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of treatment, related to treatment | 2 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of study | 0 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of study, related to treatment | 0 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment emergent AESIs | 11 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE with outcome = Death | 0 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to dose interruption | 20 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TEAEs | 48 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TEAEs, related to treatment | 23 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE with outcome = Death, related to treatment | 0 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to dose interruption, related to treatment | 10 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of treatment | 10 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of study | 0 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All treatment emergent serious adverse events (TESAEs) | 7 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to dose interruption | 2 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to dose interruption, related to treatment | 0 Participants |
| CIN-107 Treatment Groups Pooled | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of treatment | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TEAEs | 52 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of study | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of study | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to dose interruption, related to treatment | 10 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of study, related to treatment | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment emergent AESIs | 12 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TEAEs, related to treatment | 31 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TESAEs, related to treatment | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to dose interruption, related to treatment | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE with outcome = Death | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All treatment emergent serious adverse events (TESAEs) | 5 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of treatment | 11 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE with outcome = Death, related to treatment | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE with outcome = Death | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to dose interruption | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to dose interruption | 23 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of treatment | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of treatment, related to treatment | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE with outcome = Death, related to treatment | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of study, related to treatment | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of treatment, related to treatment | 8 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of study | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of study, related to treatment | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of treatment, related to treatment | 3 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment emergent AESIs | 4 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE with outcome = Death, related to treatment | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All treatment emergent serious adverse events (TESAEs) | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TEAEs | 35 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TESAEs, related to treatment | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All TEAEs, related to treatment | 14 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE with outcome = Death | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to dose interruption | 13 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of treatment | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of study | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of study, related to treatment | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to dose interruption, related to treatment | 4 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE with outcome = Death | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE with outcome = Death, related to treatment | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to dose interruption | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of treatment | 5 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to discontinuation of treatment, related to treatment | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TESAE leading to dose interruption, related to treatment | 1 Participants |