Resistant Hypertension
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, dose-ranging Phase 2 study to evaluate the efficacy and safety of CIN-107 as compared to placebo after 12 weeks of treatment in patients with treatment-resistant hypertension (rHTN).
Interventions
DRUGCIN-107
CIN-107 tablets by mouth once daily
DRUGPlacebo
placebo tablets by mouth once daily
Sponsors
CinCor Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is on a stable regimen of ≥ 3 antihypertensive agents (one of which is a diuretic) for at least 4 weeks prior to randomization; * Be at least 70% compliant to their anti-hypertensive medication regimen; * Has a seated BP ≥ 130/80 mmHg; * Agrees to comply with the contraception and reproduction restrictions of the study; and * Able to understand and willing to comply with all study visits, procedures, restrictions, and provide written informed consent according to institutional and regulatory guidelines.
Exclusion criteria
* Has a seated SBP ≥ 180 mmHg or DBP ≥ 110 mmHg; * Has a body mass index (BMI) \> 40 kg/m2; * Has an upper arm circumference \< 7 or \> 17 inches; * Has been on night shifts at any time during the 4 weeks before Screening; * Is using a beta blocker for any primary indication other than systemic hypertension (eg, migraine headache); * Is not willing or not able to discontinue an MRA or a potassium sparing diuretic as part of an existing antihypertensive regimen; * Is not willing or not able to discontinue taking a potassium supplement; * Has documented estimated glomerular filtration rate (eGFR) \< 45 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; * Has known current severe left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease diagnosed from a prior echocardiogram; * Major cardiac surgery (eg, CABG, valve replacement), peripheral arterial bypass surgery, or PCI within 6 months before Screening; * Has chronic permanent atrial fibrillation; * Has uncontrolled diabetes with glycosylated hemoglobin \> 9.5% at Screening; * Has planned dialysis or kidney transplant during the course of this study; * Potassium \< 3.5 mEq/L; * Potassium \> 5.0 mEq/L; * Is positive for HIV antibody, hepatitis C virus RNA, or hepatitis B surface antigen; * Has typical consumption of ≥14 alcoholic drinks weekly.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Mean Seated Systolic BP (SBP) | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Mean Seated Diastolic BP (DBP) | 12 weeks |
| The Percentage of Patients Achieving a Seated BP Response <130/80 mmHg | 12 weeks |
Countries
United States
Participant flow
Pre-assignment details
There was a 2-week Single Blind Run-In (SB-RI) period with administration of placebo before inclusion in the double-blind, randomized part of the study. 360 patients entered SB-RI and 85 patients withdrew early from SB-RI. 275 patients were randomized to 1 of the 4 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| CIN-107 Dose 1 (0.5mg) CIN-107: CIN-107 tablets by mouth once daily | 69 |
| CIN-107 Dose 2 (1mg) CIN-107: CIN-107 tablets by mouth once daily | 70 |
| CIN-107 Dose 3 (2mg) CIN-107: CIN-107 tablets by mouth once daily | 67 |
| Placebo Placebo: placebo tablets by mouth once daily | 69 |
| Total | 275 |
Baseline characteristics
| Characteristic | CIN-107 Dose 1 (0.5mg) | CIN-107 Dose 2 (1mg) | CIN-107 Dose 3 (2mg) | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 31 Participants | 26 Participants | 37 Participants | 124 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 39 Participants | 41 Participants | 32 Participants | 151 Participants |
| Age, Continuous | 61.5 Years STANDARD_DEVIATION 10.28 | 62.7 Years STANDARD_DEVIATION 10.14 | 61.2 Years STANDARD_DEVIATION 10.77 | 63.8 Years STANDARD_DEVIATION 10.78 | 62.3 Years STANDARD_DEVIATION 10.48 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 20 Participants | 19 Participants | 16 Participants | 77 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 48 Participants | 47 Participants | 51 Participants | 191 Participants |
| Region of Enrollment United States | 69 participants | 70 participants | 67 participants | 69 participants | 275 participants |
| Seated SBP | 147.6 mmHg STANDARD_DEVIATION 12.49 | 147.7 mmHg STANDARD_DEVIATION 13.05 | 147.3 mmHg STANDARD_DEVIATION 11.82 | 148.9 mmHg STANDARD_DEVIATION 12.38 | 147.9 mmHg STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 33 Participants | 33 Participants | 29 Participants | 27 Participants | 122 Participants |
| Sex: Female, Male Male | 36 Participants | 37 Participants | 38 Participants | 42 Participants | 153 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 69 | 0 / 67 | 0 / 69 |
| other Total, other adverse events | 6 / 69 | 16 / 69 | 8 / 67 | 10 / 69 |
| serious Total, serious adverse events | 0 / 69 | 2 / 69 | 6 / 67 | 2 / 69 |
Outcome results
Primary
Change From Baseline in Mean Seated Systolic BP (SBP)
Time frame: 12 weeks
Population: Only patients with non-missing baseline and the specified visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| mITT Population 0.5mg | Change From Baseline in Mean Seated Systolic BP (SBP) | -12.4 mmHg | Standard Deviation 15.63 |
| mITT Population 1mg | Change From Baseline in Mean Seated Systolic BP (SBP) | -17.3 mmHg | Standard Deviation 18.1 |
| mITT Population 2mg | Change From Baseline in Mean Seated Systolic BP (SBP) | -19.2 mmHg | Standard Deviation 15.84 |
| mITT Population Placebo | Change From Baseline in Mean Seated Systolic BP (SBP) | -9.8 mmHg | Standard Deviation 13.71 |
Secondary
Change From Baseline in Mean Seated Diastolic BP (DBP)
Time frame: 12 weeks
Population: Only patients with non-missing baseline and the specified visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| mITT Population 0.5mg | Change From Baseline in Mean Seated Diastolic BP (DBP) | -9.1 mmHg | Standard Deviation 9.04 |
| mITT Population 1mg | Change From Baseline in Mean Seated Diastolic BP (DBP) | -11.7 mmHg | Standard Deviation 9.88 |
| mITT Population 2mg | Change From Baseline in Mean Seated Diastolic BP (DBP) | -14.0 mmHg | Standard Deviation 12.42 |
| mITT Population Placebo | Change From Baseline in Mean Seated Diastolic BP (DBP) | -9.3 mmHg | Standard Deviation 9.6 |
Secondary
The Percentage of Patients Achieving a Seated BP Response <130/80 mmHg
Time frame: 12 weeks
Population: The modified ITT (mITT) Population included all patients in the ITT Population who received at least 1 dose of any study drug and had a baseline value for the SBP assessment. Any efficacy measurement obtained after a patient received a restricted BP altering therapy, outside of the current study design, was removed from the mITT analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| mITT Population 0.5mg | The Percentage of Patients Achieving a Seated BP Response <130/80 mmHg | 21 Participants |
| mITT Population 1mg | The Percentage of Patients Achieving a Seated BP Response <130/80 mmHg | 28 Participants |
| mITT Population 2mg | The Percentage of Patients Achieving a Seated BP Response <130/80 mmHg | 26 Participants |
| mITT Population Placebo | The Percentage of Patients Achieving a Seated BP Response <130/80 mmHg | 21 Participants |