Hyperaldosteronism, Primary Aldosteronism
Conditions
Keywords
Primary Aldosteronism
Brief summary
This is a multicenter, open-label study in adult patients with PA to evaluate the effectiveness and safety of CIN-107 after up to 12 weeks of treatment (Part 1), and then for eligible, consenting patients follow patients in Part 2 for up to 74 weeks for evidence of long-term safety and tolerability.
Detailed description
For patients in Part 1 only : The treatment duration for patients who complete all 3 dose levels, and who opt not to continue in the extension part of the study, is 12 weeks. For patients who do not complete up-titration, the treatment duration will include at least 4 weeks of dosing with the final dose level. If down-titration of CIN-107 dose is determined at Visit 6 (Week 9), the total treatment duration may be extended to 13 weeks to allow sufficient time for CIN-107 treatment effect at the final dose to be assessed. If the final dose of CIN-107 is reached before week 8 (Visit 5) and no up-titration occurs at Visit 5, the patients will be encouraged to continue CIN-107 treatment till Visit 7 for a total of 12 weeks of treatment. The patients who opt not to continue to Part 2 will not receive any study drug and will return for their safety follow up visit (Visit 8) in 2 weeks. For patients who opt to continue in the extension part (Part 2) of the study: Patients will continue to receive their dose of baxdrostat and be instructed to measure BP at least once every week prior to dosing with CIN-107 in the morning, during the extension phase. Safety surveillance will be conducted if clinically indicated. Repeat and unscheduled testing for serum potassium may be measured at the investigator's clinical site or at local laboratory for a faster turn-around time to allow clinical assessment. These patients entering part 2 will skip Visit 8 and their next visit will be Visit 9.
Interventions
DRUGCIN-107 2 mg dosing
One tablet of CIN-107 2 mg tablets, once daily, by mouth, for dosing at 2 mg.
DRUGCIN-107 4 mg dosing
Two tablets of CIN-107 2 mg tablets, once daily, by mouth, for dosing at 4 mg.
DRUGCIN-107 8 mg dosing
Four tablets of CIN-107 2 mg tablets, once daily, by mouth, for dosing at 8 mg.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Have been diagnosed with PA. 2. Are taking mineralocorticoid receptor antagonist (MRA) to control BP; or are newly diagnosed with PA and have not started MRA treatment. 3. Are willing and able to cease dosing of MRA for up to 4 weeks in patients taking MRA. 4. Are willing to be compliant with the contraception and reproduction restrictions of the study. 5. Have increased SBP by ≥ 20 mmHg or have SBP ≥ 160 mmHg after dosing of MRA treatment is ceased for up to 4 weeks duration, or have SBP ≥ 150 mmHg for patients who are newly diagnosed with PA and have not taken an MRA in the past 12 weeks.
Exclusion criteria
1. At Screening Visit, have a single occurrence of mean seated SBP \> 180 mmHg or DBP \> 110 mmHg if not taking an MRA; or have a mean seated SBP ≥ 160 mmHg or DBP ≥ 100 mmHg if currently taking an MRA. 2. Have a body mass index \> 45 kg/m2. 3. Have had a previous surgical intervention for an adrenal adenoma or have a planned adrenal carcinoma, adrenalectomy, renal nerve denervation, or adrenal ablative procedure during the course of the study. 4. Have a documented estimated glomerular filtration rate \< 45 mL/min/1.73 m2. 5. Have a planned dialysis, kidney transplantation or any major surgical procedure during the course of the study. 6. Have known documented New York Heart Association class III or IV chronic heart failure. 7. Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure within 6 months before the Screening Visit. 8. Have known current severe left ventricular outflow obstruction. 9. Have had major cardiac surgery within 6 months before the Screening Visit. 10. Have a history of, or currently experiencing, clinically significant arrhythmias. 11. Have had a prior solid organ transplant or cell transplant. 12. Are positive for HIV antibody, hepatitis C virus RNA, or hepatitis B surface antigen. 13. Have typical consumption of \> 14 alcoholic drinks weekly.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Emergent Adverse Events | 74 weeks | An AE is defined as any untoward medical occurrence in a clinical investigation that occurs to a patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Adverse events were collected from the beginning of the study until Week 74. Treatment emergent AEs are defined as AEs that newly occur or worsen in severity during the treatment period. |
| Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) in Patients With Primary Aldosteronism | 12 weeks | The mean seated SBP was defined as the average of 3 measurements obtained at the clinical site visit. The change from baseline in mean seated SBP after 12 weeks of treatment with CIN-107 (Part 1) is calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Diastolic Blood Pressure (DBP) in Patients With Primary Aldosteronism | 12 weeks | The mean DBP was defined as the average of 3 measurements obtained at the clinical site visit. The change from baseline in mean DBP after 12 weeks of treatment with CIN-107 (Part 1) is calculated. |
| The Percentage of Patients Achieving a Seated BP Response of <140/90 mmHg | 12 weeks | The percentage of patients achieving a mean seated SBP \<140 mmHg and a mean DBP of \<90 mmHg after 12 weeks of treatment with CIN-107 (Part 1) is calculated. |
| The Percentage of Patients Achieving a Seated BP Response of <130/80 mmHg | 12 weeks | The percentage of patients achieving a mean seated SBP \<130 mmHg and a mean DBP of \<80 mmHg after 12 weeks of treatment with CIN-107 (Part 1) is calculated. |
| The Percentage of Patients Achieving the Pharmacodynamic Marker Response | 12 weeks | Pharmacodynamic marker response is defined as achieving either: - a plasma aldosterone concentration (PAC) \< 15 ng/dL and a plasma renin activity (PRA) ≥ 0.5 ng/mL/h; or - an ARR \< 15; or - unsuppressed renin activity PRA ≥ 1.0 ng/mL/h |
Countries
United States
Participant flow
Recruitment details
The study was conducted from 08 March 2021 to 28 October 2024 at 10 sites in United States
Pre-assignment details
A total of 33 subjects were screened (signed consent), 15 subjects have been randomized into the study. 15 subjects completed Part 1 of the study and 14 subjects entered Part 2 of the study, 2 of those withdrew, therefore 12 subjects completed Part 2 of the study
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 53.6 Years STANDARD_DEVIATION 11.6 |
| Race/Ethnicity, Customized ASIAN | 3 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 4 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized WHITE | 7 Participants |
| Region of Enrollment USA | 15 Participants |
| Seated SBP | 151.5 mmHg STANDARD_DEVIATION 13.46 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 3 | 0 / 13 | 0 / 8 | 0 / 4 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 11 / 15 | 1 / 3 | 8 / 13 | 2 / 8 | 4 / 4 | 6 / 7 | 7 / 7 |
| serious Total, serious adverse events | 0 / 15 | 0 / 3 | 0 / 13 | 0 / 8 | 0 / 4 | 0 / 7 | 1 / 7 |
Outcome results
None listed