Clinical trial NCT04605549: A Study of CIN-107 in Adults With Primary Aldosteronism
Official title: A Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Effectiveness of CIN-107 for the Management of Blood Pressure in Patients With Primary Aldosteronism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Aldosteronism
Hyperaldosteronism
Keywords: Primary Aldosteronism
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-10-28
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the safety and tolerability of CIN-107
timeFrame: 74 Weeks
measure: Change in mean seated systolic blood pressure (SBP)
timeFrame: after 12 weeks of treatment
Secondary outcomes:
measure: Change in mean diastolic blood pressure (DBP)
timeFrame: after 12 weeks of treatment
measure: The percentage of patients achieving a seated blood pressure (BP) response <140/90 mmHg
timeFrame: at Week 12
measure: The percentage of patients achieving a seated BP response <130/80 mmHg
timeFrame: at Week 12
measure: The percentage of patients 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
timeFrame: after 12 weeks of treatment
Other outcomes:
Locations:
city: Greenbrae
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: West Hollywood
country: United States
facility: Research Site
state: California
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Dallas
country: United States
facility: Research Site
state: Texas
Study officials:
References: