Back to resultsA Study of CIN-107 in Adults With Primary Aldosteronism
Primary Purpose
Primary Aldosteronism, Hyperaldosteronism
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CIN-107 2 mg dosing
CIN-107 4 mg dosing
CIN-107 8 mg dosing
Sponsored by
About this trial
This is an interventional treatment trial for Primary Aldosteronism focused on measuring Primary Aldosteronism
Eligibility Criteria
Inclusion Criteria:
- Have been diagnosed with PA.
- Are taking mineralocorticoid receptor antagonist (MRA) to control BP; or are newly diagnosed with PA and have not started MRA treatment.
- Are willing and able to cease dosing of MRA for up to 4 weeks in patients taking MRA.
- Are willing to be compliant with the contraception and reproduction restrictions of the study.
- 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:
- 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.
- Have a body mass index > 45 kg/m2.
- 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.
- Have a documented estimated glomerular filtration rate < 45 mL/min/1.73 m2.
- Have a planned dialysis, kidney transplantation or any major surgical procedure during the course of the study.
- Have known documented New York Heart Association class III or IV chronic heart failure.
- Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure within 6 months before the Screening Visit.
- Have known current severe left ventricular outflow obstruction.
- Have had major cardiac surgery within 6 months before the Screening Visit.
- Have a history of, or currently experiencing, clinically significant arrhythmias.
- Have had a prior solid organ transplant or cell transplant.
- Are positive for HIV antibody, hepatitis C virus RNA, or hepatitis B surface antigen.
- Have typical consumption of > 14 alcoholic drinks weekly.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CIN-107 for dosing at 2, 4, or 8 mg (QD)
Arm Description
Patients will be provided with an initial dose of CIN-107 and start once daily (QD) dosing of CIN-107 tablets at 2 mg. At Visit 4, CIN-107 dose may be up-titrated to 4 mg QD if the patient has tolerated dosing of CIN-107 at 2 mg and the blood pressure (BP) records indicate minimal hypotension risk. At Visit 5, CIN-107 dose may be up-titrated to 8 mg QD if the patient has tolerated dosing of CIN-107 at 4 mg.
Outcomes
Primary Outcome Measures
To evaluate the safety and tolerability of CIN-107
Outcome measure is overall safety with is a composite of the following individual parameters (unit of measure in brackets):
Adverse Events [number of events];
ECGs [PR interval (msec), RR interval (msec), or QTcF interval (msec); clinically significant ECG findings that are detected during the study will be reported as adverse events];
Clinical laboratory evaluations including standard safety chemistry panel, hematology, coagulation, and urinalysis [clinically significant abnormal laboratory findings that are detected during the study will be reported as adverse events];
Vital signs [pulse, temperature, heart rate and blood pressure] and physical examination data changes noted as clinically significant abnormalities that arise during the study will be recorded as adverse events
Change in mean seated systolic blood pressure (SBP)
Effectiveness measured by change in mean seated SBP after 12 weeks of treatment in patients with PA
Secondary Outcome Measures
Change in mean diastolic blood pressure (DBP)
Comparison of changes in mean SBP after 12 weeks of treatment in patients with PA.
The percentage of patients achieving a seated blood pressure (BP) response <140/90 mmHg
The percent of patients who achieved a seated BP response <140/90 mmHg after CIN107 treatment will be evaluated at each dose level at Week 12.
The percentage of patients achieving a seated BP response <130/80 mmHg
The percent of patients who achieved a seated BP response <130/80 mmHg after CIN107 treatment will be evaluated at each dose level at Week 12.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04605549
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 8, 2021 (Actual)
Primary Completion Date
October 10, 2024 (Anticipated)
Study Completion Date
October 10, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Aldosteronism, Hyperaldosteronism
Keywords
Primary Aldosteronism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CIN-107 for dosing at 2, 4, or 8 mg (QD)
Arm Type
Experimental
Arm Description
Patients will be provided with an initial dose of CIN-107 and start once daily (QD) dosing of CIN-107 tablets at 2 mg. At Visit 4, CIN-107 dose may be up-titrated to 4 mg QD if the patient has tolerated dosing of CIN-107 at 2 mg and the blood pressure (BP) records indicate minimal hypotension risk.
At Visit 5, CIN-107 dose may be up-titrated to 8 mg QD if the patient has tolerated dosing of CIN-107 at 4 mg.
Intervention Type
Drug
Intervention Name(s)
CIN-107 2 mg dosing
Intervention Description
One tablet of CIN-107 2 mg tablets, once daily, by mouth, for dosing at 2 mg.
Intervention Type
Drug
Intervention Name(s)
CIN-107 4 mg dosing
Intervention Description
Two tablets of CIN-107 2 mg tablets, once daily, by mouth, for dosing at 4 mg.
Intervention Type
Drug
Intervention Name(s)
CIN-107 8 mg dosing
Intervention Description
Four tablets of CIN-107 2 mg tablets, once daily, by mouth, for dosing at 8 mg.
Primary Outcome Measure Information:
Title
To evaluate the safety and tolerability of CIN-107
Description
Outcome measure is overall safety with is a composite of the following individual parameters (unit of measure in brackets):
Adverse Events [number of events];
ECGs [PR interval (msec), RR interval (msec), or QTcF interval (msec); clinically significant ECG findings that are detected during the study will be reported as adverse events];
Clinical laboratory evaluations including standard safety chemistry panel, hematology, coagulation, and urinalysis [clinically significant abnormal laboratory findings that are detected during the study will be reported as adverse events];
Vital signs [pulse, temperature, heart rate and blood pressure] and physical examination data changes noted as clinically significant abnormalities that arise during the study will be recorded as adverse events
Time Frame
74 Weeks
Title
Change in mean seated systolic blood pressure (SBP)
Description
Effectiveness measured by change in mean seated SBP after 12 weeks of treatment in patients with PA
Time Frame
after 12 weeks of treatment
Secondary Outcome Measure Information:
Title
Change in mean diastolic blood pressure (DBP)
Description
Comparison of changes in mean SBP after 12 weeks of treatment in patients with PA.
Time Frame
after 12 weeks of treatment
Title
The percentage of patients achieving a seated blood pressure (BP) response <140/90 mmHg
Description
The percent of patients who achieved a seated BP response <140/90 mmHg after CIN107 treatment will be evaluated at each dose level at Week 12.
Time Frame
at Week 12
Title
The percentage of patients achieving a seated BP response <130/80 mmHg
Description
The percent of patients who achieved a seated BP response <130/80 mmHg after CIN107 treatment will be evaluated at each dose level at Week 12.
Time Frame
at Week 12
Title
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
Time Frame
after 12 weeks of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have been diagnosed with PA.
Are taking mineralocorticoid receptor antagonist (MRA) to control BP; or are newly diagnosed with PA and have not started MRA treatment.
Are willing and able to cease dosing of MRA for up to 4 weeks in patients taking MRA.
Are willing to be compliant with the contraception and reproduction restrictions of the study.
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:
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.
Have a body mass index > 45 kg/m2.
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.
Have a documented estimated glomerular filtration rate < 45 mL/min/1.73 m2.
Have a planned dialysis, kidney transplantation or any major surgical procedure during the course of the study.
Have known documented New York Heart Association class III or IV chronic heart failure.
Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure within 6 months before the Screening Visit.
Have known current severe left ventricular outflow obstruction.
Have had major cardiac surgery within 6 months before the Screening Visit.
Have a history of, or currently experiencing, clinically significant arrhythmias.
Have had a prior solid organ transplant or cell transplant.
Are positive for HIV antibody, hepatitis C virus RNA, or hepatitis B surface antigen.
Have typical consumption of > 14 alcoholic drinks weekly.
Facility Information:
Facility Name
Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Research Site
City
West Hollywood
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Research Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9047
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
IPD Sharing URL
https://vivli.org/
Learn more about this trial
A Study of CIN-107 in Adults With Primary Aldosteronism
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