Clinical trial NCT05459688: Open-Label Extension Study of Patients Previously Enrolled in Study CIN-107-124
Official title: An Open-Label Extension Study of Patients Previously Enrolled in Study CIN-107-124 to Evaluate the Long-Term Safety and Effectiveness of CIN-107
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-07-15
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Eligible patients from Study CIN-107-124 who elect to participate in this study will continue treatment with 2 mg CIN-107 tablets QD after enrollment, starting at Visit 1 and concluding at EOT (Visit 7)
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, multicenter, open-label extension (OLE) study to evaluate the long-term safety, tolerability, and effectiveness of CIN-107 for up to 52 weeks in patients with HTN who have completed Part 1 or Part 2 of Study CIN-107-124. The study will be conducted at clinical sites that have participated in the double-blind, Phase 2 Study CIN-107-124.


Eligibility criteria: Inclusion Criteria:

1. Have completed Part 1 or Part 2 of Study CIN-107-124;
2. Have had acceptable safety and tolerability during Study CIN-107-124 as determined by the Investigator or Medical Monitor;
3. Have demonstrated ≥70% and ≤120% adherence to their single background antihypertensive agent and the CIN-107 placebo during Study CIN-107-124;
4. Agree to comply with the contraception and reproduction restrictions of the study as follows:

   * Male patients must agree to abstain from sperm donation from Day 1 through 90 days after the final dose of study drug;
   * Female patients of childbearing potential (ie, ovulating, pre-menopausal, and not surgically sterile) must have a documented negative serum pregnancy test at enrollment (Visit 1); and
   * Female patients of childbearing potential must use a highly effective method of contraception (ie, \<1% failure rate) from Day 1 through 30 days after the last administration of study drug.
5. Are able and willing to give informed consent for participation in the clinical study.

Exclusion Criteria:

1. Have met Protocol-defined stopping criteria, were withdrawn from the study, discontinued CIN-107 at the time of Visits 6 or 9, or were not compliant with the Protocol during Study CIN-107-124;
2. Have received treatment with any investigational agent for disease intervention (ie, other than study drug) during Study CIN-107-124, or since the last administration of study drug in Study CIN-107-124, or plans to participate in another clinical study within 30 days of discontinuation of study drug;
3. Have had any new, significant, or uncontrolled comorbidity since initially enrolling in Study CIN-107-124 that would increase the risk of the patient in Study CIN-107-130, as determined by the Investigator;
4. Have had a mean seated SBP ≥170 mmHg or DBP ≥105 mmHg at the end of Part 1 or Part 2 of Study CIN-107-124;
5. Have an upper arm circumference that does not meet the cuff measurement criteria for the selected BP machine at Visit 1 of Study CIN-107-130;
6. Have any uncontrolled or clinically significant laboratory abnormality that would affect safety, interpretation of study data, or the patient's participation in the study, as determined by the Investigator;
7. Have experienced a de novo or reactivated serious viral infection such as hepatitis B, hepatitis C, or HIV during Study CIN-107-124;
8. Have had any major episode of infection requiring hospitalization or treatment with intravenous antibiotics during Study CIN-107-124;
9. Have developed a malignancy (with the exception of non-serious local and resectable basal or squamous cell carcinoma of the skin) during Study CIN-107-124;
10. Have anticipated initiation of erythropoietin-stimulating agents and/or planned transfusion within 2 months after enrollment (Visit 1);
11. Are expected to receive or are receiving any of the exclusionary drugs (strong cytochrome P450 3A inducers);
12. Have known secondary causes of HTN (eg, renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, hyperparathyroidism, pheochromocytoma, Cushing's syndrome, or aortic coarctation) except obstructive sleep apnea;
13. Have been diagnosed with New York Heart Association stage III or IV chronic heart failure during Study CIN-107-124;
14. Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure during Study CIN-107-124;
15. Have a known current severe left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease diagnosed from a prior echocardiogram;
16. Have a planned coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass graft \[CABG\]) or any major surgical procedure;
17. Have had a CABG or other major cardiac surgery (eg, valve replacement), peripheral arterial bypass surgery, or PCI during Study CIN-107-124;
18. Have a planned dialysis or kidney transplant during the course of this study;
19. Have a known hypersensitivity to CIN-107 or drugs of the same class, or any of its excipients;
20. Have any clinically relevant medical or surgical conditions (including unstable conditions and/or treatment with systemic immunosuppressants including corticosteroids) that, in the opinion of the Investigator, would put the patient at risk by participating in the study;
21. Are pregnant, breastfeeding, or planning to become pregnant during the study; or
22. Are considered to be unsuitable for any other reason that may either place the patient at increased risk during participation or interfere with the interpretation of the study outcomes by the Investigator, after reviewing medical and psychiatric history, physical examination, and laboratory evaluation.

Primary outcomes:
measure: Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
timeFrame: 52 weeks
measure: Number of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESIs)
timeFrame: 52 weeks
measure: Number of Participants With Any Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: 52 weeks
measure: Change From Baseline in Serum Potassium
timeFrame: 52 weeks
measure: Change From Baseline in Serum Sodium
timeFrame: 52 weeks
measure: Change From Baseline in Body Weight
timeFrame: 52 weeks
measure: Change From Baseline in Temperature
timeFrame: 52 weeks
measure: Change From Baseline in Seated Heart Rate
timeFrame: 52 weeks
Secondary outcomes:
measure: Change From Baseline in Mean Seated Systolic Blood Pressure
timeFrame: 52 weeks
measure: Change From Baseline in Mean Seated Diastolic Blood Pressure
timeFrame: 52 weeks
measure: Achieving Mean Seated Systolic Blood Pressure <130 mmHg
timeFrame: 52 weeks
measure: Non-responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg
timeFrame: 52 weeks
measure: Responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Saraland
country: United States
facility: Research Site
state: Alabama
city: Huntington Park
country: United States
facility: Research Site
state: California
city: Lincoln
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Northridge
country: United States
facility: Research Site
state: California
city: Oceanside
country: United States
facility: Research Site
state: California
city: Panorama City
country: United States
facility: Research Site
state: California
city: Van Nuys
country: United States
facility: Research Site
state: California
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Doral
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Hollywood
country: United States
facility: Research Site
state: Florida
city: Lake Worth
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Winter Haven
country: United States
facility: Research Site
state: Florida
city: Addison
country: United States
facility: Research Site
state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Morton
country: United States
facility: Research Site
state: Illinois
city: Brownsburg
country: United States
facility: Research Site
state: Indiana
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Troy
country: United States
facility: Research Site
state: Michigan
city: Olive Branch
country: United States
facility: Research Site
state: Mississippi
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Edmond
country: United States
facility: Research Site
state: Oklahoma
city: Austin
country: United States
facility: Research Site
state: Texas
city: Carrollton
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Georgetown
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Lampasas
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: West Valley City
country: United States
facility: Research Site
state: Utah
city: Manassas
country: United States
facility: Research Site
state: Virginia
Study officials:
References: