Open-Label Extension Study of Patients Previously Enrolled in Study CIN-107-124

Phase 2

Completed

Conditions: Hypertension

Interventions: Drug: CIN-107

Registration Number: NCT05459688

Lead Sponsor: AstraZeneca

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 175

Inclusion Criteria

Have completed Part 1 or Part 2 of Study CIN-107-124;
Have had acceptable safety and tolerability during Study CIN-107-124 as determined by the Investigator or Medical Monitor;
Have demonstrated ≥70% and ≤120% adherence to their single background antihypertensive agent and the CIN-107 placebo during Study CIN-107-124;
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.
Are able and willing to give informed consent for participation in the clinical study.

Exclusion Criteria

Have met Protocol-defined stopping criteria, were withdrawn from the study, discontinued CIN-107 at the time of Visits 6 or 9, or were not compliant with the Protocol during Study CIN-107-124;
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;
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;
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;
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;
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;
Have experienced a de novo or reactivated serious viral infection such as hepatitis B, hepatitis C, or HIV during Study CIN-107-124;
Have had any major episode of infection requiring hospitalization or treatment with intravenous antibiotics during Study CIN-107-124;
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;
Have anticipated initiation of erythropoietin-stimulating agents and/or planned transfusion within 2 months after enrollment (Visit 1);
Are expected to receive or are receiving any of the exclusionary drugs (strong cytochrome P450 3A inducers);
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;
Have been diagnosed with New York Heart Association stage III or IV chronic heart failure during Study CIN-107-124;
Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure during Study CIN-107-124;
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;
Have a planned coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) or any major surgical procedure;
Have had a CABG or other major cardiac surgery (eg, valve replacement), peripheral arterial bypass surgery, or PCI during Study CIN-107-124;
Have a planned dialysis or kidney transplant during the course of this study;
Have a known hypersensitivity to CIN-107 or drugs of the same class, or any of its excipients;
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;
Are pregnant, breastfeeding, or planning to become pregnant during the study; or
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental 2 mg CIN-107 tablets QD	CIN-107	Treatment with 2 mg CIN-107 tablets, by mouth, once per day. Starting at Visit 1 and concluding at EOT (Visit 7).

Primary Outcome Measures

Name	Time	Method
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)	52 weeks	An AE was defined as any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and/or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational medicinal product, whether or not related to the investigational medicinal product. Any medical condition already present at enrollment should be recorded as medical history and not be reported as an AE unless the medical condition or signs or symptoms present at baseline changes in severity, frequency, or seriousness at any time during the study. In this case, it was be reported as an AE.
Number of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESIs)	52 weeks	For this study, AESIs include the following: Events of hypotension that require clinical intervention; Abnormal potassium laboratory values that require clinical intervention; and Abnormal sodium laboratory values that require clinical intervention.
Change From Baseline in Seated Heart Rate	52 weeks	Change from baseline at 52 weeks in seated heart rate (beats/min)
Number of Participants With Any Treatment-emergent Serious Adverse Events (TESAEs)	52 weeks	An AE was or adverse reaction is considered serious if, in the view of either the Investigator or Sponsor, it results in any of the following outcomes: Death, a life-threatening AE, a persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event.
Change From Baseline in Serum Potassium	52 weeks	Mean change from baseline at Week 52 in serum potassium (mmol/L).
Change From Baseline in Serum Sodium	52 weeks	Mean change from baseline at Week 52 in serum sodium (mmol/L).
Change From Baseline in Body Weight	52 weeks	Change from baseline at 52 weeks in body weight (kg)
Change From Baseline in Temperature	52 weeks	Change from baseline at 52 weeks in temperature (C)

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Seated Systolic Blood Pressure	52 weeks	Mean change from baseline at Week 52 in seated systolic blood pressure (SBP)
Change From Baseline in Mean Seated Diastolic Blood Pressure	52 weeks	Mean change from baseline at 52 weeks in mean seated diastolic blood pressure (DBP)
Achieving Mean Seated Systolic Blood Pressure <130 mmHg	52 weeks	Number of participants achieved mean seated systolic blood pressure (SBP) \<130 mmHg at 52 week
Non-responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg	52 weeks	Number of non-responders (participants with seated SBP \>=130 mmHg) in Study CIN-107-124 achieving a seated SBP response \<130 mmHg with CIN-107 with/without a single background antihypertensive agent and/or rescue medication and irrespective of Study CIN-107-124 dose strength.
Responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg	52 weeks	Number of responders (participants with \<130 mmHg) in Study CIN-107-124 achieving a seated SBP response \<130 mmHg with CIN-107 with/without a single background antihypertensive agent and/or rescue medication and irrespective of Study CIN-107-124 dose strength.