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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 15
- 试验地点
- 10
- 主要终点
- Number of Treatment Emergent Adverse Events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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/m
- •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 m
- •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.
研究组 & 干预措施
CIN-107 for dosing at 2, 4, or 8 mg (QD)
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.
干预措施: CIN-107 2 mg dosing (Drug)
CIN-107 for dosing at 2, 4, or 8 mg (QD)
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.
干预措施: CIN-107 4 mg dosing (Drug)
CIN-107 for dosing at 2, 4, or 8 mg (QD)
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.
干预措施: CIN-107 8 mg dosing (Drug)
结局指标
主要结局
Number of Treatment Emergent Adverse Events
时间窗: 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
时间窗: 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.
次要结局
- Change From Baseline in Mean Diastolic Blood Pressure (DBP) in Patients With Primary Aldosteronism(12 weeks)
- The Percentage of Patients Achieving a Seated BP Response of <140/90 mmHg(12 weeks)
- The Percentage of Patients Achieving a Seated BP Response of <130/80 mmHg(12 weeks)
- The Percentage of Patients Achieving the Pharmacodynamic Marker Response(12 weeks)