NCT02322450已完成2 期
Multicenter, Randomized, Double-blind, Two-period, Placebo Controlled, Forced-titration Proof of Concept Crossover Study to Compare QGC001 With Placebo in Patients With Grade I or II Essential Hypertension
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 4
- 主要终点
- Efficacy - 24h ABPM
研究概览
简要总结
2QG1 is a Phase IIa study aiming to assess the blood pressure lowering effect of 4-week administration of QGC001 oral doses in patients with grade I or II essential hypertension compared to placebo, to assess the safety and tolerability, to obtain preliminary PK information for QGC001 given as multiple oral doses and to determine preliminary PD profile of QGC001 multiple oral doses on plasma and urine hormones, which will be compared to that of placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female of non-childbearing potential patients (post-menopausal since at least 12 months or surgically sterilized) aged 18 to 75 years;
- •Body weight ≥50 kg with a body mass index (BMI) calculated as weight in kg/(height in m2) from 18 to 40 kg/m2 at screening;
- •A signed and dated informed consent form before any study-specific screening procedure is performed;
- •With a diagnosis of essential grade I or II hypertension defined as:
- •a supine office systolic BP (SBP) of 140-159 mmHg or diastolic BP (DBP) of 90-99 mmHg who should have an additional clinical indication according to ESH guidelines for antihypertensive treatment after a 2-week placebo run-in period,
- •or a supine office SBP of 160-179 mmHg or DBP of 100-109 mmHg after a 2-week placebo run-in period with a diagnosis of essential grade II hypertension;
- •Diagnosis of permanent hypertension confirmed by a mean SBP or DBP higher than135 or 85 mmHg on daytime ambulatory blood pressure monitoring (ABPM) after a 2-week placebo run-in period;
- •Estimated glomerular filtration rate (Modification of Diet in Renal Disease (MDRD) formula) ≥ 60 ml/min/1.73 m2.
排除标准
- •Any significant hepatic, renal, respiratory (e.g., asthma), gastrointestinal, endocrine (e.g., diabetes, dyslipidemia necessitating drug therapy), immunologic, dermatological, hematological, neurologic, psychiatric disease or history of any clinically important drug allergy;
- •Acute disease state (e.g., vomiting, fever, diarrhea) within 7 days before study day 1;
- •Any history of transient ischemic accident (TIA) or cerebrovascular accident (CVA);
- •Any history of acute heart failure or heart failure;
- •Any history of myocardial infarction, unstable angina, coronary bypass or percutaneous coronary angioplasty;
- •History of malignant tumor during the past 5 years;
- •Any medical or surgical disorder considered by the investigator as increasing the risks of participation in the study, or liable to prevent the patient from complying with the requirements of the study or from continuing the study to completion;
- •Any situation which, in the investigator's opinion, might compromise assessment of efficacy or of safety;
- •History of non-adherence to treatment;
- •History of drug abuse within 1 year before study day 1;
- •History of alcoholism within 1 year before day 1;
- •Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies;
- •Use of any investigational drug within 30 days before IMP administration;
- •Donation of blood (i.e., 500 ml) within 90 days before study day 1;
- •Known secondary hypertension;
- •Grade III hypertension;
- •Estimated glomerular filtration rate (MDRD formula) below 60 ml/min/1.73 m2 ;
- •Type I diabetes mellitus or uncontrolled type II diabetes mellitus (HbA1C ≥ 8%);
- •Severe obesity (BMI ≥ 40 kg/m2);
- •Arm circumference ≥ 42 cm;
- •Atrial fibrillation;
- •Known hypersensitivity to drugs;
- •History of spontaneous or drug induced angioneurotic edema;
- •Use of any of the following medications within the four (4) weeks prior to dosing:
- •Thyroid medication, statin therapy, oral antidiabetic drugs, estrogen replacement therapy and/or chronic low dose aspirin (75 mg/day) unless the patient has been on a stable maintenance dose for at least 3 months prior to screening.
- •Anticoagulant treatments
- •Cholestyramine resins.
- •Treatment with oral, topical, inhaled, eye drop corticosteroids
- •Treatment with class Ia, Ib and Ic or III anti-arrhythmics
- •CNS drugs
- •P-glycoprotein (P-gp) inhibitors (e.g., verapamil, quinidine, ritonavir),
- •known cytochrome P450 inducers or inhibitors (eg, ketoconazole/CYP3A4, quinidine/CYP2D6, gemfibrozil/CYP2C8)
- •Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDS) or cyclooxygenase (COX)-2 inhibitors.
- •Vasodilators or vascular muscle relaxants prescribed for other conditions
- •Unlikely to cooperate in the study and/or poor compliance anticipated by the investigator, e.g., uncooperative attitude, inability to return for follow-up visit, and unlikelihood of completing the study;
- •Participation in another interventional study at the same time or within 3 months prior to the beginning of the present study;
- •Participant not affiliated with the French social security;
- •No written informed consent;
- •A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms);
- •A history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
- •The use of concomitant medications that prolong the QT/QTc interval.
研究组 & 干预措施
A: P1-QGC001 - Washout-placebo - P2-placebo
Experimental
The first period (P1) will correspond either to QGC001 or placebo, the second period (P2) will correspond either to QGC001 or placebo.
干预措施: QGC001 (Drug)
A: P1-QGC001 - Washout-placebo - P2-placebo
Experimental
The first period (P1) will correspond either to QGC001 or placebo, the second period (P2) will correspond either to QGC001 or placebo.
干预措施: Placebo (Drug)
B: P1-placebo - Washout-placebo - P2-QGC001
Experimental
The first period (P1) will correspond either to QGC001 or placebo, the second period (P2) will correspond either to QGC001 or placebo.
干预措施: QGC001 (Drug)
B: P1-placebo - Washout-placebo - P2-QGC001
Experimental
The first period (P1) will correspond either to QGC001 or placebo, the second period (P2) will correspond either to QGC001 or placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Efficacy - 24h ABPM
时间窗: Change from Period 1 to Period 2 up to 16 weeks (end-of-study visit).
Measurements will include mean 24h systolic and diastolic pressures, and daytime values (measured every 15 min from 07:00 am to 10:00 pm) and night-time values (measured every 20 min from 10:00 pm to 07:00 am). Only ambulatory BP recordings with a minimum of 24 measurements will be considered as successful.
次要结局
- Efficacy - Self BP measurements at home(Change from Period 1 to Period 2 up to 16 weeks.)
- Efficacy - Office BP measurements(Change from Period 1 to Period 2 up to 16 weeks.)
- Efficacy - Hormonal measurements(Change from Period 1 to Period 2 up to 16 weeks.)
- Pharmacokinetics - Plasma levels of QGC001(Change from Period 1 to Period 2 up to 16 weeks.)
- Pharmacokinetics - Plasma levels of EC33(Change from Period 1 to Period 2 up to 16 weeks.)
- Safety - Reported signs and symptoms(Change from Period 1 to Period 2 up to 16 weeks.)
- Safety - Physical examination(Change from Period 1 to Period 2 up to 16 weeks.)
- Safety - Vital sign measurements(Change from Period 1 to Period 2 up to 16 weeks.)
- Safety - Adverse events(Change from Period 1 to Period 2 up to 16 weeks.)
- Safety - Morisky Medication Adherence Questionnaire(Change from Period 1 to Period 2 up to 16 weeks.)
- Safety - Electrocardiogram(Change from Period 1 to Period 2 up to 16 weeks.)
- Safety - Clinical laboratory tests(Change from Period 1 to Period 2 up to 16 weeks.)
研究者
研究点 (4)
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