A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Finding Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo After 8 Weeks Treatment in Patients With Essential Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 628
- 试验地点
- 1
- 主要终点
- Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)
研究概览
简要总结
This study was a proof-of-efficacy, dose finding study of LCI699 in participants with mild-to-moderate uncomplicated essential hypertension in order to assess the blood pressure (BP) lowering effect, safety and tolerability of LCI699 as compared to placebo and eplerenone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, 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
- •Males and non-fertile females.
- •18-75 years inclusive.
- •Participants with mild-to-moderate uncomplicated essential hypertension.
排除标准
- •All women of child bearing potential.
- •Female participants on hormone replacement therapy.
- •Severe hypertension.
- •History or evidence of a secondary form of hypertension.
- •Known moderate or malignant retinopathy.
- •History of angina pectoris, myocardial infarction, coronary bypass surgery,ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral vessels), stroke, transient ischemic attack (TIA), carotid artery stenosis, aortic aneurysm or peripheral arterial disease.
- •Type 1 or type 2 diabetes mellitus.
- •Clinically significant valvular heart disease.
- •Congestive heart failure (New York Heart Association [NYHA] class II-IV).
- •Cardiac electrical abnormalities indicating significant risk of safety for participant taking part in the study.
- •History of malignancy of any organ system, treated or untreated, within the past 5 years.
- •Liver disease such as cirrhosis or chronic active hepatitis.
- •Any surgical or medical conditions that may significantly alter the absorption, distribution, metabolism or excretion of any drug substance
- •Any surgical or medical conditions, not identified in the protocol that in the opinion of the investigator or the monitor, place the participant at higher risk from his/her participation in the study, or is likely to prevent the participant from complying with the requirements of the study or completing the trial period.
- •Participant unwilling or not able to discontinue safely the use of current antihypertensive medications during the study period
- •Any contraindication or history of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
- •Chronic oral or parenteral corticosteroid treatment.
- •Treatment with potassium supplement or potassium sparing diuretics.
- •Treatment with potent cytochrome P450 3A4 (CYP3A4) inhibitors during the study period.
- •Use of other investigational drugs at Visit 1, or within 30 days or 5 half-lives of Visit 1, whichever is longer, unless local health authority guidelines mandate a longer period.
- •Serum potassium > 5.2 milliequivalents per liter (mEq/L) or < 3.5 mEq/L at Visit
- •Serum sodium < 132 mEq/L at Visit
- •Aspartate aminotransferase (ALT) or alanine aminotransferase (AST) > 2 times the upper limit of the normal range (ULN) at Visit
- •Bilirubin (total) > 1.5 x ULN at Visit
- •Modification of diet in renal disease estimated glomerular filtration rate (MDRD eGFR) < 60 milliliters per minute (ml/min)/1.73 m^2 at Visit
- •Other clinically significant laboratory abnormalities, confirmed by repeat measurements, at Visit
- •History of active substance abuse (including alcohol).
- •Participants with night-shift employment.
研究组 & 干预措施
Core Period: LCI699 0.25 mg QD
Participants received LCI699 0.25 mg capsules, orally, once daily (QD), with or without food for up to 8 weeks.
干预措施: LCI699 (Drug)
Core Period: LCI699 0.5 mg QD
Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 8 weeks.
干预措施: LCI699 (Drug)
Core Period: LCI699 1.0 mg QD
Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 8 weeks.
干预措施: LCI699 (Drug)
Core Period: LCI699 0.5 mg BID
Participants received LCI699 0.5 mg capsules, orally, twice daily (BID), with or without food for up to 8 weeks.
干预措施: LCI699 (Drug)
Core Period: Eplerenone 50 mg BID
Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 8 weeks.
干预措施: Eplerenone (Drug)
Core Period: Placebo
Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 8 weeks.
干预措施: LCI699-matching Placebo (Drug)
Core Period: Placebo
Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 8 weeks.
干预措施: Eplerenone-matching Placebo (Drug)
Withdrawal Period: LCI699 0.25 mg QD
Participants received LCI699 0.25 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: LCI699 (Drug)
Withdrawal Period: LCI699 0.25 mg QD Placebo
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: LCI699-matching Placebo (Drug)
Withdrawal Period: LCI699 0.5 mg QD
Participants received LCI699 0.5 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: LCI699 (Drug)
Withdrawal Period: LCI699 0.5 mg QD Placebo
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: LCI699-matching Placebo (Drug)
Withdrawal Period: LCI699 1.0 mg QD
Participants received LCI699 1 mg capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: LCI699 (Drug)
Withdrawal Period: LCI699 1.0 mg QD Placebo
Participants received LCI699 matching placebo capsules, orally, QD, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: LCI699-matching Placebo (Drug)
Withdrawal Period: LCI699 0.5 mg BID
Participants received LCI699 0.5 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: LCI699 (Drug)
Withdrawal Period: LCI699 0.5 mg BID Placebo
Participants received LCI699 matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: LCI699-matching Placebo (Drug)
Withdrawal Period: Eplerenone 50 mg BID
Participants received eplerenone 50 mg capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: Eplerenone (Drug)
Withdrawal Period: Eplerenone 50 mg BID Placebo
Participants received eplerenone matching placebo capsules, orally, BID, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: Eplerenone-matching Placebo (Drug)
Withdrawal Period: Placebo
Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: LCI699-matching Placebo (Drug)
Withdrawal Period: Placebo
Participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food for up to 1 week (Week 8 to Week 9).
干预措施: Eplerenone-matching Placebo (Drug)
结局指标
主要结局
Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)
时间窗: Baseline, Week 8
Automated arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV, using an automated BP device (such as the Omron BP monitor). The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSDBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and region as factors and baseline MSDBP level as a covariate.
次要结局
- Core Period: Change From Baseline in Mean 24 Hour Ambulatory DBP at Week 8, as Measured by ABPM(Baseline, Week 8)
- Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP at Week 8(Baseline, every hour up to 24 hours post-dose at Week 8)
- Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP(Baseline, Week 8)
- Core Period: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), and Deaths(AEs: From start of the study drug treatment up to 8 weeks; SAE: From signing of the informed consent up to 8 weeks)
- Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8(Baseline, Week 8)
- Core Period: Change From Baseline in Plasma Aldosterone Levels at Week 8(Baseline, Week 8)
- Core Period: Change From Baseline in Plasma Cortisol Levels by Adrenocorticotropic Hormone (ACTH) Stimulation Test(Baseline, 1 hour post-dose at Week 8)
- Core Period: Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8 LOCF(Baseline, Week 8)
- Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8(Baseline, Week 8)
- Core Period: Change From Baseline in Mean 24 Hour Ambulatory SBP at Week 8 as Measured by Ambulatory Blood Pressure Monitoring (ABPM)(Baseline, Week 8)
- Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP at Week 8(Baseline, every hour up to 24 hours post-dose at Week 8)
- Core Period: Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8 LOCF(Baseline, Week 8)
- Withdrawal Period: Change From Week 8 to Week 9 in MSDBP at Week 9, as Measured by OBP(From Week 8 to Week 9)
- Withdrawal Period: Change From Week 8 to Week 9 in MSSBP at Week 9 as Measured by OBP(From Week 8 to Week 9)