Double-blind, Randomized, Parallel-group, Dose Ranging, Multicenter Study to Evaluate the Efficacy and Safety of 2.5, 10, 35 and 50 mg AVE 7688 Once Daily, Using 100 mg Losartan-potassium Once Daily as Calibrator, for 12 Months Treatment, in Patients With Mild to Moderate Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 1,940
- 试验地点
- 1
- 主要终点
- Change from baseline in trough diastolic blood pressure at the end of week 12.
研究概览
简要总结
The primary objective is to assess the antihypertensive efficacy of 4 different AVE 7688 doses on the change from baseline in trough diastolic blood pressure at the end of week 12.
The secondary objectives are:
- To assess the antihypertensive efficacy of 4 different AVE 7688 doses on the change from baseline in trough systolic blood pressure at the end of week 12
- To compare the percentages of responders after 12 week of treatment
- To evaluate the long term safety and tolerability of AVE 7688 with particular attention to angioedema
详细描述
This study is a prospective multi-center, randomized, double-blind, active-controlled parallel-group, dose ranging study with 5 treatment groups (AVE7688 at 4 different dosages, and losartan-potassium 100 mg). There will be 3 study phases: placebo lead-in, treatment, and follow-up.
During the placebo lead-in phase (duration 3 to 4 weeks), patients will discontinue concomitant treatment with any antihypertensive or vasodilating agents and will receive single-blind placebo until randomization. Patients who meet the inclusion and exclusion criteria will be randomized to receive once-daily oral doses of either 2.5, 10, 35 or 50 mg AVE7688, or 100 mg losartan-potassium.
The treatment phase will consist of two parts: an efficacy evaluation period, with a 2 week titration period (from randomization to week 2, visit T1 to visit T3) up to 12 weeks, followed by a long-term safety evaluation period until the end of week 52. Antihypertensive treatment such as diuretics, beta blockers or calcium channel blockers can be introduced or re-introduced if indicated during the long term safety evaluation period but angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) are not permitted.
An additional visit (visit F1) will occur two weeks after the last dose of study medication.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with mild-to-moderate, treated or untreated, essential hypertension, as defined by the JNC VII (Joint National Committee on the Prevention, Detection, Evaluation, and
- •Treatment of High Blood Pressure, Seventh report ) guidelines who meet the following BP eligibility criteria:
- •mean SeSBP (Seated systolic blood pressure) ≥140 mm Hg and <180 mm Hg and mean SeDBP (Seated diastolic blood pressure) ≥90 mm Hg and <110 mm Hg at two consecutive qualifying visits in the placebo lead-in phase
- •variability between the mean BP measurements on the 2 consecutive qualifying visits is less or equal 7 mm Hg for SeDBP.
排除标准
- •Refusal or inability to give informed consent
- •Patients who have previously been treated with AVE7688
- •Patients who cannot stop their anti-hypertensive treatment
- •Known history of secondary hypertension, including patients with endocrine disorders such as pheochromocytoma, active hyperthyroidism, or untreated hypothyroidism
- •Severe hypertension
- •Women of child bearing potential, who have a positive serum pregnancy test, or who do not agree to use an accepted method of contraception
- •Women who are breast feeding
- •Patients with non-cardiac progressive fatal disease
- •Patients with immunological or hematological disorders
- •Requirement for concomitant treatment that could bias the primary evaluation
- •Unstable insulin-dependent diabetes mellitus
- •History of stroke, intracranial hemorrhage or transitory ischemic attack within the previous year
- •Likelihood of poor compliance both with treatment and study design
- •Patient is the investigator, sub-investigator, research assistant, pharmacist, study coordinator, or other staff member or relative there of directly involved in the conduct of the study
- •Administration of any investigational drug within the preceding 30 days
- •Abuse of drugs or alcoholic beverages within 1 year prior to the start of the study
- •Patients taking herbal or dietary compounds that have the potential to influence blood pressure
- •Contraindications to losartan-potassium as per local package insert
- •History of hypersensitivity or angioedema with ACE inhibitors or NEP inhibitors, patients with hereditary or idiopathic angioedema, patients with allergic reaction in which urticaria or angioedema was the manifestation
- •Impaired hepatic function
- •Known unilateral or bilateral renal artery stenosis
- •Serum potassium > 5.5 mmol/L
- •Impaired renal function
研究组 & 干预措施
ilepatril (2.5 mg ) once daily
AVE7688 oral administration
干预措施: AVE7688 (Drug)
ilepatril (10 mg) once daily
AVE7688 oral administration
干预措施: AVE7688 (Drug)
ilepatril (35 mg) once daily
AVE7688 oral administration
干预措施: AVE7688 (Drug)
ilepatril (50 mg) once daily
AVE7688 oral administration
干预措施: AVE7688 (Drug)
Losartan-potassium (100 mg) once daily
oral administration
干预措施: Losartan-potassium (Drug)
结局指标
主要结局
Change from baseline in trough diastolic blood pressure at the end of week 12.
时间窗: 12 weeks
次要结局
- Change from baseline in trough systolic blood pressure at the end of week 12, percentages of responders after 12 week of treatment.(12 weeks)
- Evaluation of long term safety and tolerability of AVE7688 with particular attention to angioedema.(12 months)