AVE7688 in Patients With Mild to Moderate Blood Pressure

Phase 2

Completed

Conditions: Hypertension

Interventions: Drug: AVE7688
Drug: Losartan-potassium

Registration Number: NCT00284128

Lead Sponsor: Sanofi

Brief Summary: 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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1940

Inclusion Criteria

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.

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ilepatril (2.5 mg ) once daily	AVE7688	AVE7688 oral administration
ilepatril (35 mg) once daily	AVE7688	AVE7688 oral administration
ilepatril (50 mg) once daily	AVE7688	AVE7688 oral administration
Losartan-potassium (100 mg) once daily	Losartan-potassium	oral administration
ilepatril (10 mg) once daily	AVE7688	AVE7688 oral administration

Primary Outcome Measures

Name	Time	Method
Change from baseline in trough diastolic blood pressure at the end of week 12.	12 weeks

Secondary Outcome Measures

Name	Time	Method
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