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

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.

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