ave7688 in patients with mild to moderate blood pressure

Conditions: Hypertension

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

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.

Eligibility criteria:
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

Keywords: cardiovascular disease c14 vascular disease c14.907 hypertension c14.907.489