Hypertension
Conditions
Keywords
Cardiovascular Disease C14, vascular disease C14.907, hypertension C14.907.489
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.
Interventions
DRUGAVE7688
oral administration (capsules)
DRUGLosartan-potassium
oral administration (capsules)
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in trough diastolic blood pressure at the end of week 12. | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Argentina, Brazil, Canada, Chile, Germany, Greece, Hong Kong, Italy, Malaysia, Mexico, Netherlands, Poland, Portugal, Russia, Singapore, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United States
Outcome results
None listed