Clinical trial NCT00284128: AVE7688 in Patients With Mild to Moderate Blood Pressure
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hypertension
Keywords: Cardiovascular Disease C14
vascular disease C14.907
hypertension C14.907.489
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-01-31
Enrollment: 1940
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change from baseline in trough diastolic blood pressure at the end of week 12.
timeFrame: 12 weeks
Secondary outcomes:
measure: Change from baseline in trough systolic blood pressure at the end of week 12, percentages of responders after 12 week of treatment.
timeFrame: 12 weeks
measure: Evaluation of long term safety and tolerability of AVE7688 with particular attention to angioedema.
timeFrame: 12 months
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Buenos Aires
country: Argentina
facility: Sanofi-Aventis Administrative Office
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Santiago
country: Chile
facility: Sanofi-Aventis Administrative Office
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Athens
country: Greece
facility: Sanofi-Aventis Administrative Office
city: Causeway Bay
country: Hong Kong
facility: Sanofi-Aventis Administrative Office
city: Milano
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis Administrative Office
city: Kuala Lumpur
country: Malaysia
facility: Sanofi-Aventis Administrative Office
city: Mexico
country: Mexico
facility: Sanofi-Aventis Administrative Office
city: Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Warszawa
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Administrative Office
city: Singapore
country: Singapore
facility: Sanofi-Aventis Administrative Office
city: Midrand
country: South Africa
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Taipei
country: Taiwan
facility: Sanofi-Aventis Administrative Office
city: Istanbul
country: Turkey
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: