AVE7688 in Patients With Mild to Moderate Blood Pressure

Hypertension Clinical Trial

— RAVEL-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00284128
• Other study ID #: DFI6032
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 30, 2006
• Last updated: July 25, 2011
• Start date: December 2005
• Est. completion date: March 2008

Study information

• Verified date: July 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 1940
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with mild-to-moderate, treated or untreated, essential hypertension, as defined by the JNC VII guidelines who meet the following BP eligibility criteria:

• mean SeSBP =140 mm Hg and <180 mm Hg and mean SeDBP =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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• AVE7688
oral administration (capsules)
• Losartan-potassium
oral administration (capsules)

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Canada	Sanofi-Aventis Administrative Office	Laval
Chile	Sanofi-Aventis Administrative Office	Santiago
Germany	Sanofi-Aventis Administrative Office	Berlin
Greece	Sanofi-Aventis Administrative Office	Athens
Hong Kong	Sanofi-Aventis Administrative Office	Causeway Bay
Italy	Sanofi-Aventis Administrative Office	Milano
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Malaysia	Sanofi-Aventis Administrative Office	Kuala Lumpur
Mexico	Sanofi-Aventis Administrative Office	Mexico
Netherlands	Sanofi-Aventis Administrative Office	Gouda
Poland	Sanofi-Aventis Administrative Office	Warszawa
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
Singapore	Sanofi-Aventis Administrative Office	Singapore
South Africa	Sanofi-Aventis Administrative Office	Midrand
Spain	Sanofi-Aventis Administrative Office	Barcelona
Taiwan	Sanofi-Aventis Administrative Office	Taipei
Turkey	Sanofi-Aventis Administrative Office	Istanbul
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Chile,  Germany,  Greece,  Hong Kong,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Poland,  Portugal,  Russian Federation,  Singapore,  South Africa,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in trough diastolic blood pressure at the end of week 12.		12 weeks	No
Secondary	Change from baseline in trough systolic blood pressure at the end of week 12, percentages of responders after 12 week of treatment.		12 weeks	No
Secondary	Evaluation of long term safety and tolerability of AVE7688 with particular attention to angioedema.		12 months	Yes