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AVE7688 in Patients With Mild to Moderate Blood Pressure (RAVEL-1)

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00284128
First received: January 30, 2006
Last updated: July 25, 2011
Last verified: July 2011
History of Changes
  Purpose

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

Condition Intervention Phase
Hypertension
 Drug: AVE7688
Drug: Losartan-potassium
 Phase 2
Phase 3

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Change from baseline in trough diastolic blood pressure at the end of week 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in trough systolic blood pressure at the end of week 12, percentages of responders after 12 week of treatment. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Evaluation of long term safety and tolerability of AVE7688 with particular attention to angioedema. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 1940
Study Start Date: December 2005
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AVE7688 - Dose 2.5 mg Drug: AVE7688
oral administration (capsules)
Experimental: AVE7688 - Dose 10 mg Drug: AVE7688
oral administration (capsules)
Experimental: AVE7688 - Dose 35 mg Drug: AVE7688
oral administration (capsules)
Experimental: AVE7688 - Dose 50 mg Drug: AVE7688
oral administration (capsules)
Losartan-potassium 100 mg Drug: Losartan-potassium
oral administration (capsules)

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00284128

  Show 21 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Trial Transparency Team, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00284128     History of Changes
Other Study ID Numbers: DFI6032
Study First Received: January 30, 2006
Last Updated: July 25, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Cardiovascular Disease C14
vascular disease C14.907
hypertension C14.907.489

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Losartan
Anti-Arrhythmia Agents
Cardiovascular Agents
 Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013