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
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 28, 2014