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

April 19, 2016 updated by: Sanofi

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1940

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Sanofi-Aventis Administrative Office
  • Brazil
      • Sao Paulo, Brazil
        • Sanofi-Aventis Administrative Office
  • Canada
      • Laval, Canada
        • Sanofi-Aventis Administrative Office
  • Chile
      • Santiago, Chile
        • Sanofi-Aventis Administrative Office
  • Germany
      • Berlin, Germany
        • Sanofi-Aventis Administrative Office
  • Greece
      • Athens, Greece
        • Sanofi-Aventis Administrative Office
  • Hong Kong
      • Causeway Bay, Hong Kong
        • Sanofi-Aventis Administrative Office
  • Italy
      • Milano, Italy
        • Sanofi-Aventis Administrative Office
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Sanofi-Aventis Administrative Office
  • Malaysia
      • Kuala Lumpur, Malaysia
        • Sanofi-Aventis Administrative Office
  • Mexico
      • Mexico, Mexico
        • Sanofi-Aventis Administrative Office
  • Netherlands
      • Gouda, Netherlands
        • Sanofi-Aventis Administrative Office
  • Poland
      • Warszawa, Poland
        • Sanofi-Aventis Administrative Office
  • Portugal
      • Porto Salvo, Portugal
        • Sanofi-Aventis Administrative Office
  • Russian Federation
      • Moscow, Russian Federation
        • Sanofi-Aventis Administrative Office
  • Singapore
      • Singapore, Singapore
        • Sanofi-Aventis Administrative Office
  • South Africa
      • Midrand, South Africa
        • Sanofi-Aventis Administrative Office
  • Spain
      • Barcelona, Spain
        • Sanofi-Aventis Administrative Office
  • Taiwan
      • Taipei, Taiwan
        • Sanofi-Aventis Administrative Office
  • Turkey
      • Istanbul, Turkey
        • Sanofi-Aventis Administrative Office
  • United States
    • New Jersey
      • Bridgewater, New Jersey, United States, 08807
        • Sanofi-Aventis Administrative Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ilepatril (2.5 mg ) once daily
AVE7688 oral administration
Drug: AVE7688
oral administration (capsules)
Other Names:
  • ilepatril
Experimental: ilepatril (10 mg) once daily
AVE7688 oral administration
Drug: AVE7688
oral administration (capsules)
Other Names:
  • ilepatril
Experimental: ilepatril (35 mg) once daily
AVE7688 oral administration
Drug: AVE7688
oral administration (capsules)
Other Names:
  • ilepatril
Experimental: ilepatril (50 mg) once daily
AVE7688 oral administration
Drug: AVE7688
oral administration (capsules)
Other Names:
  • ilepatril
Other: Losartan-potassium (100 mg) once daily
oral administration
Drug: Losartan-potassium
oral administration (capsules)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in trough diastolic blood pressure at the end of week 12.
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome 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.
Time Frame: 12 weeks
12 weeks
Evaluation of long term safety and tolerability of AVE7688 with particular attention to angioedema.
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2005

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

January 30, 2006

First Submitted That Met QC Criteria

January 30, 2006

First Posted (Estimate)

January 31, 2006

Study Record Updates

Last Update Posted (Estimate)

May 18, 2016

Last Update Submitted That Met QC Criteria

April 19, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DFI6032

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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