A double-blind, randomized, placebo-controlled, study evaluating the safety and activity of four escalating single doses of AVE0657 in congestive heart failure patients presenting as Cheyne-Stokes Breathing Syndrome

• Conditions: Congestive heart failure patients presenting as Cheyne-Stokes Breathing Syndrome; MedDRA version: 9.1Level: LLTClassification code 10008501Term: Cheyne-Stokes respiration

• Registration Number: EUCTR2007-002172-34-DE
• Lead Sponsor: sanofi-aventis recherche & développement

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-09-07
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

-Presence of Congestive heart failure (CHF) assessed by history of echocardiography data and New York heart Association (NYHA) class II-III and of typical cyclic crescendo and decrescendo change in breathing amplitude AHI =10 and <60 and majority of the apneas to be =60% central in origin. This will be the main inclusion criteria and the following will be additional criteria.

-Male and female out-patients =18 years of age or the legal age of consent in the area where the study is being done.

-Each patient must have history of CSBS at least one month preceding the study visit.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Medical condition which may interfere with the study conduct and/or assessment:
*Patient on supplemental oxygen

-Refusal or inability to give informed consents to participate in the study.

- Patient treated with concomitant medication that are known to be strong or moderate CYP3A4 inhibitors. A list is proposed on Appendix C.

-Women of childbearing potential without effective contraceptive measures, lactating or who are pregnant.

-Inability to meet some specific protocol requirements (eg, need for spending 2 nights in Sleep Laboratory).

-Subject is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

•Related to patients:
-Night shift workers and individuals who napped 3 or more times per week over the preceding month.

-Consumption of xanthine-containing beverages (ie, tea, coffee, or cola) comprising usually more than 5 cups or glasses per day.

-Participation in another trial having received study medication within two months before the screening visit.

-Subjects who are unable to participate for the entire duration of the study, or in the opinion of the investigator, are likely to be non-compliant with the obligations inherent in the trial participation.

- Patient adult under legal guardianship

•Related to concomitant illnesses:

-Subjects presenting with acute or chronic pain resulting in sleep disturbance.

-Subjects with current active psychiatric disturbances according to DSM IV criteria including but not limited to psychosis, schizophrenia, bipolar disorder, obsessive-compulsive disorder, major depression, anxiety disorders, panic disorders, eating disorder, alcohol or substance abuse or dependence -except nicotine-, or a history of lifetime psychosis.

-Subjects with mental retardation or dementia of Alzheimer’s or vascular type.

-Subjects with a history of epilepsy or seizures (not including benign neonatal and childhood convulsions).

-Evidence of any Laboratory abnormality, clinically significant severe or unstable, acute or chronically progressive medical or surgical disorder, or any condition that may interfere with the absorption, metabolism, distribution or excretion of the study drug, or may affect patient safety.

- Creatinine clearance level =50 mL/min
- Abnormal liver function tests (ALT or AST >2 times the upper limit of the normal range)
- Hypertension poorly controlled by well-managed treatment, unstable, refractory or severe hypertension (supine or sitting systolic =180 / diastolic =110 mmHg)
- Past history of stroke within the previous 6 months
- Past history of myocardial infarction within the previous 6 months

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess:<br><br>-The activity of 4 doses of AVE0657, 40, 100, 160 and 320 mg/day, in comparison to placebo in patients with CSBS <br><br>-The safety and the tolerability by monitoring of adverse events, clinical laboratories, vital signs, respiratory parameters and ECG.<br>;Secondary Objective: To evaluate the pharmacokinetic parameters of AVE0657 in patients with CSBS;Primary end point(s): Apnea Hypopnea Index (AHI), AHI will be compared as change on Day 2 to baseline AHI measurement.