E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Congestive heart failure patients presenting as Cheyne-Stokes Breathing Syndrome |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008501 |
E.1.2 | Term | Cheyne-Stokes respiration |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess:
-The activity of 4 doses of AVE0657, 40, 100, 160 and 320 mg/day, in comparison to placebo in patients with CSBS
-The safety and the tolerability by monitoring of adverse events, clinical laboratories, vital signs, respiratory parameters and ECG.
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E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetic parameters of AVE0657 in patients with CSBS |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Apnea Hypopnea Index (AHI), AHI will be compared as change on Day 2 to baseline AHI measurement. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 4 |