E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients suffering from Obstructiv-Sleep Apnea Hypopnea Syndrome (OSAHS) |
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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 | 10055577 |
E.1.2 | Term | Obstructive sleep apnea syndrome |
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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 and ECG.
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E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetic parameters of AVE0657 in patients with Obstructive Sleep Apnea Hypopnea Syndrome. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Main inclusion criteria:
-OSAHS with an AHI (number/hour) ≥15 and up to 35 including ≥60% obstructive or mixed AH.
-Daytime sleepiness or at least 2 of the following: choking/gasping during sleep, recurrent awakenings from sleep, daytime fatigue, unrefreshing sleep, impaired concentration along with irritability or mood swings
Other inclusion criterias: •Related to Subjects: Out-patients ≥18 years of age or the legal age of consent in the area where the study is being done male and female patients but less then 75 years. •Related to sleep disorders: Each subject must have the history of OSAHS for at least one month preceding the study visit.
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E.4 | Principal exclusion criteria |
•Medical condition that may interfere with the study conduct and/or assessment:
-Patients treated by CPAP, oral appliance during 4-week period prior to randomization.
- Chronic respiratory disease (COPD, pulmonary fibrosis or asthma) or FEV/FVC <= 55% by history or PaCO2 <34 mmHg (5 KPa) or PaCO2 >45 mmHg (6 KPa) or PaO2 <67 mm Hg (9 KPa)
- Patient treated with concomitant medication that are known to be strong or moderate CYP3A4 inhibitors. A list is proposed in Appendix C
-Body mass index (BMI) of ≤20 kg/M2 or ≥35 kg/M2
-Surgical procedure to correct apnea within the last 3 months.
•Related to subjects: -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.
-Night shift workers and individuals who napped 3 or more times per week over the preceding month.
-Consumption of xanthine-containing beverages (eg, 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 unwilling or unable to provide written, signed and dated informed consent.
-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 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. This includes the following criteria: - 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 3 |