E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sleep maintenance insomnia. |
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MedDRA Classification |
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 efficacy of eplivanserin 5mg/day in comparison to placebo after 6 and 12 weeks of treatment on Sleep Maintenance Insomnia using patient sleep questionnaires (pr-WASO). |
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E.2.2 | Secondary objectives of the trial |
12 -week double-blind treatment period: Main Secondary objective: • To evaluate patient’s daytime functioning using the Functional Outcomes of Sleep Questionnaire (“General Productivity” domain) with eplivanserin 5mg/day as compared to placebo after 6 and 12 weeks of treatment
Other Secondary objectives: • To evaluate residual effects •To evaluate the clinical safety and tolerability • Health Outcomes: To evaluate the effect on patient’s ability to work using the work limitation questionnaire.
Open treatment phase extension: 40 weeks duration • To evaluate patient’s daytime functioning using the Functional Outcomes Sleep Questionnaire with eplivanserin 5mg/day. • To evaluate the clinical safety. • To assess the effect on sleep following abrupt discontinuation of study treatment (during run-out period). • Health Outcomes: to evaluate the effect on patient’s ability to work using Work Limitation Questionnaire.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Out-patients aged ≥ 18 years. • Diagnosis of primary insomnia based on criteria (DSM-IV-TR) with predominant complaints of difficulty in initiating or maintaining sleep (nocturnal awakenings), or nonrestorative sleep for at least one month preceding the study visit.
• Disturbances of sleep maintenance: Based on patient’ s information: - Patient has spent at least 6.5 hours and no more than 9.0 hours, in bed, each night, over the preceding two weeks. - Patient must complain of at least one hour of wakefulness after sleep onset for at least 3 nights per week over the preceding month.
•Patient must report impact daytime functioning associated with sleep maintenance insomnia as measured by question 3 of Insomnia Severity Index at screening and randomization visits. Based on the information recorded in the patient’s diary during the screening week preceding the randomization the following criteria must be present: a) Mean WASO per night > 60mn during screening period (7 days) and no period of WASO < 45mn on each screening night. However, two nights with WASO < 45 min during screening period is acceptable. In addition, two lowest WASO values will be excluded from the calculation of the mean WASO. b) TST ≤ 7 hours and ≥ 3 hours on 3-worst screening nights. c) Mean SOL per night have to be ≤ 30 mn during the screening period. One highest SOL value will be excluded from the calculation of mean SOL.
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E.4 | Principal exclusion criteria |
• Related to study methodology: 1. Females who are lactating or who are pregnant, 2. Woman of childbearing potential (less than two years post-menopausal or not surgically sterile), with a positive serum beta-human chorionic gonadotropin (bêta HCG) pregnancy test at screening and not using an acceptable form of contraception (e.g., birth control pill, intra-uterine device, injection of Depo- ProveraTM ,double-barrier method, abstinence), 3. Patients presenting with acute or chronic pain resulting in insomnia, 4. Patients with current psychiatric disturbances according to DSM-IV-TR criteria including but not limited to psychosis and /or 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 and /or bipolar disorder, 5. Body mass index >32 calculated from patient’s height (m) and weight (kg); weight (kg)/height (m²), 6. Patients with mental retardation or dementia, 7. Patients with a history of epilepsy or seizures (not including benign neonatal and childhood convulsions), 8. Evidence of any 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, 9. Clinically significant and abnormal ECG (including QTc ≥ 500ms), 10. A positive test for hepatitis B (HBs antigens) or C (HCV antibodies), 11. Serious head injury or stroke within the past year, 12. Positive qualitative urine drug screen (opiates, cocaine, amphetamine, cannabinoids, barbiturates, phencyclidine, benzodiazepines, methadone, propoxyphene), at screening, 13. Consumption of xanthine-containing beverages (i.e. tea, coffee, or cola) comprising usually more than 5 cups or glasses per day, 14. Use of any over-the-counter including tryptophan, valerian root (Valeriana officinalis), kava (Piper methysticum Forst), melatonin, St John’s Wort (Hypericum perforatum), Alluna (herbal sleep supplement with valerian root) or prescription sleep medication, including hypnotics and sedatives (N05C), and anxiolytics (N05B), within one week or five half-lives (whichever is longer), prior to screening, 15. Use of any substance with psychotropic effects or properties known to affect sleep/wake, including, but not limited to: neuroleptics (N05A), morphine/opioid derivatives (N02A), sedative antihistamines (R06A), stimulants (N06B) antidepressants (N06A), clonidine, within one week or five half-lives (whichever is longer), prior to screening, 16. Participation in another trial within two months before the screening visit, 17. Patients unable to complete the study questionnaire, 18. Patients 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, 19. Written, signed and dated informed consent not obtained from each patient, 20. Patient not able to understand and follow the requirements of the study and to comply. 21. Lifetime history of diverticulitis or sigmoiditis
• Related to sleep disorders: 1. Night shift workers, and individuals who nap 3 or more times per week over the preceding month, 2. History of (i) primary hypersomnia, (ii) narcolepsy, (iii) breathing-related sleep disorder, (iv) circadian rhythm sleep disorder, (v) parasomnia (e.g. somnambulism), (vi) dyssomnia not otherwise specified, i.e. periodic leg movement syndrome.
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E.5 End points |
E.5.1 | Primary end point(s) |
Wake time after sleep onset using patient's sleep questionnaire (pr-WASO) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
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 | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |