E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Insomnia characterized by sleep maintenance difficulties |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027590 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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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 compare the potential for next-day residual effects of volinanserin 2 mg/day and lormetazepam 1 mg/day by measuring the sleepiness in the morning using the patient’s sleep questionnaire during 4 weeks of treatment in patients with chronic primary insomnia and sleep maintenance difficulties. |
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E.2.2 | Secondary objectives of the trial |
• To compare the clinical safety of both products, including the potential for rebound insomnia and withdrawal symptoms after treatment discontinuation. • To compare the efficacy of both products on subjective sleep parameters (patient reported (pr)-Wake time After Sleep Onset (WASO), pr-Total Sleep Time (TST), pr-Number of Awakenings (NAW), pr-Sleep Onset Latency (SOL), Quality of Sleep (QoS), refreshing. (QoS) • To compare the effects of both products on patient’s daytime functioning using the Sleep Impact Scale (SIS) after 4 weeks of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written, signed and dated informed consent obtained (for patients accepting pharmacogenetic testing, specific written, signed and dated informed consent obtained); 2. Primary Insomnia according to DSM-IV-TR criteria (Appendix A), with predominantly difficulty in maintaining sleep for at least one month preceding the study visit, and having clinically significant distress or impairment in social, occupational or other important areas of functioning. |
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E.4 | Principal exclusion criteria |
•Exclusion criteria related to study methodology 1. Patients younger than 18 years; 2. Inpatients; 3. Based on patient’s information, the patient has spent less than 6.5 hours or more than 9.0 hours, in bed, each night, over the preceding two weeks; 4. Based on patient’s information, the patient complains of less than one hour of wakefulness after sleep onset for at least 3 nights per week over the preceding month; 5. Based on patient’s sleep questionnaire administered each morning during the run-in period, mean pr-WASO < 45 min (calculated on at least 4 nigths); 6. Based on patient’s sleep questionnaire administered each morning during the run-in period, mean pr-TST > 7 hours or < 3 hours (calculated on at least 4 nigths); 7. Based on patient’s sleep questionnaire administered each morning during the run-in period, mean pr-SOL > 30 min (calculated on at least 4 nigths); 8. Women of childbearing potential (less than 2 years of postmenopausal or not surgically sterile) without a negative urine β-hCG test prior to entry into the study and who do not employ an acceptable method of birth control for this study for one month prior to entry into the run-in, throughout the study, and one month after study medication administration is stopped. Acceptable methods are the following: IUDs, depot, implant and trans-dermal estrogens-progesterones alone, combined oral contraceptives, sterilization, and double barrier methods in conjonction with permicide, vasectomized partner, and sexual abstinence. (Unless not acceptable by local health authorities); 9. Females who are pregnant or breastfeeding; 10. Night shift workers and individuals who nap 3 or more times per week over the preceding month (a nap being defined by an intentional sleep of more than 20 minutes); 11. Consumption of xanthine-containing beverages (i.e., tea, coffee or cola) that comprises more than 5 cups or glasses per day; 12. Patient unable to participate for the entire duration of the study or unable to complete study questionnaires or, in the opinion of the investigator has the potential to be non compliant with the obligations inherent in trial participation; 13. Participation in another clinical trial within 1 month before the screening visit; 14. Participation (randomization) in a previous volinanserin trial; 15. Based on medical history and patient’s information: primary hypersomnia, narcolepsy, breathing related sleep disorders, circadian rhythm sleep disorder, parasomnia (e.g., somnambulism), dyssomnia not otherwise specified (i.e., periodic leg movement); 16. Current severe neuropsychiatric disorders (i.e., psychosis, obsessive compulsive disorder, major depression, anxiety disorders, panic disorders, dementia of Alzheimer’s or vascular type) according to DSM-IV-TR criteria or mental retardation; 17. Insomnia secondary to a general medical condition; 18. Substance dependence or substance abuse within the last year (except nicotine, DSM-IV-TR criteria); 19. Acute or unstable chronic disease that in the opinion of the Investigator, would compromise the patient’s safety or successful participation in the study or that might interfere with the evaluation of study medication; 20. Evidence of any significant laboratory or ECG finding at screening which the investigator judges incompatible with the investigation of a new chemical entity; 21. Use of any over-the-counter (OTC) medications (including tryptophan, valerian, kavakava, melatonin and St John’s Wort) or prescription sleep medications including hypnotics and sedatives and anxiolytics within 1 week or 5 half-lives (whichever is longer) before screening; 22. Use of any substance with psychotropic effects or properties known to affect sleep/wake, including but not limited to: antipsychotics, morphine/opioid derivatives, antihistaminics, stimulants, antidepressants, clonidine, within 1 week or 5 half-lives (whichever is longer) before screening. •Exclusion criteria related to volinanserin 23. Lifetime history of diverticulitis (or sigmoiditis) • Exclusion criteria related to lormetazepam 24. Certain muscular disorders (i.e.; myasthenia gravis); 25. Narrow angle glaucoma; 26. Hypersensitivity to benzodiazepines.
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E.5 End points |
E.5.1 | Primary end point(s) |
Sleepiness in the morning measured on a visual analog scale of the patient’s sleep questionnaire. (“Do you feel sleepy this morning?”, 100 mm-VAS: very sleepy – not at all sleepy). |
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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 | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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) | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | Yes |
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 | 1 |
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 years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |