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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022437 |
E.1.2 | Term | Insomnia |
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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 demonstrate efficacy of M100907 2 mg/day in comparison to placebo as change from baseline to 3 months for Sleep Maintenance Insomnia using patient reported Wake After Sleep Onset pr-WASO |
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E.2.2 | Secondary objectives of the trial |
- To assess efficacy of M100907 2 mg/day in comparison to placebo as change from baseline to 6, 12 mo.s for Sleep Maintenance Insomnia using pt reported Wake After Sleep Onset pr-WASO - To evaluate patient s daytime functioning on M100907 2 mg/day against placebo using change from baseline to 3 months in the General Productivity Domain score of the Functional Outcomes of Sleep Questionnaire FOSQ . - To assess efficacy of M100907 2mg/day in comparison to placebo as change from baseline to 3, 6 and 12 months on other parameters of patient s sleep questionnaire. - To assess long term clinical safety and tolerability of M100907 2 mg/day in comparison to placebo during the 12 months of treatment - in Sub-population type II Diabetes Mellitus with SMI 1- Efficacy To demonstrate improved glycemic control in patients with type II diabetes mellitus and sleep main-tenance insomnia using change from baseline of HbA1C at 6 and 12 months. 2 -Safety and tolerability |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Related to patients 1. Out-patients 18 years of age or older or the legal age of consent in the area where the study is being performed. 2. Woman of childbearing potential less than two years post-menopausal or not surgically sterile , must have a negative urine pregnancy test at screening and must use a highly effective method of birth control, which is defined as those which result in a low failure rate i.e. less than 1 per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, IUDs containing hormones, sexual abstinence unless not acceptable by the local health authorities or vasectomised partner. Related to sleep disorders 3. Each patient must have primary insomnia based on criteria DSM IV-TR with predominant complaints of difficulty in maintaining sleep nocturnal awakenings or early morning awakenings , 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. 4. Based on patient s information, the patient must complain of at least one hour of wakefulness after sleep onset for at least 4 or more nights per week over the preceding month. 5. Based on patient s information, the patient has spent at least 6.5 hours and not more than 9.0 hours, in bed, each night, over the preceding two weeks. 6. 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. To be included patient s answer should be either 2 Somewhat interfering , or 3 Much , or 4 Very Much Interfering at both visits. 7. Based on the information recorded in the patient s sleep questionnaire during the screening week preceding the randomization the following criteria must be present In the Screening Period 5 10 days more than a half 50 of nights must have WASO or equal to 60 min. TST or equal to 7 hours and or equal to 3 hours on 3-worst screening nights. Excluding one night in the Screening Period 5 10 days , with the highest Sleep Onset Latency SOL value, the mean SOL for the Screening Period must be or equal to 30 min. Related to Type II Diabetes Mellitus 8. Patients with type II diabetes WHO definition 1 must have been on an oral hypoglycemic agent s and/or insulin for at least 3 months prior to the Screening Visit stable regimen for at least one month prior to Screening Visit . / |
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E.4 | Principal exclusion criteria |
Related to patients 1. Females who are lactating or who are pregnant. 2. Night shift workers, and individuals who nap 3 or more times per week over the preceding month. 3. Consumption of xanthine-containing beverages i.e. tea, coffee, or cola comprising usually more than 5 cups or glasses per day. 4. Participation in another trial having received study medication within one month before the screening visit. 5. Body mass index o uguale a 33 calculated from patient s height m and weight kg ; weight kg /height m . 6. 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 supplement with valerian root or prescription sleep medication, including hypnotics and sedatives, and anxiolytics, within one week or five half-lives whichever is longer , prior to screening. 7. Use of any substance with psychotropic effects or properties know to affect sleep/wake, including, but not limited to neuroleptics, morphine/opioid derivatives, sedative antihistamines, stimulants, antidepressants, clonidine, within one week or five half-lives whichever is longer , prior to screening. 8. Patients unable to complete the study questionnaires. 9. Patients unwilling to provide written, signed and dated informed consent must not be included in the study. 10. 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. Related to sleep disorders 11. 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. Related to concomitant illnesses 12. Patients presenting with acute or chronic pain resulting in insomnia. 13. Patients with current psychiatric disturbances according to DSM IV 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. 14. Patients with mental retardation or dementia. 15. Patients with a history of epilepsy or seizures not including benign neonatal and childhood convulsions . 16. 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. 17. Clinically significant and abnormal ECG including QTcF o uguale a 500 ms . 18. Serious head injury or stroke within the past year. 19. Positive qualitative urine drug screen opiates, cocaine, amphetamine, cannabinoids, barbiturates, phencyclidine, benzodiazepines, methadone, propoxyphene , at screening. Related to Diabetes Mellitus Type II 20. HbA1C levelof or equal to 9.5 at the Screening Visit. 21. HbA1C level of or equal to 6.5 at the Screening Visit. Note diabetic patients with HbA1C level of or equal to 6.5 may be included in the main study population . 22. Fasting Plasma Glucose or equal to 250 mg/dL 14.0 mmol/L at the Screening Visit 23. Patients with poorly controlled diabetes; i.e., a history of hospitalization for ketoacidosis within the past 12 months |
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E.5 End points |
E.5.1 | Primary end point(s) |
Sleep Maintenance Insomnia Efficacy Change from baseline to 3 months of the mean patient reported WASO derived from patient s sleep questionnaire |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
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 | 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 | 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.8.5 | 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 | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |