Sleep Laboratory Study to Investigate the Safety and Efficacy of Neu-P11 in Primary Insomnia Patients

A Double-blind, Parallel Group, Randomized, Placebo Controlled Sleep Laboratory Study of Efficacy and Safety of Neu-P11 in Insomnia Patients Aged 18-80

This is a phase II study. It is conducted using a randomized, double-blind, 3-arm placebo controlled, parallel group design. Eligible patients will be randomized in a 1:1:1 ratio to receive Neu-P11 20 mg, Neu-P11 50 mg or placebo for 4 weeks The objective of this study is to assess the efficacy of Neu-P11 (20 and 50mg) on sleep continuity parameters in insomnia patients aged 18-80 years, following the first two nights (immediate effect) and at the end of 4 weeks of double-blind treatment. The primary efficacy endpoint in this study is Latency to Persistent Sleep (LPS) measured by polysomnogram (PSG) at the first two nights of treatment (nights 15-16 of the study; mean of two consecutive nights recordings). The secondary endpoints are number of awakenings after sleep onset and the duration of wake after sleep onset measured by PSG at the first two nights of treatment (nights 15-16 of the study; mean of two consecutive nights recordings).

Inclusion Criteria:

1. Male or female and aged 18-80 years (both ages included).

2. Suffering from primary insomnia according to DSM-IV criteria (307.42 primary insomnia, Appendix 25.1) (based on a Sleep History Questionnaire (SHQ) that is given to the patient at Visit Day 0, Appendix 25.1).

3. Reported subjective sleep latency of at least 30 minutes on at least three nights per week for at least one month and subjective WASO of at least 45 minutes per night on at least 3 nights per week for at least one month (based on the SHQ).

4. Subjects with habitual bed time within the range of 21:00-01:00 (inclusive), as reported by the subject during screening on Day 0.

5. If female of childbearing potential, using a reliable method of contraception during the entire study duration and for at least 3 months after study drug intake.

6. Have not been using benzodiazepine (BZD) and non-BZD hypnotics or melatoninergic drugs for the past 2 weeks or more prior to Screening.

7. Have not been using psychotropic treatments for the past 3 months or more prior to Screening.

8. Are stabilized on non-psychotropic treatments for more than 3 months prior to Screening.

9. Are willing to sign a written informed consent to participate in the study.

   • After initial screening, recruited patients will enter a 2 week placebo baseline/eligibility period.

   Patients will be admitted into a sleep lab and will continue to the double blind treatment phase if polysomnography (PSG) results meet the following criteria:

10. Mean LPS ≥30 minutes on both PSG screening nights, with neither night <15 minutes.

11. Mean total sleep time (TST) ≤390 minutes, or mean WASO ≥30 minutes on both of the 2 PSG screening nights, with neither night <15 minutes.

Exclusion Criteria:

1. According to DSM IV, subjects belonging to the following groups are excluded: 780.59 (breathing related sleep disorder); 307.45 (circadian rhythm sleep disorder); 307.47 (dyssomnia not otherwise specified); 780.xx (sleep disorder due to general medical condition)
2. Subjects suffering from insomnia secondary to other causes according to the sleep history questionnaire.
3. Subjects with sleep disorders detected during PSG inclusion/habituation night, such as sleep apnea/hypopnea and periodic leg movement syndrome (with arousal) (PLMAI>10 and/or AHI > 10 per hour).
4. Use of psychotropic treatments for the past 3 months and during the study.
5. Use of strong CYP inhibitors in the preceding 3 months and during the study
6. Use of benzodiazepines or other hypnotics during preceding two weeks (including all benzodiazepines; zopiclone, zolpidem, zaleplon, barbiturates, buspirone and hydroxyzine).
7. Alcohol intake - no more than 2 alcoholic drinks per day and any consumption less than 2 hours before study drug intake.
8. Immunosuppressive medication in the preceding 3 months and during the study
9. Severe neurological, psychiatric disorders especially psychosis, anxiety and depression
10. Intercurrent acute or chronic somatic diseases likely to interact with sleep (for example: chronic pain from any etiology, benign prostatic hypertrophy likely to require surgery in the coming six months)