Primary Insomnia
Conditions
Keywords
sleep latency, Sleep maintenance, Sleep fragmentation, Polysomnography
Brief summary
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).
Interventions
DRUGNeu-P11
1 tablet daily 1-2 before bed time for 28 days of double blind treatment
Sponsors
Neurim Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Latency to Persistent Sleep | 2 days | The primary efficacy parameter is Latency to persistent sleep (LPS) measured by the PSG at the first two nights (immediate effect) of the double blind treatment period. LPS was summarized at baseline and after two days double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. For each treatment group, the mean score at the end of the two days was compared, adjusting for the baselinescore. An ANCOVA model was used. Lower score indicates reduction in latency to persistent sleep and thus considered improvement |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Awakenings (NOA) | 28 days | The secondary efficacy parameter is number of awakenings (NOA) measured by the PSG after 28 nights of the double blind treatment period. NOA was summarized at baseline and after 28 days double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. For each treatment group, the mean score at the end of the 28 nights was compared, adjusting for the baseline score. An ANCOVA model was used. Lower score indicates less awakenings and thus considered improvement. |
| Duration of Wake After Sleep Onset (WASO) | 28 days | The secondary efficacy parameter is the duration of wake after sleep onset (WASO) measured by the PSG after 28 nights of the double blind treatment period. WASO was summarized at baseline and after 28 days double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. For each treatment group, the mean score at the end of the 28 nights was compared, adjusting for the baseline score. An ANCOVA model was used. Lower score indicates less waking time and thus considered improvement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neu-P11 20mg Neu-P11 dose of 20 mg
Neu-P11: 1 tablet daily 1-2 before bed time for 28 days of double blind treatment | 45 |
| Neu-P11 50mg Neu-P11 dose of 50 mg
Neu-P11: 1 tablet daily 1-2 before bed time for 28 days of double blind treatment | 47 |
| Placebo matching placebo
Neu-P11: 1 tablet daily 1-2 before bed time for 28 days of double blind treatment | 45 |
| Total | 137 |
Baseline characteristics
| Characteristic | Neu-P11 50mg | Neu-P11 20mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 13.7 | 50.4 years STANDARD_DEVIATION 16.16 | 51.1 years STANDARD_DEVIATION 14.52 | 49.6 years STANDARD_DEVIATION 14.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 14 Participants | 12 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 31 Participants | 33 Participants | 98 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 14 Participants | 11 Participants | 37 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 31 Participants | 32 Participants | 98 Participants |
| Sex: Female, Male Female | 36 Participants | 28 Participants | 33 Participants | 97 Participants |
| Sex: Female, Male Male | 11 Participants | 17 Participants | 12 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 47 | 0 / 45 |
| other Total, other adverse events | 8 / 45 | 3 / 47 | 0 / 45 |
| serious Total, serious adverse events | 0 / 45 | 0 / 47 | 0 / 45 |
Outcome results
Primary
Latency to Persistent Sleep
The primary efficacy parameter is Latency to persistent sleep (LPS) measured by the PSG at the first two nights (immediate effect) of the double blind treatment period. LPS was summarized at baseline and after two days double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. For each treatment group, the mean score at the end of the two days was compared, adjusting for the baselinescore. An ANCOVA model was used. Lower score indicates reduction in latency to persistent sleep and thus considered improvement
Time frame: 2 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neu-P11 20mg | Latency to Persistent Sleep | -22.7 minutes | Standard Deviation 27.39 |
| Neu-P11 50mg | Latency to Persistent Sleep | -39.1 minutes | Standard Deviation 36.53 |
| Placebo | Latency to Persistent Sleep | -37.5 minutes | Standard Deviation 38.43 |
Other Pre-specified
Duration of Wake After Sleep Onset (WASO)
The secondary efficacy parameter is the duration of wake after sleep onset (WASO) measured by the PSG after 28 nights of the double blind treatment period. WASO was summarized at baseline and after 28 days double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. For each treatment group, the mean score at the end of the 28 nights was compared, adjusting for the baseline score. An ANCOVA model was used. Lower score indicates less waking time and thus considered improvement.
Time frame: 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neu-P11 20mg | Duration of Wake After Sleep Onset (WASO) | -28.1 minutes | Standard Deviation 42.04 |
| Neu-P11 50mg | Duration of Wake After Sleep Onset (WASO) | -36.1 minutes | Standard Deviation 64.12 |
| Placebo | Duration of Wake After Sleep Onset (WASO) | -13.3 minutes | Standard Deviation 46.23 |
Other Pre-specified
Number of Awakenings (NOA)
The secondary efficacy parameter is number of awakenings (NOA) measured by the PSG after 28 nights of the double blind treatment period. NOA was summarized at baseline and after 28 days double-blind treatment (actual and change from baseline) for each treatment group using descriptive statistics. For each treatment group, the mean score at the end of the 28 nights was compared, adjusting for the baseline score. An ANCOVA model was used. Lower score indicates less awakenings and thus considered improvement.
Time frame: 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neu-P11 20mg | Number of Awakenings (NOA) | -3.1 Awekenings | Standard Deviation 10.16 |
| Neu-P11 50mg | Number of Awakenings (NOA) | -0.1 Awekenings | Standard Deviation 10.28 |
| Placebo | Number of Awakenings (NOA) | 0.5 Awekenings | Standard Deviation 10.26 |