Autism Spectrum Disorder
Conditions
Brief summary
This is a randomized placebo controlled study in children diagnosed with autism spectrum disorder (ASD), to Investigate the Efficacy and Safety of Slenyto® to alleviate Sleep Disturbances in these children. . The main objective is to compare treatment effect of Slenyto® 2 mg or 5 mg to that of placebo on sleep duration (total sleep time \[TST\]) as assessed by the Sleep and Nap Diary after 3 weeks of double blind treatment.
Detailed description
This is a randomized placebo controlled study in children diagnosed with autism spectrum disorder (ASD). Children will have a documented history of this disorder, as confirmed or consistent with the International Classification of Diseases (ICD 10) or Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (Text Revision; DSM 5) criteria, having DSM-5 criteria based sleep disturbances at screening. The children will undergo 4 weeks of basic sleep hygiene and behavioral intervention, which will serve as a wash out period from any hypnotics and prohibited medications; Children with a documented history of sleep hygiene and behavioral intervention who are taking a prohibited medication will not require additional training and will undergo a 2-week wash out period before Visit 1. Children who are still found to be eligible for the study after the 4 week, basic sleep hygiene and behavioral intervention wash out period, will continue in a 2 week single blind (SB) placebo run in period. . After the 2 week SB placebo run in period (Visit 2; Week 2), children who are still found eligible for study participation will be randomized in a 1:1 ratio to receive either Slenyto® (1 or 5 mg prolonged release melatonin tablets) or placebo for 3 weeks double-blind treatment period. The starting dose will be 2X1mg Slenyto® or matching placebo. During these 3 weeks parents will complete the electronic sleep and nap diary every morning. After one week of double-blind treatment, on the last day of Week 3 ±3 days (Visit 3), sleep variables will be assessed to determine if dose modification (increase to 1X5 mg Slenyto® or matching placebo) is required. Children will then continue on 2 or 5 mg of Slenyto® or matching placebo to the end of the double blind period (End-of Study Visit 4; Week 5). Study duration will be either 5, 7, or 9 weeks, including the optional 2-weeks medication wash out and 4 weeks sleep hygiene and behavioral intervention periods (overlapping). The main objective is to compare treatment effect of Slenyto® 2 mg or 5 mg to that of placebo on sleep duration (total sleep time \[TST\]) as assessed by the Sleep and Nap Diary after 3 weeks of double blind treatment. The key secondary endpoints are SL and LSE. Safety will also be assessed by Adverse events, vital signs and physical examination.
Interventions
DRUGMelatonin
prolonged release 1 mg and 5 mg mini-tablets coated odorless and tasteless to facilitate swallowing
DRUGPlacebo
Placebo melatonin
Sponsors
Neurim Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* children 2 to 17.5 years of age at Visit 2 who comply with taking the study drug * Written informed consent provided by a legal guardian and assent (if needed) * A documented history of ASD according to or consistent with the ICD 10 or DSM 5 criteria, as confirmed by case note review showing that diagnosis was reached through assessment by a community pediatrician or pediatric neurologist or other health care professionals experienced in the diagnosis who took into account early developmental history and school records. * Current sleep problems consistent with DSM-5 criteria including: a minimum of 3 months of impaired sleep defined as ≤6 hours of continuous sleep AND ≥ 0.5-hour sleep latency from light off in 3 out of 5 nights based on parent reports and subject medical history. (The maintenance and latency problems do not necessarily have to be in the same 3 nights of the week.) * May be on a stable dose of non excluded medication for 3 months, including anti epileptics, anti depressants (selective serotonin reuptake inhibitor \[SSRIs\]), and β blockers. (Only morning administration of β blockers is allowed since β blockers at night have the potential to reduce endogenous * The sleep disturbance is not due to the direct physiological effects of any concomitant medications such as SSRIs, β blockers etc.
Exclusion criteria
* Have had treatment with any form of melatonin within 2 weeks prior to Visit * Have a known allergy to melatonin or lactose * Have a known moderate to severe sleep apnea * Have an untreated medical/ineffectively treated/psychological condition that may be the etiology of sleep disturbances * Are taking or have been taking prohibited medication within 2 weeks prior to Visit 1 * Are females of child bearing potential that are not using contraceptives and/or breastfeeding and that are sexually active (Abstinence is an acceptable method of contraception.) * Pregnant females * Are currently participating in a clinical trial or have participated in a clinical trial involving medicinal product within the last 3 months prior to the study * Participated in Study NEU\_CH\_7911 * Children with known renal or hepatic insufficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Sleep Time (TST) | after the 3 weeks (Week 5) of double blind treatment | the change from baseline in average TST time as assessed by a Sleep and Nap Diary |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Latency (SL) | after 3 weeks (Week 5) of double blind treatment | • Change from baseline in average SL as assessed by a Sleep and Nap Diary |
| Longest Sleep Episode (LSE) | after 3 weeks (Week 5) of double blind treatment | • Change from baseline in average LSE from the Sleep and Nap Diary . |
Outcome results
None listed