efficacy and safety of slenyto for insomnia in children with asd

Conditions: Autism Spectrum Disorder

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.

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.

Eligibility criteria:
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