Gringras P, et al. - The authors undertook this study to evaluate the efficacy and safety of novel pediatric-appropriate prolonged-release melatonin minitablets (PedPRM) vs. placebo for insomnia in children with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD). For treatment of insomnia, PedPRM was efficacious and safe in children with ASD with/without ADHD and NGD. The acceptability of this pediatric formulation was remarkably high in a population who usually experienced significant difficulties in swallowing.

• During this study, double-blind randomisation was done on 125 children (2-17.5 years; 96.8% ASD, 3.2% Smith-Magenis syndrome [SMS]) whose sleep failed to improve on behavioral intervention alone (1:1 ratio), to receive PedPRM (2mg escalated to 5mg) or placebo for 13 weeks.
• The validated caregivers’ Sleep and Nap Diary (SND) and Composite Sleep Disturbance Index (CSDI) were included as sleep measures.
• SND-reported total sleep time (TST) after 13 weeks of treatment was a priori primary endpoint.

• The study met the primary endpoint: participants slept on average 57.5 minutes longer at night with PedPRM compared to 9.14 with placebo (adjusted mean treatment difference PedPRM–placebo -32.43 minutes; p=.034) after 13 weeks of double-blind treatment.
• With PedPRM, sleep latency (SL) decreased by 39.6 minutes on average and 12.5 with placebo (adjusted mean treatment difference -25.30 minutes; p=.011) without causing earlier wakeup time.
• Compared to placebo, rate of participants attaining clinically meaningful responses in TST and/or SL was significantly higher with PedPRM (68.9% vs 39.3% respectively; p=.001) corresponding to number needed to treat (NNT) 3.38.
• Overall sleep disturbance (CSDI) tended to decrease.
• As per the outcomes, PedPRM was generally safe.
• Compared to placebo, somnolence was more commonly reported with PedPRM.