Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder.
Study Goal
To assess the efficacy and safety of prolonged-release melatonin minitablets (PedPRM) versus placebo for treating insomnia in children and adolescents with autism spectrum disorder (ASD) and neurogenetic disorders (NGD).
Results Summary
PedPRM significantly increased total sleep time by 57.5 minutes compared to 9.14 minutes with placebo and reduced sleep latency by 39.6 minutes versus 12.5 minutes with placebo. The treatment was generally safe, with somnolence being the most commonly reported adverse effect.
Population
Children and adolescents (2-17.5 years) with ASD (96.8%) or Smith-Magenis syndrome (3.2%) who had unimproved sleep despite behavioral interventions.
Effective Dosage
2 mg escalated to 5 mg.
Duration
13 weeks.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
novel pediatric-appropriate, prolonged-release melatonin minitablets (PedPRM) | increase | total sleep time (TST) | children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD) | 57.5 minutes | slept on average longer at night | #1 |
placebo | increase | total sleep time (TST) | children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD) | 9.14 minutes | slept on average longer at night | #2 |
PedPRM | decrease | sleep latency (SL) | children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD) | 39.6 minutes | decreased | #3 |
placebo | decrease | sleep latency (SL) | children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD) | 12.5 minutes | decreased | #4 |
PedPRM | increase | TST and/or SL | children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD) | 68.9% | rate of participants attaining clinically meaningful responses was significantly higher | #5 |
placebo | increase | TST and/or SL | children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD) | 39.3% | rate of participants attaining clinically meaningful responses | #6 |
PedPRM | decrease | overall sleep disturbance (CSDI) | children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD) | - | tended to decrease | #7 |
PedPRM | no change | safety | children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD) | - | was generally safe | #8 |
PedPRM | increase | somnolence | children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD) | - | was more commonly reported | #9 |
OBJECTIVE: To assess the efficacy and safety of novel pediatric-appropriate, prolonged-release melatonin minitablets (PedPRM) versus placebo for insomnia in children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD). METHOD: A total of 125 children and adolescents (2-17.5 years of age; 96.8% ASD, 3.2% Smith-Magenis syndrome [SMS]) whose sleep failed to improve on behavioral intervention alone were randomized (1:1 ratio), double-blind, to receive PedPRM (2 mg escalated to 5 mg) or placebo for 13 weeks. Sleep measures included the validated caregivers' Sleep and Nap Diary (SND) and Composite Sleep Disturbance Index (CSDI). The a priori primary endpoint was SND-reported total sleep time (TST) after 13 weeks of treatment. RESULTS: The study met the primary endpoint: after 13 weeks of double-blind treatment, participants slept on average 57.5 minutes longer at night with PedPRM compared to 9.14 minutes with placebo (adjusted mean treatment difference PedPRM-placebo -32.43 minutes; p = .034). Sleep latency (SL) decreased by 39.6 minutes on average with PedPRM and 12.5 minutes with placebo (adjusted mean treatment difference -25.30 minutes; p = .011) without causing earlier wakeup time. The rate of participants attaining clinically meaningful responses in TST and/or SL was significantly higher with PedPRM than with placebo (68.9% versus 39.3% respectively; p = .001) corresponding to a number needed to treat (NNT) of 3.38. Overall sleep disturbance (CSDI) tended to decrease. PedPRM was generally safe; somnolence was more commonly reported with PedPRM than placebo. CONCLUSION: PedPRM was efficacious and safe for treatment of insomnia in children and adolescents with ASD with/without ADHD and NGD. The acceptability of this pediatric formulation in a population who usually experience significant difficulties in swallowing was remarkably high. Clinical trial registration information-Efficacy and Safety of Circadin in the Treatment of Sleep Disturbances in Children With Neurodevelopment Disabilities; http://clinicaltrials.gov/; NCT01906866.