LONG-TERM EFFICACY AND SAFETY OF PEDIATRIC PROLONGED-RELEASE MELATONIN FOR INSOMNIA IN CHILDREN WITH AUTISM SPECTRUM DISORDER

Oral Session 1
Saturday, April 28, 2018 | 2:15pm-3:45pm | Room 342B

2:45pm-3:00pm
LONG-TERM EFFICACY AND SAFETY OF PEDIATRIC PROLONGED-RELEASE MELATONIN FOR INSOMNIA IN CHILDREN WITH AUTISM SPECTRUM DISORDER

Authors:
Carmen M. Schroder (France)*
Athanasios Maras (The Netherlands)
Beth A. Malow (USA)
Tali Nir (Israel)
Nava Zisapel (Israel)
Robert Findling (USA)
Paul Gringras (United Kingdom)

Introduction

A recent double-blind randomized placebo-controlled study demonstrated 3-months’ efficacy and safety of novel pediatric-appropriate prolonged-release melatonin minitablets (PedPRM; 2/5 mg) vs. placebo in children and adolescents with Autism Spectrum Disorders (ASD) and Neurogenetic Disorders (NGD) suffering from insomnia.
Objective: To investigate PedPRM (2,5,10 mg) long term efficacy and safety in patients receiving 1 year of PedPRM, as well as caregivers outcomes.

Materials and methods

A prospective 9-months open-label follow up study of efficacy and safety of PedPRM in community dwelling patients with ASD/NGD. Sleep measures included the validated caregivers’ Sleep and Nap Diary (SND) and Composite Sleep Disturbance Index (CSDI). Caregiver measures included Pittsburgh Sleep Quality Index (PSQI) Epworth Sleepiness Scale (ESS) and quality of life (WHO-5 well-being index).

Results

95 patients aged 2-17.5 years [mean age 9 + 4.24, 74.7% males] who completed the 3 months double-blind trial (51 from PedPRM arm and 44 from the placebo arm) at final 2/5mg dose received open-label PedPRM with optional dose adjustment to 2/5/10 mg/day after 3 months. By the end of the follow up period, 41 of the PedPRM randomized group completed 1 year of PedPRM and 38 of the placebo randomized group completed 9 months of PedPRM. The improvements in total sleep time (TST), sleep latency (SL) and duration of uninterrupted sleep (longest sleep episode) seen in the double blind-phase with PedPRM vs placebo were maintained throughout the follow up period. Subjects treated continuously with PedPRM for 52 weeks (N=41) slept on average 62.08 minutes longer (p=0.007), fell asleep -48.6minutes faster (p<0.001) and had longer uniterrupted sleep duration (89.1minutes; p=0.001). In addition, quality of sleep improved (p<0.001) and number of awakenings decreased > 50% (p=0.001). The placebo-randomised group (39 weeks; N=38) also improved following PedPRM treatment. There were no significant differences in PedPRM treatment effects between the randomization groups. In parallel, there were statistically significant and clinically relevant improvements in Child’s sleep disturbance and parents satisfaction of their child’s sleep patterns (CSDI), caregiver’s sleep quality (PSQI) (p<0.001 for all) and quality of life (WHO-5) (p=0.001) in all completers regardless of randomization history (N=79). PedPRM was generally safe; the most frequent treatment related adverse events were fatigue in 5.3% (5 events) and mood swings in 3.2% (3 events) of patients.

Conclusions

PedPRM is an effective and safe treatment option for long term (52 weeks) treatment of children with ASD suffering from insomnia and consequently improved caregivers well–being and quality of life.

Acknowledgements

Neurim Pharmaceuticals Ltd