Efficacy and Safety of Slenyto for Insomnia in Children With ASD (ASD)

A Randomized, Placebo Controlled Study to Investigate the Efficacy and Safety of Slenyto® to Alleviate Sleep Disturbances in Children With Autism Spectrum Disorder

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.

Study Overview

• Status: Withdrawn
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Melatonin; Drug: Placebo

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.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melatonin; Slenyto® 1 mg / 5 mg prolonged release Melatonin tablets (pink and yellow) film coated 3 mm in diameter,	Drug: Melatonin; prolonged release 1 mg and 5 mg mini-tablets coated odorless and tasteless to facilitate swallowing; Other Names: Slenyto
Placebo Comparator: Placebo melatonin; Placebo melatonin will be identical in appearance (pink and yellow) and formulation to active Slenyto® tablets, but will contain no active melatonin.	Drug: Placebo; Placebo melatonin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Sleep Time (TST)	the change from baseline in average TST time as assessed by a Sleep and Nap Diary	after the 3 weeks (Week 5) of double blind treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Latency (SL)	• Change from baseline in average SL as assessed by a Sleep and Nap Diary	after 3 weeks (Week 5) of double blind treatment
Longest Sleep Episode (LSE)	• Change from baseline in average LSE from the Sleep and Nap Diary .	after 3 weeks (Week 5) of double blind treatment

Collaborators and Investigators

• Sponsor: Neurim Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 15, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: NEU_CH_7913

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No