Assessment of the Pharmacokinetics of Circadin® in Children With Neurodevelopmental Disorders and Sleep Disturbances

NCT01903681 | Completed Phase 1 DMC

• 1 other identifier: CHDR1219
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

There is increasing evidence that chronic sleep disorders in children with autism spectrum disorder (ASD), Angelman Syndrome (AS) and Smith-Magenis syndrome (SMS) are associated with disturbed melatonin secretion and melatonin administration has been shown to be effective in these populations. For children who have difficulties swallowing a tablet, Neurim has developed an age-appropriate Melatonin formulation in the form of mini-tablets which have the same dissolution profile as the Circadin® tablets product, thus should produce the same melatonin concentration-time profile with the same effects. This study concerns the pharmacokinetic study. The purpose of this study is to :

• Establish the 24 hour baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
• Establish the concentration-time profile of saliva melatonin concentrations and 24 hour 6-SMT urine excretion after 2 and 10 mg Circadin® mini-tablets single dose administration in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
• Evaluate the adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.

Conditions

Sleep Problems

Keywords

Sleep problems, autism spectrum disorder, prolonged-release melatonin, Circadin, endogenous saliva melatonin; Smith-Magenis syndrome, Angelman syndrome, Tuberous Sclerosis

Outcome Measures

Primary Outcomes (3)

• baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion

  To establish the 24 hour baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.

  up to 1 year

• concentration-time profile of saliva melatonin concentrations and 24 hour 6-SMT urine excretion after 2 and 10 mg Circadin® mini-tablets single dose administration

  To establish the concentration-time profile of saliva melatonin concentrations and 24 hour 6-SMT urine excretion after 2 and 10 mg Circadin® mini-tablets single dose administration in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.

  up to 1 year

• adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets

  To evaluate the adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.

  up to 1 year

Study Arms (2)

Circadin 10 mg

ACTIVE COMPARATOR

Second arm higher dose

Drug: Circadin 10 mg

Circadin 2 mg

ACTIVE COMPARATOR

First arm lower dose

Drug: Circadin 2 mg

Interventions

Circadin 2 mg DRUG

First arm lower dose

Also known as: non

Circadin 2 mg

Circadin 10 mg DRUG

Second arm higher dose

Circadin 10 mg

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject must be 2 to 17 years old
• Subject has a documented history of autistic spectrum disorder (ASD; as confirmed according to, DSM-IV-TR 299.00, 299.10 and 299.80 or ICD 10: F 84.0, F84.2, F84.3, F84.5, F84.9 ) or one of the following neurogenetic diseases according to ICD 10: Smith-Magenis syndrome, Angelman syndrome or Tuberous Sclerosis (Bourneville's disease)
• Subject has current sleep problems; defined as difficulty initiating or maintaining sleep, or non restorative sleep, for at least 1 month (DSM-IV 307.42). Subject is able to comply with taking the study drug and collaborate freely with the study procedures;
• Written informed consent from parents having parental responsibility or from the legal guardian(s). In the case of a child is aged 12 years or older the written informed consent of the child is needed in addition to that of parents having responsibility/legal guardian;
• Subject is able to understand instructions in Dutch.

You may not qualify if:

• Subject has history of difficulty with swallowing and/or easy choking;
• Subject has current symptoms suggestive of obstructive sleep apnea syndrome or any breathing related sleep disorders or periodic limb movements;
• Subject has known clinically significant disturbance(s) in hepatic and/or renal function;
• Subject has non-stable epileptic attacks within 3 months prior to screening, in case of a history of epilepsy;
• Subject who currently has asthmatic symptoms;
• Subject has untreated medical/psychological condition that may be the etiology of sleep disturbances;
• Subject is unable to refrain from the use of disallowed concomitant medication ordietary supplements (see paragraph 3.4) from 1 week prior to study occasions;
• Subject is unable to refrain from caffeine-containing products for 24 hours before each occasion;
• Subject has a known allergy to melatonin;
• Female subject who is pregnant at time of screening;
• Subject has unstable use of allowed medication within 2 months prior to the screening;
• Subject has clinically relevant periodontal disease and/or oral injuries as judged by the investigator;
• Subject is unable to refrain from eating bananas and chocolate during the entire day before saliva collection;
• Subject is unable to refrain from drinks containing artificial colorants, caffeine (including but not limited to coffee, tea, cola), or alcohol during the day of the collection;
• Subject is unable to refrain from aspirin or drugs that contain ibuprofen on the collection day;

Sponsors & Collaborators

• Neurim Pharmaceuticals Ltd.: lead

Study Sites (1)

Centre for Human Drug Research

Leiden, 2333, Netherlands

Location

MeSH Terms

Conditions

Parasomnias; Autism Spectrum Disorder; Smith-Magenis Syndrome; Angelman Syndrome; Tuberous Sclerosis

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Chronobiology Disorders; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Movement Disorders; Central Nervous System Diseases; Imprinting Disorders; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2013
• First Posted: July 19, 2013
• Study Start: March 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 4, 2014

Record last verified: 2013-06

Locations

NL (1)