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

Sleep Problems Clinical Trial

Official title:

Open Label, Single Ascending Dose, Cross-over Study to Assess the Pharmacokinetics of Circadin® (Prolonged-Release Melatonin) Mini Tablets in Children With Neurodevelopmental Disorders and Sleep Disturbances

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01903681
• Other study ID #: CHDR1219
• Status: Completed
• Phase: Phase 1
• First received: July 16, 2013
• Last updated: April 3, 2014
• Start date: March 2013
• Est. completion date: April 2014

Study information

• Verified date: June 2013
• Source: Neurim Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 17 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

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;

Participation in an investigational drug study within 90 days prior to the first dose and/or participation in more than 4 clinical trials in the last year. -

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Dyssomnias
• Mental Disorders Diagnosed in Childhood
• Parasomnias
• Sleep Disorders
• Sleep Problems

Intervention

Drug:
• Circadin 2 mg
First arm lower dose
• Circadin 10 mg
Second arm higher dose

Locations

Country	Name	City	State
Netherlands	Centre for Human Drug Research	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Neurim Pharmaceuticals Ltd.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	Yes