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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Neurim Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:
NCT01903681
First received: July 16, 2013
Last updated: April 3, 2014
Last verified: June 2013
  Purpose

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.

Condition Intervention Phase
Sleep Problems
Drug: Circadin 2 mg
Drug: Circadin 10 mg
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Neurim Pharmaceuticals Ltd.:

Primary Outcome Measures:
  • baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    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.

  • adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 16
Study Start Date: March 2013
Study Completion Date: April 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Circadin 10 mg
Second arm higher dose
Drug: Circadin 10 mg
Second arm higher dose
Active Comparator: Circadin 2 mg
First arm lower dose
Drug: Circadin 2 mg
First arm lower dose
Other Name: non

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01903681

Locations
Netherlands
Centre for Human Drug Research
Leiden, Netherlands, 2333
Sponsors and Collaborators
Neurim Pharmaceuticals Ltd.
  More Information

No publications provided

Responsible Party: Neurim Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT01903681     History of Changes
Other Study ID Numbers: CHDR1219
Study First Received: July 16, 2013
Last Updated: April 3, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Neurim Pharmaceuticals Ltd.:
Sleep problems, autism spectrum disorder, prolonged-release melatonin, Circadin, endogenous saliva melatonin
Smith-Magenis syndrome, Angelman syndrome, Tuberous Sclerosis

Additional relevant MeSH terms:
Sleep Disorders
Dyssomnias
Parasomnias
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Mental Disorders
Melatonin
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on July 24, 2014