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

Primary Purpose

Sleep Problems

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

Circadin 2 mg

Circadin 10 mg

About this trial

This is an interventional basic science trial for Sleep Problems focused on measuring Sleep problems, autism spectrum disorder, prolonged-release melatonin, Circadin, endogenous saliva melatonin, Smith-Magenis syndrome, Angelman syndrome, Tuberous Sclerosis

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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. -

Sites / Locations

Centre for Human Drug Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Circadin 10 mg

Circadin 2 mg

Arm Description

Second arm higher dose

First arm lower dose

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01903681

First Posted

July 16, 2013

Last Updated

April 3, 2014

Sponsor

Neurim Pharmaceuticals Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT01903681

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2013

Overall Recruitment Status

Completed

Study Start Date

March 2013 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Neurim Pharmaceuticals Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sleep Problems

Keywords

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Circadin 10 mg

Arm Type

Active Comparator

Arm Description

Second arm higher dose

Arm Title

Circadin 2 mg

Arm Type

Active Comparator

Arm Description

First arm lower dose

Intervention Type

Drug

Intervention Name(s)

Circadin 2 mg

Other Intervention Name(s)

non

Intervention Description

First arm lower dose

Intervention Type

Drug

Intervention Name(s)

Circadin 10 mg

Intervention Description

Second arm higher dose

Primary Outcome Measure Information:

Title

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

Description

Time Frame

up to 1 year

Title

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

Description

Time Frame

up to 1 year

Title

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

Description

Time Frame

up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility 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. -

Facility Information:

Facility Name

Centre for Human Drug Research

City

Leiden

ZIP/Postal Code

2333

Country

Netherlands

12. IPD Sharing Statement

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

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