Sleep ProblemsPhase 1NCT01903681
Assessment of the Pharmacokinetics of Circadin® in Children With Neurodevelopmental Disorders and Sleep Disturbances
A Phase 1 study testing Circadin 2 mg and Circadin 10 mg in people with Sleep Problems, run by Neurim Pharmaceuticals Ltd. at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Sleep Problems
- What is being tested?
- Circadin 2 mg and Circadin 10 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2013to Apr 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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. -
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- Circadin 2 mg, Circadin 10 mg
- Keywords
- Sleep problems, autism spectrum disorder, prolonged-release melatonin, Circadin, endogenous saliva melatonin, Smith-Magenis syndrome, Angelman syndrome, Tuberous Sclerosis
- Medical subject headings
- Parasomnias, Autism Spectrum Disorder, Smith-Magenis Syndrome, Angelman Syndrome, Tuberous Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Circadin 2 mgDrug
Also called non
First arm lower dose
Circadin 10 mgDrug
Second arm higher dose
| Study group | Role | What they receive |
|---|---|---|
| Circadin 10 mg | Active comparator | Second arm higher dose Receives: Drug: Circadin 10 mg |
| Circadin 2 mg | Active comparator | First arm lower dose Receives: Drug: Circadin 2 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2013 (estimated)
- Study startMar 2013
- Primary completionFeb 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep ProblemsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurim Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01903681
- Sponsor's protocol ID
- CHDR1219
- Status last verified
- Jun 2013
- First submitted
- 16 Jul 2013
- Last updated
- 4 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01903681
- Acronym / sponsor ID
- CHDR1219
- Conditions
- Sleep Problems
- Keywords
- Sleep problems, autism spectrum disorder, prolonged-release melatonin, Circadin, endogenous saliva melatonin, Smith-Magenis syndrome, Angelman syndrome, Tuberous Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Neurim Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- Mar 2013
- Primary completion
- Feb 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 19 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Circadin 10 mg | Active comparator | Drug: Circadin 10 mgSecond arm higher dose |
| Circadin 2 mg | Active comparator | Drug: Circadin 2 mgFirst arm lower dose |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Circadin 2 mgAlso: nonFirst arm lower dose | Drug | Circadin 2 mg |
| Circadin 10 mgSecond arm higher dose | Drug | Circadin 10 mg |
Primary outcome
baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion
Time frame: up to 1 year
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
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
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Circadin 2 mg and Circadin 10 mg in people with Sleep Problems, run by Neurim Pharmaceuticals Ltd. at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion (time frame: up to 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2014.