SLEEP DISTURBANCES IN CHILDREN WITH NEURODEVELOPMENTAL DISABILITIES MedDRA version: 18.0 Level: LLT Classification code 10040997 Term: Sleep disturbances System Organ Class: 100000004873
Conditions
Interventions
Trade Name: Circadin
Product Name: Circadin
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Melatonin
CAS Number: 73-
Sponsors
Neurim Pharmaceuticals (1991) Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for study entry, all patients must satisfy all of the following criteria at screening. 1. Must be children 2 to 17.5 years of age at Visit 2 who comply with taking the study drug. 2. Must have written informed consent provided by a legal guardian and assent (if needed). 3. Must have a documented history of ASD according to ICD-10 or DSM-5/4 or neurodevelopmental disabilities caused by neurogenetic diseases (Smith-Magenis syndrome [SMS], Angelman syndrome, Bourneville’s disease [tuberous sclerosis]) as confirmed by case note review showing that diagnosis was reached through assessment by a community paediatrician or paediatric neurologist or other health care professionals experienced in the diagnosis, who took into account early developmental history and school records. 4. Must have current sleep problems including: A minimum of 3 months of impaired sleep defined as =6 hours of continuous sleep and/or = 0.5 hour sleep latency from light off in 3 out of 5 nights based on parent reports and patient medical history. (The maintenance and latency problems do not necessarily have to be in the same 3 nights of the week.) 5. May be on a stable dose of non-excluded medication for 3 months, including anti-epileptics, anti-depressants (SSRIs), stimulants, all mood changing drugs and beta blockers. 6. The sleep disturbance is not due to the direct physiological effects of the medication (SSRIs, stimulants, etc.). At the end of 4 weeks of sleep hygiene training (for those who need it) and 2 weeks of run-in, children will be eligible to continue the study if they comply with the following: 1. Continue to fulfil sleep problem criteria (see Inclusion Criterion 4). 2. Parents demonstrate compliance in Sleep and Nap Diary completion (5 out of 7 nights). 3. Continue to fulfil all other eligibility criteria. Are the trial subjects under 18? yes Number of subjects for this age range: 120 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Have had treatment with any form of melatonin within 2 weeks prior to Visit 1. 2. Have a known allergy to melatonin or lactose. 3. Have a known moderate to severe sleep apnea. 4. Have untreated medical/ineffectively treated/psychological condition that may be the etiology of sleep disturbances. 5. Did not respond to previous Circadin therapy based on past medical history records in the last 2 years. 6. Are taking or have been taking prohibited medication within 2 weeks prior to Visit 1. 7. Are females of child bearing potential that are not using contraceptives and/or are breastfeeding and that are sexually active (Abstinence is an acceptable method of contraception). 8. Pregnant females 9. Are currently participating in a clinical trial or have participated in a clinical trial involving medicinal product within the last 3 months prior to the study (this does not include patients who participated in the Phase I PK study who can be already included in the study) . 10. Children with known renal or hepatic insufficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the treatment effect of Circadin 2/5 mg to that of placebo on sleep maintenance (total sleep time [TST]) as assessed by the Sleep and Nap Diary after 13 weeks of double-blind treatment.;Primary end point(s): Total sleep time as assessed by a Sleep and Nap Diary ;Timepoint(s) of evaluation of this end point: after the 13- week double-blind treatment period; Secondary Objective: To compare treatment effect of Circadin 2/5mg to placebo on - sleep latency, duration of wake after sleep onset period, number of awakenings and duration of the longest sleep period as derived from a Sleep and Nap Diary after 13 weeks double-blind treatment. - children’s social functioning at home, in school, and community settings as assessed by the CGAS after 13 weeks double-blind treatment. - children’s behavior at home and in school as assessed by the SDQ after 13 weeks double-blind treatment. - sleep parameters as measured by actigraphy after 13 weeks double-blind treatment. To compare safety and tolerability of Circadin to placebo and evaluate safety and tolerability throughout the study incl. runout period using AE eliciting method TESS Questionnaire. To assess vital signs and physical examination in Circadin and placebo groups. To compare the number of dropouts between Circadin 2/5 mg and placebo during 13 weeks double-blind treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints • Sleep latency as assessed by a Sleep and Nap Diary • Duration of wake after sleep onset from the Sleep and Nap Diary • Number of awakenings from the Sleep and Nap Diary • Longest sleep period from the Sleep and Nap Diary • Social functioning at home, in school, and in community settings as assessed by the CGAS • Behavior at home and in school as assessed by the SDQ • Number of dropouts • Assessment of sleep parameters by actigraphy Secondary Safety Endpoints • Adverse events using the TESS Questionnaire. • Vital signs • Physical examination ; Timepoint(s) of evaluation of this end point: Secondary Efficacy Endpoints: after 13 weeks of double-blind treatment. Secondary Safety Endpoints: - AEs: throughout the study and upon study withdrawal - Vital signs and physical exam: at each visit including the run-out period. | — |
Countries
Finland, France, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Trial Management
Neurim Pharmaceuticals (1991) Ltd.
Outcome results
None listed