A Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of Circadin® To Alleviate Sleep Disturbances in Children with Neurodevelopment Disabilities.
- Conditions
- Sleep disordersSleep problems10040998
- Registration Number
- NL-OMON41494
- Lead Sponsor
- eurim Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
1.1. 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 or consistent with the ICD 10 or DSM 5/4 criteria, or neurodevelopmental disabilities caused by neurogenetic diseases (i.e., Smith Magenis syndrome, Angelman syndrome, Bourneville*s disease [tuberous sclerosis]) as confirmed by case note review showing that diagnosis was reached through assessment by a community pediatrician or pediatric 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 (selective serotonin reuptake inhibitor [SSRIs]), stimulants, all mood changing drugs and * blockers. (Only morning administration of * blockers is allowed since * blockers at night have the potential to reduce endogenous melatonin levels and might cause disturbed sleep)
6. The sleep disturbance is not due to the direct physiological effects of any concomitant medications such as SSRIs, stimulants, etc.
After completing 4 weeks of sleep hygiene training and 2 weeks of placebo run in, patients will be eligible to continue the study if they comply with the following:
* Continue to fulfill sleep problem criteria (see Inclusion Criterion 4) based on the completed Sleep and Nap Diary entered into the electronic case report form
* Parents demonstrate compliance in Sleep and Nap Diary completion (5 out of 7 nights). Compliance means that in at least 5 out of 7 nights per week (total of 2 weeks before each scheduled visit) the parents complete the diary pages with all mandatory questions (mandatory questions are marked with an asterisk [*] in Appendix 1).
* Continue to fulfil all other eligibility 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 an 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 disallowed medication within 2 weeks prior to Visit 1 (Section 7.1)
7. Are females of child bearing potential that are not using contraceptives and/or 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy parameter is TST time as assessed by a Sleep and Nap Diary<br /><br>after the 13-week, double-blind treatment period.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Sleep latency as assessed by a Sleep and Nap Diary after 13 weeks (Week 15)<br /><br>of double blind treatment<br /><br>* Duration of wake after sleep onset from the Sleep and Nap Diary after 13<br /><br>weeks (Week 15) of double blind treatment<br /><br>* Number of awakenings from the Sleep and Nap Diary after 13 weeks (Week 15) of<br /><br>double blind treatment<br /><br>* Longest sleep period from the Sleep and Nap Diary after 13 weeks (Week 15) of<br /><br>double blind treatment<br /><br>* Social functioning at home, in school, and in community settings as assessed<br /><br>by the CGAS after 13 weeks (Week 15) of double<br /><br>blind treatment<br /><br>* Behavior at home and in school as assessed by the SDQ after 13 weeks (Week<br /><br>15) of double blind treatment<br /><br>* Number of dropouts during the 13 week (Week 15) double blind treatment period<br /><br>* Assessment of sleep parameters by actigraphy after 13 weeks (Week 15) of<br /><br>double blind treatment</p><br>