Efficacy and Safety of Circadin® in the Treatment of Sleep Disturbances in Children With Neurodevelopment Disabilities

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Neurim Pharmaceuticals Ltd.
Sponsor:
Information provided by (Responsible Party):
Neurim Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:
NCT01906866
First received: July 11, 2013
Last updated: December 27, 2015
Last verified: October 2015
  Purpose
The purpose of this study is to establish the efficacy and safety of Circadin in children with neurodevelopmental disorders and to determine the dose, this randomized, placebo-controlled study is planned to evaluate the efficacy of a double-blind, 13 week treatment period with Circadin 2/5mg in improving maintenance of sleep, sleep latency and additional parameters in children with neurodevelopmental disabilities. The efficacy and safety of Circadin 2/5 mg will continue to be assessed during an open-label extension period of 13 weeks.

Condition Intervention Phase
Sleep Disorders
Drug: Circadin 2/5/10 mg
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled Study to Investigate the Efficacy and Safety of Circadin® to Alleviate Sleep Disturbances in Children With Neurodevelopmental Disabilities

Resource links provided by NLM:


Further study details as provided by Neurim Pharmaceuticals Ltd.:

Primary Outcome Measures:
  • The total sleep time will be measured for the Circadin 2/5 mg and placebo by a Sleep and nap diary questionnaire after the 13 week, double-blind treatment period. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire


Secondary Outcome Measures:
  • Sleep latency will be measured for the Circadin 2/5 mg and placebo by a Sleep and Nap Diary after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    questionnaire

  • The duration of wake after sleep onset period will be measured for the Circadin 2/5 mg and placebo by a Sleep and Nap Diary after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire

  • The number of awakenings during the night will be measured for the Circadin 2/5 mg and placebo by a Sleep and Nap Diary after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire

  • The duration of the longest sleep period will be measured for the Circadin 2/5 mg and placebo by a Sleep and Nap Diary after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 Years ] [ Designated as safety issue: No ]
    Questionnaire

  • The children's social functioning at home, in school, and community settings will be measured for the Circadin 2/5 mg and placebo by the Children Global Assessment Scale (CGAS) Questionnaire after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire

  • The children's behavior at home, in school, and community will be measured for the Circadin 2/5 mg and placebo by the Strength of Difficulties Questionnaire (SDQ) Questionnaire filled out by the parents after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire

  • The number of dropouts between Circadin 2/5 mg to that of placebo will be compared during the 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
  • Sleep parameters (rest/activity cycles) will be measured for the Circadin 2/5 mg and placebo as measured by actigraphy after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    The Actigraph will be worn on the wrist at night and collect the Sleep parameters

  • Safety and tolerability throughout the study will be measured for the Circadin 2/5 mg and placebo throughout the study using AE eliciting method Treatment Emergent Signs and Symptoms (TESS) [ Time Frame: up to 2.5 years ] [ Designated as safety issue: Yes ]
    Questionnaire

  • The following Vital Signs will be measured: blood pressure, pulse, breathing and body temperature. They will be compared between the Circadin and placebo groups. [ Time Frame: up to 2.5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: October 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Circadin 2/5/10 mg Drug: Circadin 2/5/10 mg
Active arm
Placebo Comparator: Placebo
Placebo arm
Drug: Placebo

  Eligibility

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

Inclusion Criteria:

  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 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, 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 with more than 0.5 hour sleep latency from light off in 3 out of 5 nights.
  5. Must 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 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.

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 disallowed medication within 2 weeks prior to Visit 1.
  7. Are females of child bearing potential that are not using contraceptives.
  8. 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.

  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: NCT01906866

Contacts
Contact: Neurim Pharmaceutical (1991) Ltd. +972-3-6499340 neurim@neurim.com

  Show 28 Study Locations
Sponsors and Collaborators
Neurim Pharmaceuticals Ltd.
Investigators
Principal Investigator: Paul Gringras, PhD Thoma`s Hospital, Westminster Bridge Rd, London
Principal Investigator: Robert Findling, MD Kennedy Krieger Institute, Baltimore, Maryland, USA
  More Information

Responsible Party: Neurim Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT01906866     History of Changes
Other Study ID Numbers: NEU_CH_7911 
Study First Received: July 11, 2013
Last Updated: December 27, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Neurim Pharmaceuticals Ltd.:
Sleep disturbance
Circadian
Prolong release melatonin
Autism Spectrum Disorder
Smith-Magenis Syndrome
Angelman Syndrome
tuberous sclerosis

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

ClinicalTrials.gov processed this record on April 27, 2016