Long Term Safety Study of Study Drug (Eszopiclone) in Children and Adolescents With ADHD -Associated Insomnia

A Long Term, Open-Label, Safety Study of Eszopiclone in Children (6 to 11 Years) and Adolescents (12 to 17 Years) With Attention Deficit/Hyperactivity Disorder Associated Insomnia

A multicenter study to evaluate the safety of eszopiclone in children (6 11 years of age, inclusive) and adolescents (12 17 years of age, inclusive) with attention deficit/hyperactivity disorder (ADHD) associated insomnia.

Study Overview

• Status: Completed
• Conditions: Insomnia; Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: eszopiclone; Drug: eszopiclone

Detailed Description

This is a multi center, open label, long term safety study in pediatric subjects 6 through 17 years of age, inclusive, with a diagnosis of ADHD associated insomnia. Subjects who complete Study 190 246 (Rollover subjects) and meet the study enrollment criteria will be allowed to participate in this long term safety study. Additionally, Treatment naïve subjects will be enrolled in this long term safety study in order to meet the overall subject enrollment objective of obtaining 100 subjects with 12 months of treatment. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.

• Study Type: Interventional
• Enrollment (Actual): 304
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • REM Medical Clinical Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Study Centers, LLC
  • California
    • Carson, California, United States, 90746
      • AV Institute, Inc.
    • Costa Mesa, California, United States, 92626
      • Clinical Innovations, Inc.
    • Glendale, California, United States, 91204
      • Behavioral Research Specialists, LLC
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • Oceanside, California, United States, 92056
      • North County Clinical Research (NCCR)
    • Orange, California, United States, 92868
      • Pacific Clinical Research Medical Group
    • Orange, California, United States, 92868
      • SDS Clinical Trials, Inc.
    • Riverside, California, United States, 92506
      • Clinical Innovations, Inc.
    • San Diego, California, United States, 92123
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92128
      • Clinical Innovations
    • Santa Ana, California, United States, 92701
      • Neuropsychiatric Research Center of Orange County
    • Santa Ana, California, United States, 92705
      • Apex Research Institute
    • Santa Ana, California, United States, 92705
      • Clinical Innovations, Inc.
    • Wildomar, California, United States, 92595
      • Elite Clinical Trials, Inc.
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves, Inc.
  • Florida
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hallandale Beach, Florida, United States, 3309
      • MD Clinical
    • Hialeah, Florida, United States, 33013
      • Amedica Research Institute, Inc.
    • Lauderhill, Florida, United States, 33319
      • Behavioral Clinical Research Inc.
    • Lauderhill, Florida, United States, 33319
      • Behavioral Clinical Research, Inc.
    • Loxahatchee Groves, Florida, United States, 33470
      • Pediatric Neurology and Epilepsy Center
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center, LLC
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research Inc.
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • Orlando, Florida, United States, 32822
      • Florida Institute for Clinical Research, LLC
    • Pinellas Park, Florida, United States, 33782
      • DMI Research Inc.
    • Spring Hill, Florida, United States, 34609
      • Florida Sleep Institute
    • Tampa, Florida, United States, 33607
      • SomnoMedics, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Sleep Disorders Center of Georgia
    • Roswell, Georgia, United States, 30076
      • Northwest Behavioral Research Center
  • Idaho
    • Eagle, Idaho, United States, 83616
      • Mountain West Clinical Trials
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Suburban Lung Associates, SC
    • Libertyville, Illinois, United States, 601048
      • Capstone Clinical Research
    • Naperville, Illinois, United States, 60563
      • AMR Baber Research, Inc.
    • Vernon Hills, Illinois, United States, 60061
      • Sleep and Behavior Medicine Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Davis Clinic
    • Indianapolis, Indiana, United States, 46260
      • Goldpoint Clinical Research, LLC
    • New Albany, Indiana, United States, 47150
      • Nassim, McMonigle, Mescia & Associates
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Psychiatric Associates
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Brownsboro Park Pediatrics
    • Owensboro, Kentucky, United States, 42301
      • Pedia Research, LLC
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Lake Charles Clinical Trials
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates, Inc.
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • MD
  • Massachusetts
    • Haverhill, Massachusetts, United States, 01830
      • ActivMed Practices and Research
    • Newton, Massachusetts, United States, 02459
      • Neurocare, Inc.
    • North Andover, Massachusetts, United States, 01845
      • ActivMed Practices and Research
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • Neurobehavioral Medicine Group
    • Sterling Heights, Michigan, United States, 48314
      • Clinical Nuerophysiology Services, PC
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Premier Psychicatric Research Institute, LLC
    • Lincoln, Nebraska, United States, 68516
      • Midwest Children's Health Research Institute
  • Nevada
    • Henderson, Nevada, United States, 89015
      • Clinical Research Center Of Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry and Behavioral Medicine, Inc.
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes, LLC
    • Willingboro, New Jersey, United States, 08046
      • CRI Worldwide, LLC
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • NorthCoast Clinical Trials, Inc.
    • Canton, Ohio, United States, 44718
      • Neuro-Behavioral Clnical Research
    • Middleburg Heights, Ohio, United States, 44130
      • Cleveland Sleep Research Center
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research, LLC
  • Oklahoma
    • Enid, Oklahoma, United States, 72703
      • Cutting Edge Research of Enid
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
    • Oklahoma City, Oklahoma, United States, 73116
      • Cutting Edge Research Group
    • Oklahoma City, Oklahoma, United States, 73112
      • Pahl Pharmaceutical Professionals, LLC
    • Oklahoma City, Oklahoma, United States, 73112
      • SP Research
    • Oklahoma City, Oklahoma, United States, 73139
      • Eminence Research LLC
    • Tulsa, Oklahoma, United States, 74103
      • Paradigm Research Professonals, LLP
    • Tulsa, Oklahoma, United States, 74104
      • Tulsa Clinical Research
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Cyn3rgy Research
    • Portland, Oregon, United States, 97210
      • Oregon Center for Clinical Investigations, Inc.
    • Salem, Oregon, United States, 97301
      • Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Texas
    • Arlington, Texas, United States, 76011
      • Academy of Clinical Research
    • Dallas, Texas, United States, 75243
      • Pillar Clinical Research, LLC
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
    • Houston, Texas, United States, 77008
      • Claghorn-Lesem Research Clinic, Ltd.
    • Houston, Texas, United States, 77024
      • Allegiant Clinical Research
    • Houston, Texas, United States, 77042
      • MD
    • Plano, Texas, United States, 75024
      • The Mech Center
    • San Antonio, Texas, United States, 78258
      • Road Runner Research
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research, LLC
  • Virginia
    • Richmond, Virginia, United States, 23230
      • Alliance Research Group
    • Virginia Beach, Virginia, United States, 23452
      • Brighton Research Group, LLC
  • Washington
    • Kirkland, Washington, United States, 98033
      • Eastside Therapeutic Resource

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Inclusion Criteria:

• Subject is male or female 6 17 years of age, inclusive, at the time of consent.
• Subject must have a diagnosis of ADHD as defined by DSM-IV criteria • The diagnosis for Rollover subjects will be taken from the Screening visit of Study 190 246. Treatment naïve subjects will have these assessments performed at the Screening visit.
• Subject must have documented ADHD associated insomnia, defined as the subject or subject's parent/legal guardian having reported repeated difficulty with sleep initiation (sleep latency >30 minutes) or consolidation (wake time after sleep onset > 45 minutes),>despite adequate age appropriate time and opportunity for sleep.
• Subject has either >30 minutes latency to persistent sleep (LPS) or >45 minutes wake time after sleep onset (WASO) demonstrated by PSG.
• Subject or subject's parent/legal guardian should have reported daytime functional impairment as a result of sleep problems.
• Subject or subject's parent/legal guardian should have reported attempted and failed behavioral interventions for sleep problems, including a regular bedtime and rise time.
• Subject's sleep disturbance must not be attributable to either the direct physiologic effect of a drug of abuse or misuse of a prescribed medication whether it is being used as intended or in an illicit manner.
• Female subjects ≥8 years of age must have a negative serum pregnancy test at screening
• Subject must be in good general health.
• Subject must be able to swallow tablets.
• If subjects are currently taking medication for ADHD, they must be on a stable dose and regimen for at least one month, and preferably for at least 3 months prior to the time of consent

Exclusion Criteria:

• Subject with weight <10th percentile for age and gender
• Subject has any clinically significant or unstable medical abnormality/illness
• Subject has a documented history of Bipolar I or II Disorder, major depression, conduct disorder, generalized anxiety disorder (other than obsessive-compulsive disorder) or any history of psychosis, as determined by medical or psychiatric history or as determined by clinical interview using the MINI-Kid at Visit 1.
• Subject has periodic limb movement >5 times per hour, as demonstrated on PSG.
• Subject has sleep disordered breathing, as demonstrated on PSG.
• Subject has another primary sleep disorder (or secondary sleep disorder that is causing clinical impairment or any other known or suspected medical or psychiatric condition that has affected or may affect sleep
• Subject has a history of circadian rhythm disorder or will travel across ≥3 time zones more than once during the study.
• Subject has organic brain disease, or a history of febrile seizures.
• Subject is, in the opinion of the investigator, at suicidal or homicidal risk.
• Female subject who is pregnant, lactating or planning to become pregnant.
• Subject is taking any psychotropic or disallowed medications,
• Subject has a history of severe allergies to more than 1 class of medications or multiple adverse drug reactions.
• Subject has a history of allergic reaction or has a known or suspected sensitivity to racemic zopiclone, eszopiclone, or any substance that is contained in the formulation.
• Subject has a history of alcohol or substance abuse within 3 months of study participation
• Subject has participated in any investigational study within 30 days prior to study entry or is currently participating in another clinical trial, except Study 190 246.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2mg eszopiclone (6-11yrs), 3mg eszopiclone (12-17yrs)	Drug: eszopiclone; One 2 mg tablet per day for 12 months; Drug: eszopiclone; one 3mg tablet per day for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Incidence of Adverse Events	12 Months (from the 1st dose to the end of study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Incidence of Skin Reactions: Number of Events		12 Months (from the 1st dose to the end of study)
Overall Incidence of Skin Reactions: Number of Participant Affected		12 Months (from the 1st dose to the end of study)
Columbia-Suicide Severity Rating Scale (C-SSRS) Item Responses	The C-SSRS is a physician-completed scale to assess any suicidal ideation and suicidal behavior. The C-SSRS contained questions about suicidal behavior and suicidal ideation. Subjects were placed into categories for suicidal behavior and for suicidal ideation based on their responses to various questions. Any suicidality was defined as suicidal behavior or suicidal ideation. The suicidal behavior categories were determined based on the response to the questions under suicidal behavior (Completed Suicide, Actual Attempt, Interrupted Attempt, Aborted Attempt, Preparatory Acts or Behavior).The suicidal ideation categories were determined by examining the response to 5 questions under suicidal ideation (Wish to be Dead, Nonspecific Active Suicidal Thoughts, Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act, Active Suicidal Ideation with Some Intent to Act, without Specific Plan, Active Suicidal Ideation with Specific Plan and Intent).	12 Months
Change From Baseline in Coding Copy Subtest A or B, or Digit Symbol Substitution Test (DSST)at Month 12	These tests are standardized information processing tasks to assess recognition and recoding of sensory information. The subject was given 90 seconds to complete as many substitutions of symbols as possible according to a code provided on top of the sheet. The Coding Copy Subtest A was used for subjects 6 to 7 years of age, the Coding Copy Subtest B was used for subjects 8 to 16 years of age, and the DSST was used for subjects 17 years of age. The DSST consists of rows containing small blank squares, each paired with a randomly assigned numbers 1-9. Above the rows is a key that pairs each number with a symbol. The subject must fill in the blank spaces with the matching symbol that is in the key. For the Subcopy tests the subject simply copies the symbol above each empty square. Scaled scores are used to account for age differences among test takers. Scaled scores range from 1 to 19, and higher scores indicate higher cognitive function.	Baseline and 12 Months (from the 1st dose to the end of study)
Clinical Global Impression (CGI) Improvement Score as Assessed by Parent/Caregiver or Child at Month 12	A 7-point scale was used for improvement with numeric values assigned to each of the responses: very much improved (1), much improved (2), minimally improved (3), no change (4), minimally worse (5), much worse (6), and very much worse (7).	Baseline and 12 Months (from the 1st dose to the end of study)
Change From Baseline at Month 12 in Subjective Sleep Latency (SL)	Sleep latency is the amount of time it takes to fall asleep after the lights have been turned off.	Baseline and 12 Months (from the 1st dose to the end of study)
Change From Baseline in Child Behavior Checklist (CBCL)	CBCL was completed by parents or guardians who saw the child in home-like settings. It includes several competence items, open-ended items for describing the child's illnesses, disabilities, concerns about the child, best things about the child, and several items to rate behavioral, emotional, and social problems. Responses are recorded on a Likert scale: 0 = Not True, 1 = Somewhat or Sometimes True, 2 = Very True or Often True. The checklist contains 120 questions. The standardized score is computed by determining the z-score by subtracting the mean for the subject's age group and gender from the raw score and then dividing this by the standard deviation for the subject's age group and gender. Next, multiply the zscore by 15 and then add 100. For activities scale, social scale, school scale, and total competence scale, higher values indicate higher competencies. For Internalizing problems, externalizing problems, and total problems, higher values indicate more problems.	Baseline and 12 Months (from the 1st dose to the end of study)
Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS)at Month 12	The PDSS total score ranges from a low of 0 where the individual is endorsing each item at the lowest level of daytime sleepiness to a high of 32 where the individual is endorsing each item at the highest level of daytime sleepiness.	Baseline and 12 Months (from the 1st dose to the end of study)
Change From Baseline in Conners' Continuous Performance Test II (CCPT II)	The CCPT-II is a computer-based 14-minute, visual-performance task. During an administration, respondents were required to press the space bar or click the mouse whenever any letter except the target letter appears on the screen. The speed at which the letters were presented varied during the administration. There were 6 blocks, with 3 sub-blocks, each containing 20 trials (letter presentations). The interstimulus intervals (ISIs) were 1, 2, and 4 seconds with a display time of 250 milliseconds. The order in which the different ISIs were presented varied between blocks. Conners' CCPT-II provides the following measures:% Omissions,% Commissions, Hit Reaction Time, Hit Reaction Time Standard Error,Variability of Standard Error, Detectability (d'), Response Style (beta), Perseverations, Hit Reaction Time Block Change (Vigilance Measure), Hit Standard Error Block Change (Vigilance Measure), Hit Reaction Time ISI change, and Hit Standard Error ISI Change, Confidence Index.	Baseline and 12 Months (from the 1st dose to the end of study)
Change From Baseline at Month 12 in Subjective Wake Time After Sleep Onset (WASO)	The sleep questionnaire, a Sponsor produced questionnaire used in previous eszopiclone studies, asked the subject or parent/guardian to report information about the subject's sleep and daytime functioning since the last visit. This questionnaire provided a subjective assessment of the subject's sleep over a predefined time period. WASO was assessed based on the responses to the sleep questionnaire.	Baseline and 12 Months (from the 1st dose to the end of study)
Change From Baseline at Month 12 in Subjective Number of Awakening After Sleep Onset (NAASO)	The sleep questionnaire, a Sponsor produced questionnaire used in previous eszopiclone studies, asked the subject or parent/guardian to report information about the subject's sleep and daytime functioning since the last visit. This questionnaire provided a subjective assessment of the subject's sleep over a predefined time period. NAASO was assessed based on the responses to the sleep questionnaire.	Baseline and 12 Months (from the 1st dose to the end of study)
Change From Baseline at Month 12 in Subjective Total Sleep Time (TST).	The sleep questionnaire, a Sponsor produced questionnaire used in previous eszopiclone studies, asked the subject or parent/guardian to report information about the subject's sleep and daytime functioning since the last visit. This questionnaire provided a subjective assessment of the subject's sleep over a predefined time period. TST was assessed based on the responses to the sleep questionnaire.	Baseline and 12 Months (from the 1st dose to the end of study)
Change From Baseline in Pediatric Quality of Life Scale	The SF-10™ Health Survey for Children is a 10-item care-giver completed assessment designed to measure children's health-related quality of life. The scale asked questions about the child's physical wellness, feelings, behavior, and activities at school and with family and friends. The SF-10 physical and psychosocial summary measures were scored such that higher scores indicated more favorable functioning. The Physical Summary Score is computed by summing values for questions 1, 2a, 2b, 3 and 5 and standardizing scores by normalizing to a total possible score of 0-100 with higher scores representing more positive indications. The Psychosocial Summary Score is computed by summing questions 4, 6, 7, 8, and 9 and standardizing scores by normalizing to a total possible score of 0-100 with higher scores representing more positive indications.	Baseline and 12 Months (from the 1st dose to the end of study)

Collaborators and Investigators

• Sponsor: Sunovion

Publications and helpful links

General Publications

• Sangal RB, Blumer JL, Lankford DA, Grinnell TA, Huang H. Eszopiclone for insomnia associated with attention-deficit/hyperactivity disorder. Pediatrics. 2014 Oct;134(4):e1095-103. doi: 10.1542/peds.2013-4221.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: March 4, 2009
• First Submitted That Met QC Criteria: March 5, 2009
• First Posted (Estimate): March 6, 2009

Study Record Updates

• Last Update Posted (Actual): October 26, 2017
• Last Update Submitted That Met QC Criteria: September 25, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Adolescent; Children; Attention Deficit Hyperactivity Disorder; Insomnia; Hypnotic; Eszopiclone
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Sleep Initiation and Maintenance Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Eszopiclone
• Other Study ID Numbers: 190-247

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No