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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sunovion
ClinicalTrials.gov Identifier:
NCT00857220
First received: March 4, 2009
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Insomnia
Attention Deficit Hyperactivity Disorder
Drug: eszopiclone
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Sunovion:

Primary Outcome Measures:
  • Overall Incidence of Adverse Events [ Time Frame: 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall Incidence of Skin Reactions: Number of Events [ Time Frame: 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: Yes ]
  • Overall Incidence of Skin Reactions: Number of Participant Affected [ Time Frame: 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: Yes ]
  • Clinical Laboratory Assessments [ Time Frame: Day -30 to -1, Day 0, Week 2(for treatment naive pts), and Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ] [ Designated as safety issue: No ]
  • Vital Sign Measurements [ Time Frame: Day -14 to -1, Day 0, Week 2, and Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ] [ Designated as safety issue: No ]
  • Orthostatic Effects [ Time Frame: Day -14 to -1, Day 0, Week 2 (for treatment naive pts) , and Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 ] [ Designated as safety issue: No ]
  • 12 Lead ECG Parameters [ Time Frame: Day -30 to -1, and Months 1 and 12 ] [ Designated as safety issue: No ]
  • Physical Examinations [ Time Frame: Day -30 to -1, and Months 1, 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
  • Neurologic Examinations [ Time Frame: Day -14 to -1, and Months 1, 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
  • Columbia-Suicide Severity Rating Scale (C-SSRS) Item Responses [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
    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).

  • Change From Baseline in Coding Copy Subtest A or B, or Digit Symbol Substitution Test (DSST)at Month 12 [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impression (CGI) Improvement Score as Assessed by Parent/Caregiver or Child at Month 12 [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline at Month 12 in Subjective Sleep Latency (SL) [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    Sleep latency is the amount of time it takes to fall asleep after the lights have been turned off.

  • Change From Baseline in Child Behavior Checklist (CBCL) [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS)at Month 12 [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Conners' Continuous Performance Test II (CCPT II) [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline at Month 12 in Subjective Wake Time After Sleep Onset (WASO) [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline at Month 12 in Subjective Number of Awakening After Sleep Onset (NAASO) [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline at Month 12 in Subjective Total Sleep Time (TST). [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Pediatric Quality of Life Scale [ Time Frame: Baseline and 12 Months (from the 1st dose to the end of study) ] [ Designated as safety issue: No ]
    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.


Enrollment: 304
Study Start Date: May 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00857220

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

No publications provided

Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT00857220     History of Changes
Other Study ID Numbers: 190-247
Study First Received: March 4, 2009
Results First Received: November 2, 2012
Last Updated: June 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sunovion:
Hypnotic
Eszopiclone
Attention Deficit Hyperactivity Disorder
Insomnia
Children
Adolescent

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Disease
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Pathologic Processes
Eszopiclone
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014