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A Study of Pediatric Participants With Attention Deficit/Hyperactivity Disorder

Primary Purpose

Attention Deficit Hyperactivity Disorder

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Edivoxetine

About this trial

This is an interventional treatment trial for Attention Deficit Hyperactivity Disorder

Eligibility Criteria

6 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:

-Participants must meet Diagnostic and Statistical Manual of Mental Disorders 4th Ed (DSM-IV) diagnostic criteria for ADHD (inattentive, hyperactive/impulsive, or combined subtypes) based on an interview by an experienced clinician and confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present (SADS) and Lifetime Version (K-SADS-PL) at Visit 1 for new participants and in the parent trial for rollover participants.

-Participants must have an ADHDRS-IV-Parent: Inv total score of at least 1.5 standard deviations above the age/gender norm at both screening/randomization. New participants must have a Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder- Severity (CGI-ADHD-S) score greater than or equal to 4 at both screening/randomization.

Participants of child-bearing potential agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug. Female participants of child-bearing potential must test negative for pregnancy at the time of enrollment based on a urine pregnancy test.
Participants must have laboratory results, showing no clinically significant abnormalities.
Parents/participants must have a degree of understanding sufficient to communicate suitably with the investigator/ study coordinator.
Participants must be of normal intelligence.
Participants/parents must have been judged by the investigator to be reliable to keep appointments for clinic visits/all tests, including venipunctures and examinations required by the protocol.
Participants must be able to swallow tablets.

EXCLUSION CRITERIA:

Participants who weigh less than 16 kg at screening/randomization.
Female participants who are pregnant/breastfeeding.
Participants who have previously withdrawn/discontinued early from this study or any other study investigating Edivoxetine.
Participants who have a history of Bipolar I/II disorder, psychosis, or pervasive developmental disorder.
Participants with a history of any seizure disorder or known electroencephalographic (EEG) abnormalities in the absence of seizures.
Participants who are at serious suicidal risk.
Participants with a history of severe allergies to more than 1 class of medications, or multiple adverse drug reactions, or known hypersensitivity to Edivoxetine.
Participants with a history of alcohol or drug abuse/dependence within the past 3 months of screening, or who are currently using alcohol, drugs of abuse, or any prescribed or over-the-counter medication in a manner that the investigator considers indicative of abuse/dependence.
Participants who screen positive for drugs of abuse cannot participate.
Participants who have a medical condition that would increase sympathetic nervous system activity markedly, or who are taking a medication on a daily basis that has sympathomimetic activity are excluded.
Participants with problems that would be exacerbated by increased norepinephrine tone including a history of cardiovascular disease, thyroid dysfunction, glaucoma, or urinary retention.
Participants who at any time during the study are likely to need psychotropic medications apart from the drugs under study.
Participants who have used a monoamine oxidase inhibitor (MAOI) during the 2 weeks prior to randomization.
Participants with current or past history of clinically significant hypertension.
Participants who are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
Participants whose family anticipates a move outside the geographic range of the investigative site during participation in the study or who plan extended travel inconsistent with the recommended visit intervals.
Participants who, in the opinion of the investigator, are unsuitable in any other way to participate in this study.

Sites / Locations

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Edivoxetine

Arm Description

All enrolled participants were administered starting dose of 0.1 milligram per kilogram per day (mg/kg/day), or participant specific known stable dose, rollover participants (LNBJ [No NCT number]) and (LNBF [NCT00922636]), up to 0.3 mg/kg/day, oral, daily for up to 5 years.

Outcomes

Primary Outcome Measures

Percentage of Participants With At Least One Serious Adverse Events (SAE) Over the Duration of the Study

Percentage of Participants experienced at least one SAE during the study. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Number of Participants With At Least One SAE

Number of Participants experienced at least one SAE during the study. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Secondary Outcome Measures

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

Percentage of Participants had at least one TEAE during the study. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Number of Participants With At Least One TEAE

Number of participants had at least one TEAE during the study. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Percentage of Participants With Discontinuation Due to Adverse Events (DCAEs)

Number of Participants With At Least One DCAEs

Percentage of Participants Who Discontinued Due to Any Reason

Number of Participants Who Discontinued Due to Any Reason

Percentage of Participants With Columbia-Suicide Severity Rating Scale (CSSRS) for Each Category

Percentage of Participants in each category of CSSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Participants with suicidal ideation were those who had yes to any of the following questions: Wish to be dead, non-specific 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, and active suicidal ideation with specific plan and intent. Suicidal behavior included those who had yes to any of the following questions: Preparatory acts or behavior, Aborted attempt, Interrupted attempt, Non-fatal suicide attempt, Completed suicide.

Mean Change From Baseline Z-scores for Height

A z-score is the number of standard deviations a data point is from the mean. Z-scores range from -3 standard deviations (far left of the mean in normal distribution curve) up to +3 standard deviations (far right of the mean in normal distribution curve).

Mean Change From Baseline Z-Score for Weight

Mean Change From Baseline Z-Score in Body Mass Index (BMI)

Percentage of Participants With Response Rates

Number of Participants With a Response Rate

Survival Curve Time to Response

Percentage of Participants in Sexual Maturation on Tanners Scale

Participant's stage of sexual maturation were assessed using the Tanner staging measure for determining pubertal development in male and female participants. Tanner staging includes a self-assessment of pubic hair development (both males and females), genital development (males), and breast development (females). Tanner stage (pubic) is a score of range 1-5 where 1=no development and 5=adult pubic hair. Tanner stage (breast) is a score of range 1-5 where 1=no development and 5=adult breast. Tanner stages (1-5) were used to characterize physical development in children, adolescents, and adults. The stages were based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.

Number of Participants in Sexual Maturation on Tanners Scale

Percentage of Participants With Tobacco, Alcohol and Marijuana Use

Number of Participants With Tobacco, Alcohol and Marijuana Use

Mean Change From Baseline of Each Score Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) (Hyperactive/Impulsive, Inattentive and Total Score)

The ADHDRS-IV-Parent scale measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total score is computed as the sum of the 18 items and ranges from 0 to 54. Inattention and Hyperactivity-Impulsivity subscales consisted of 9 items each, for total subscale scores ranging from 0 to 27. Higher total and subscale scores are indicative of more severe symptoms. Least-squares (LS) mean change from baseline was adjusted for repeated measure analysis included baseline score and visit time in the model.

Mean Change From Baseline of Total Score Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity (CGI-ADHD-S)

The CGI-ADHD-S measures severity of the participants overall severity of ADHD symptoms. The score ranges from 1 to 7 (1=normal, not at all ill; 7=among the most extremely ill participants). LS mean change from baseline was adjusted for repeated measure analysis included baseline score and visit time in the model.

Mean Change of Total Score Teacher-rated Swanson Nolan, and Pelham Rating Scale-Revised (SNAP-IV) ADHD Subscales (Hyperactive/Impulsive, Inattentive and Total Score)

The SNAP-IV is a revision of the Swanson, Nolan, and Pelham (SNAP) Questionnaire (Swanson et al 1983). The SNAP-IV: ADHD Inattention Subscale (items 1-9) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores range from 0-27. Lower scores indicate a lesser intensity of inattention and higher scores a greater intensity. The SNAP-IV ADHD Hyperactivity/Impulsivity Subscale (items 10-18) scores the intensity of each item in the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores range from 0-27. Lower scores indicate a lesser intensity of hyperactivity/impulsivity and higher scores, a greater intensity. SNAP-IV ADHD Combined Scale score (inattention + hyperactivity/impulsivity) ranges from 0-54. A low score of 0 indicates less inattention + hyperactivity/impulsivity. A high score of 54 indicates more inattention + hyperactivity.

Mean Change From Baseline of Total Score SNAP-IV Oppositional Defiant Disorder (ODD) Subscale

The SNAP-IV ODD subscale includes items #21 to #28. Each item is scored on a 0 to 3 scale (0 = "Not At All", 1 = "Just A Little", 2 = "Pretty Much", 3 = "Very Much"). Score ranges from 0-24. The lowest possible score is 0; highest is 24. Higher scores indicate a greater presence of ODD and lowers scores a lower presence of ODD.

Mean Change From Baseline of Each Total Score Conners Comprehensive Behavior Rating Scales (CP-CBRS) Diagnostic and Statistical Manual of Mental Disorders, 4th Ed, Text Revision (DSM-IV-TR) for Symptom Subscales Manic Episode and Mixed Episode

The Conners CBRS measures behaviors, emotions, and academic problems in children and adolescents. DSM-IV-TR symptom scales is included and assesses the following disorders: ADHD, conduct disorder, ODD, major depressive episode, manic episode, mixed episode, generalized anxiety disorder, separation anxiety disorder, social phobia, obsessive compulsive disorder, autistic disorder, and Asperger's disorder. The age range suitable for this assessment is 6 to 18 years of age for parent form (203-item) and the teacher form (204-item) and 8 to18 years of age for the self-report form (179-item). The 203-item parent form of CP-CBRS was used in this study and completed by the parents/primary caregivers of the participants. Total score for each subscale is expressed as T-score based on gender/age norms: T-scores range from 0-100. Higher score indicates higher severity. Lower score indicate lower severity.

Mean Change From Baseline of Each Total Score CP-CBRS (DSM-IV-TR) ADHD Symptom Subscales (Hyperactive/Impulsive and Inattentive)

Mean Change From Baseline of Each Total Score CP-CBRS DSM-IV-TR for Oppositional Defiant Disorder (ODD), Anxiety, Conduct Disorder and Major Depressive Episode

Mean Change From Baseline of Each Raw Score CP-CBRS Impairment Items Subscales for Schoolwork/Grades, Friendship/Relationships, and Home Life

The Conners CBRS measures behaviors, emotions, and academic problems in children and adolescents. DSM-IV-TR symptom scales is included and assesses the following disorders: ADHD, conduct disorder, ODD, major depressive episode, manic episode, mixed episode, generalized anxiety disorder, separation anxiety disorder, social phobia, obsessive compulsive disorder, autistic disorder, and Asperger's disorder. The age range suitable for this assessment is 6 to 18 years of age for parent form (203-item) and the teacher form (204-item) and 8 to18 years of age for the self-report form (179-item). The 203-item parent form of CP-CBRS was used in this study and completed by the parents/primary caregivers of the participants. Schoolwork/grades, friendships/relationships, home life functioning scores range from 0=never to 3=very often. Raw scores are presented for each subscale with higher scores indicating higher severity and lower scores indicating lower severity.

Mean Change From Baseline of Each Total Score CP-CBRS Content Subscale for Aggressive Behaviors, Academic Difficulties, Social Problems, and Violence Potential)

CP-CBRS is a comprehensive assessment of a wide spectrum of behaviors, emotions, and academic problems in children and adolescents. It includes DSM-IV-TR symptom scales, empirical and rational scales, other clinical indicators and critical and impairment items. DSM-IV-TR symptom scales assess ADHD, conduct disorder, ODD, major depressive episode, manic episode, mixed episode, generalized anxiety disorder, separation anxiety disorder, social phobia, obsessive compulsive disorder, autistic disorder, and Asperger's disorder. The age range is 6 to 18 years of age for parent form (203-item) and the teacher form (204-item) and 8 to18 years of age self-report form (179-item). The parent form of Conners CBRS (CP-CBRS) was used in this study and completed by the parents/primary caregivers of the participants. Total score for each subscale is expressed as T-score based on gender/age norms: T-scores range from 0-100. Higher score indicates higher severity. Lower score indicate lower severity

Mean Change From Baseline of the 5 Domain Scores Child Health and Illness Profile-Adolescent Edition (CHIP-AE) in 5 Health Outcome Domains (Satisfaction, Comfort, Resilience, Risk Avoidance and Achievement)

CHIP-AE Child Report Form (CRF) is an adolescent rated assessment of their health status and level of functioning. The items in the 5 domains include: Achievement, Satisfaction, Comfort, Risk Avoidance, and Resilience. The majority of items assess frequency of activities or feelings using a 5-point response format (1=never, 5=always). Standard scores (T-scores) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Normative range is 40 to 60. Higher scores indicate better health and lower scores indicate worse health.

Mean Change From Baseline of the 5 Domain Scores Child Health and Illness Profile-Child Edition (CHIP-CE) in 5 Health Outcome Domains (Satisfaction, Comfort, Resilience, Risk Avoidance and Achievement)

CHIP-CE Parent Report Form (PRF) is a parent rated assessment of a child's health status/level of functioning. The achievement domain describes developmentally appropriate role functioning in school and with peers. The majority of items assess frequency of activities or feelings using a 5-point response format (1=never, 5=always). Standard scores (T-scores) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Normative range is 40 to 60. Higher scores indicate better health and lower scores indicate worse health.

Mean Change From Baseline of Total Score Euro-Qol Questionnaire - 5 Dimensions 3 Levels (EQ-5D-3L) Health State for Parent

The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life (QoL) instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The profile allows respondents to rate their health state in 5 health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of measure: no problems, some problems, and severe problems. The 5 dimensions of the health state profile are reported as a population-based (UK or US) health index score of theoretically possible health states ranging from 0-1; where 0 is death and 1 is perfect health. i.e., higher is better. Parents of the participants completed the EQ-5D-3L form for rating their own quality of life.

Mean Change From Baseline of Total Score EQ-5D-3L Visual Analog Scale (VAS) for Parent

The EQ-5D-3L is a generic, multidimensional, health-related, QoL instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The visual analog scale reported records the respondent's self-rated health state on a vertical line where the endpoints are labeled 100 being "best imaginable health state" and 0 being "worst imaginable health state." Parents of the participants complete EQ-5D-3L form for rating their own health.

Mean Change of From Baseline Total Score EQ-5D-3L Health State for Child

The EQ-5D-3L is a generic, multidimensional, health-related, QoL instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The profile allows respondents to rate their health state in 5 health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of measure: no problems, some problems, and severe problems. The 5 dimensions of the health state profile are reported as a population-based (UK or US) health index score of theoretically possible health states ranging from 0-1; where 0 is death and 1 is perfect health. Parents of the participants aged 6 to 11 years completed the EQ-5D-3L form regarding the participants health-related quality of life. i.e., young children were unable to assess their own quality of life so the parents assessed the child's quality of life for them.

Mean Change of From Baseline Total Score EQ-5D-3L VAS for Child

EQ-5D-3L is a generic, multidimensional, health-related, QoL instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The visual analog scale reported records the respondent's self-rated health state on a vertical line where the endpoints are labeled 100 being "best imaginable health state" and 0 being "worst imaginable health state." Parents of the participants aged 6 to 11 years complete the EQ-5D-3L form for rating the participants health-related QoL, EQ-5D-3L. i.e., the young child was unable to assess their own quality of life then the parent assessed the child's quality of life.

Mean Change From Baseline of Total Score EQ-5D-3L Health State for Adolescent

EQ-5D-3L is a generic, multidimensional, health-related, QoL instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The profile allows respondents to rate their health state in 5 health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of measure: no problems, some problems, and severe problems. The 5 dimensions of the health state profile are reported as a population-based (UK or US) health index score of theoretically possible health states ranging from 0-1; where 0 is death and 1 is perfect health. i.e., higher is better. Participants aged 12 years or older rate their own health-related quality of life using EQ-5D-3L.

Mean Change From Baseline of Total Score EQ-5D-3L VAS

EQ-5D-3L is a generic, multidimensional, health-related, QoL instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The visual analog scale reported records the respondent's self-rated health state on a vertical line where the endpoints are labeled 100 being "best imaginable health state" and 0 or being "worst imaginable health state." Participants aged 12 years or older rated their own health-related quality of life using the EQ-5D-3L VAS scale.

Mean Change From Baseline of Total Score Woodcock Johnson III Test of Achievement ([WJ III ACH])

The Woodcock Johnson (WJ III ACH) (Woodcock 2001) is designed to measure academic achievement and evaluates a person aged 2 to 90 years and the tool takes 60 to 160 minutes to complete depending on a person's academic level. The WJ III ACH has 2 parallel forms (A and B) that can be administered in an alternating fashion. The WCJ III ACH uses standard scores (Deviation IQ) with an average standard score of 100 and a standard deviation of 15. Higher scores indicate better abilities/achievements. Lower scores indicate worse abilities/achievements.

Mean Change From Baseline of Total Score Wide Range Achievement Test (WRAT 4)

The WRAT 4 is a norm-referenced test that measures the basic academic skills of word reading, sentence comprehension, spelling, and math computation. There are 2 alternate forms (Blue Form, Green Form) that can be used interchangeably with comparable results. It can be used to evaluate a person aged 5 to 94 years and the administration time is 30 to 45 minutes for children (8 years or older) and adults, and 15 to 25 minutes for young children (ages 5 to 7 years). The age-normed standard scores range from 55 - 145 and for each subtest/composite includes word reading, sentence comprehension, spelling, math computation and reading composite. Higher scores indicate better abilities/achievements. Lower scores indicate worse abilities/achievements.

Mean Change From Baseline of Total Score Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV)

The fourth edition of the WISC assessment (WISC-IV®) is administered to children ranging from 6 years to 16 years, 11 months. It contains 10 core subtests and 5 supplementary subtests, and takes 65-80 minutes to complete. In this study, Digit Span and Letter-Number Sequencing subtests were completed. Scaled scores range from 1 to 19. Higher scores denote better performance. Lower scores denote worse performance.

Mean Change From Baseline of Total Score Wechsler Adult Intelligence Scale - Third Edition (WAIS-III)

The WAIS-III® was used in the participants aged 17 years or older. Comprehensive reporting on the participant's intellectual ability is not required in this study. Raw scores for each of the 14 subtests are reported. Raw score ranges for each subtest are as follows: picture completion (0-25), vocabulary (0-66), digit symbol coding (0-133), similarities (0-33), block design (0-68), arithmetic (0-22), matrix reasoning (0-26), digit span forward and backward total (0-30), information (0-28), picture arrangement (0-22), comprehension (0-33), symbol search (0-60), letter-number sequencing (0-21), and object assembly (0-52). Higher scores reflect better performance and lower scores reflect lower performance.

Full Information

NCT ID

NCT00965419

First Posted

August 24, 2009

Last Updated

September 25, 2019

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00965419

Brief Title

A Study of Pediatric Participants With Attention Deficit/Hyperactivity Disorder

Official Title

Long-Term, Open-Label, Safety Study of LY2216684 in Pediatric Patients With Attention Deficit/Hyperactivity Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Terminated

Why Stopped

Terminated due to low 5 year completer number and not meeting primary objective.

Study Start Date

September 2009 (undefined)

Primary Completion Date

July 2015 (Actual)

Study Completion Date

July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The primary purpose of the study is to assess long-term safety and tolerability of Edivoxetine in pediatric participants with attention deficit hyperactive disorder (ADHD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Attention Deficit Hyperactivity Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

267 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Edivoxetine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Edivoxetine

Other Intervention Name(s)

LY2216684

Intervention Description

0.1 mg/kg/day or participant specific known stable dose, rollover participants (LNBJ [No NCT number]) and (LNBF [NCT00922636]), up to 0.3 mg/kg/day, oral, daily for up to 5 years.

Primary Outcome Measure Information:

Title

Percentage of Participants With At Least One Serious Adverse Events (SAE) Over the Duration of the Study

Description

Percentage of Participants experienced at least one SAE during the study. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Time Frame

Baseline Through Week 252

Title

Number of Participants With At Least One SAE

Description

Number of Participants experienced at least one SAE during the study. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Time Frame

Baseline Through Week 252

Secondary Outcome Measure Information:

Title

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

Description

Percentage of Participants had at least one TEAE during the study. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Time Frame

Baseline Through Week 252

Title

Number of Participants With At Least One TEAE

Description

Number of participants had at least one TEAE during the study. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Time Frame

Baseline Through Week 252

Title

Percentage of Participants With Discontinuation Due to Adverse Events (DCAEs)

Time Frame

Baseline Through Week 252

Title

Number of Participants With At Least One DCAEs

Time Frame

Baseline Through Week 252

Title

Percentage of Participants Who Discontinued Due to Any Reason

Time Frame

Baseline Through Week 252

Title

Number of Participants Who Discontinued Due to Any Reason

Time Frame

Baseline Through Week 252

Title

Percentage of Participants With Columbia-Suicide Severity Rating Scale (CSSRS) for Each Category

Description

Time Frame

Baseline Through Week 252, Baseline, 1-month (mo) Follow-Up (f/u)

Title

Mean Change From Baseline Z-scores for Height

Description

Time Frame

Baseline, Week 60; Baseline, Week 240

Title

Mean Change From Baseline Z-Score for Weight

Description

Time Frame

Baseline, Week 60; Baseline, Week 240

Title

Mean Change From Baseline Z-Score in Body Mass Index (BMI)

Time Frame

Baseline, Week 60; Baseline, Week 240

Title

Percentage of Participants With Response Rates

Time Frame

Week 12

Title

Number of Participants With a Response Rate

Time Frame

Week 12

Title

Survival Curve Time to Response

Time Frame

Week 12

Title

Percentage of Participants in Sexual Maturation on Tanners Scale

Description

Time Frame

Baseline Up to Week 252

Title

Number of Participants in Sexual Maturation on Tanners Scale

Description

Time Frame

Baseline Up to Week 252

Title

Percentage of Participants With Tobacco, Alcohol and Marijuana Use

Time Frame

Week 60 through Week 252

Title

Number of Participants With Tobacco, Alcohol and Marijuana Use

Time Frame

Week 60 through Week 252

Title

Description

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change From Baseline of Total Score Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity (CGI-ADHD-S)

Description

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change of Total Score Teacher-rated Swanson Nolan, and Pelham Rating Scale-Revised (SNAP-IV) ADHD Subscales (Hyperactive/Impulsive, Inattentive and Total Score)

Description

Time Frame

Baseline, Week 12

Title

Mean Change From Baseline of Total Score SNAP-IV Oppositional Defiant Disorder (ODD) Subscale

Description

Time Frame

Baseline, Week 12

Title

Description

Time Frame

Baseline, Week 60; Baseline, Week 252

Title

Mean Change From Baseline of Each Total Score CP-CBRS (DSM-IV-TR) ADHD Symptom Subscales (Hyperactive/Impulsive and Inattentive)

Description

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change From Baseline of Each Total Score CP-CBRS DSM-IV-TR for Oppositional Defiant Disorder (ODD), Anxiety, Conduct Disorder and Major Depressive Episode

Description

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change From Baseline of Each Raw Score CP-CBRS Impairment Items Subscales for Schoolwork/Grades, Friendship/Relationships, and Home Life

Description

The Conners CBRS measures behaviors, emotions, and academic problems in children and adolescents. DSM-IV-TR symptom scales is included and assesses the following disorders: ADHD, conduct disorder, ODD, major depressive episode, manic episode, mixed episode, generalized anxiety disorder, separation anxiety disorder, social phobia, obsessive compulsive disorder, autistic disorder, and Asperger's disorder. The age range suitable for this assessment is 6 to 18 years of age for parent form (203-item) and the teacher form (204-item) and 8 to18 years of age for the self-report form (179-item). The 203-item parent form of CP-CBRS was used in this study and completed by the parents/primary caregivers of the participants. Schoolwork/grades, friendships/relationships, home life functioning scores range from 0=never to 3=very often. Raw scores are presented for each subscale with higher scores indicating higher severity and lower scores indicating lower severity.

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change From Baseline of Each Total Score CP-CBRS Content Subscale for Aggressive Behaviors, Academic Difficulties, Social Problems, and Violence Potential)

Description

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Description

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 156

Title

Description

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 156

Title

Mean Change From Baseline of Total Score Euro-Qol Questionnaire - 5 Dimensions 3 Levels (EQ-5D-3L) Health State for Parent

Description

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change From Baseline of Total Score EQ-5D-3L Visual Analog Scale (VAS) for Parent

Description

The EQ-5D-3L is a generic, multidimensional, health-related, QoL instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The visual analog scale reported records the respondent's self-rated health state on a vertical line where the endpoints are labeled 100 being "best imaginable health state" and 0 being "worst imaginable health state." Parents of the participants complete EQ-5D-3L form for rating their own health.

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change of From Baseline Total Score EQ-5D-3L Health State for Child

Description

The EQ-5D-3L is a generic, multidimensional, health-related, QoL instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The profile allows respondents to rate their health state in 5 health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of measure: no problems, some problems, and severe problems. The 5 dimensions of the health state profile are reported as a population-based (UK or US) health index score of theoretically possible health states ranging from 0-1; where 0 is death and 1 is perfect health. Parents of the participants aged 6 to 11 years completed the EQ-5D-3L form regarding the participants health-related quality of life. i.e., young children were unable to assess their own quality of life so the parents assessed the child's quality of life for them.

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change of From Baseline Total Score EQ-5D-3L VAS for Child

Description

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change From Baseline of Total Score EQ-5D-3L Health State for Adolescent

Description

EQ-5D-3L is a generic, multidimensional, health-related, QoL instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The profile allows respondents to rate their health state in 5 health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of measure: no problems, some problems, and severe problems. The 5 dimensions of the health state profile are reported as a population-based (UK or US) health index score of theoretically possible health states ranging from 0-1; where 0 is death and 1 is perfect health. i.e., higher is better. Participants aged 12 years or older rate their own health-related quality of life using EQ-5D-3L.

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change From Baseline of Total Score EQ-5D-3L VAS

Description

EQ-5D-3L is a generic, multidimensional, health-related, QoL instrument that contains 2 parts: a health status profile and a visual analog scale to rate global health-related QoL. The visual analog scale reported records the respondent's self-rated health state on a vertical line where the endpoints are labeled 100 being "best imaginable health state" and 0 or being "worst imaginable health state." Participants aged 12 years or older rated their own health-related quality of life using the EQ-5D-3L VAS scale.

Time Frame

Baseline, Week 12; Baseline, Week 60; Baseline, Week 252

Title

Mean Change From Baseline of Total Score Woodcock Johnson III Test of Achievement ([WJ III ACH])

Description

Time Frame

Baseline, Week 60

Title

Mean Change From Baseline of Total Score Wide Range Achievement Test (WRAT 4)

Description

Time Frame

Baseline, Week 60

Title

Mean Change From Baseline of Total Score Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV)

Description

Time Frame

Baseline, Week 60

Title

Mean Change From Baseline of Total Score Wechsler Adult Intelligence Scale - Third Edition (WAIS-III)

Description

Time Frame

Baseline, Week 60

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA: -Participants must meet Diagnostic and Statistical Manual of Mental Disorders 4th Ed (DSM-IV) diagnostic criteria for ADHD (inattentive, hyperactive/impulsive, or combined subtypes) based on an interview by an experienced clinician and confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present (SADS) and Lifetime Version (K-SADS-PL) at Visit 1 for new participants and in the parent trial for rollover participants. -Participants must have an ADHDRS-IV-Parent: Inv total score of at least 1.5 standard deviations above the age/gender norm at both screening/randomization. New participants must have a Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder- Severity (CGI-ADHD-S) score greater than or equal to 4 at both screening/randomization. Participants of child-bearing potential agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug. Female participants of child-bearing potential must test negative for pregnancy at the time of enrollment based on a urine pregnancy test. Participants must have laboratory results, showing no clinically significant abnormalities. Parents/participants must have a degree of understanding sufficient to communicate suitably with the investigator/ study coordinator. Participants must be of normal intelligence. Participants/parents must have been judged by the investigator to be reliable to keep appointments for clinic visits/all tests, including venipunctures and examinations required by the protocol. Participants must be able to swallow tablets. EXCLUSION CRITERIA: Participants who weigh less than 16 kg at screening/randomization. Female participants who are pregnant/breastfeeding. Participants who have previously withdrawn/discontinued early from this study or any other study investigating Edivoxetine. Participants who have a history of Bipolar I/II disorder, psychosis, or pervasive developmental disorder. Participants with a history of any seizure disorder or known electroencephalographic (EEG) abnormalities in the absence of seizures. Participants who are at serious suicidal risk. Participants with a history of severe allergies to more than 1 class of medications, or multiple adverse drug reactions, or known hypersensitivity to Edivoxetine. Participants with a history of alcohol or drug abuse/dependence within the past 3 months of screening, or who are currently using alcohol, drugs of abuse, or any prescribed or over-the-counter medication in a manner that the investigator considers indicative of abuse/dependence. Participants who screen positive for drugs of abuse cannot participate. Participants who have a medical condition that would increase sympathetic nervous system activity markedly, or who are taking a medication on a daily basis that has sympathomimetic activity are excluded. Participants with problems that would be exacerbated by increased norepinephrine tone including a history of cardiovascular disease, thyroid dysfunction, glaucoma, or urinary retention. Participants who at any time during the study are likely to need psychotropic medications apart from the drugs under study. Participants who have used a monoamine oxidase inhibitor (MAOI) during the 2 weeks prior to randomization. Participants with current or past history of clinically significant hypertension. Participants who are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Participants whose family anticipates a move outside the geographic range of the investigative site during participation in the study or who plan extended travel inconsistent with the recommended visit intervals. Participants who, in the opinion of the investigator, are unsuitable in any other way to participate in this study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

City

Spring Valley

State/Province

California

ZIP/Postal Code

91978

Country

United States

Facility Name

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32607

Country

United States

Facility Name

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

City

University Park

State/Province

Florida

ZIP/Postal Code

34201

Country

United States

Facility Name

City

Smyrna

State/Province

Georgia

ZIP/Postal Code

30080

Country

United States

Facility Name

City

Libertyville

State/Province

Illinois

ZIP/Postal Code

60048

Country

United States

Facility Name

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

City

Rochester Hills

State/Province

Michigan

ZIP/Postal Code

48307

Country

United States

Facility Name

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198

Country

United States

Facility Name

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89128

Country

United States

Facility Name

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19139

Country

United States

Facility Name

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38117

Country

United States

Facility Name

City

Lake Jackson

State/Province

Texas

ZIP/Postal Code

77566

Country

United States

Facility Name

City

Lubbock

State/Province

Texas

ZIP/Postal Code

79423

Country

United States

Facility Name

City

Herndon

State/Province

Virginia

ZIP/Postal Code

20170

Country

United States

Facility Name

City

Seattle

State/Province

Washington

ZIP/Postal Code

98104

Country

United States

Facility Name

City

Kelowna

State/Province

British Columbia

ZIP/Postal Code

V1Y 1Z9

Country

Canada

Facility Name

City

Santurce

ZIP/Postal Code

00912

Country

Puerto Rico

Facility Name

City

Kuei Shan Hsiang

ZIP/Postal Code

33305

Country

Taiwan

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing URL

https://vivli.org/

Learn more about this trial

A Study of Pediatric Participants With Attention Deficit/Hyperactivity Disorder

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