A Study of Pediatric Participants With Attention Deficit/Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00965419
• Other study ID #: 11332
• Secondary ID: H9P-MC-LNDH
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: September 2009
• Est. completion date: July 2015

Study information

• Verified date: September 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 267
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Disease
• Hyperkinesis

Intervention

Drug:
• Edivoxetine
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.

Locations

Country	Name	City	State
Canada	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.	Kelowna	British Columbia
Puerto Rico	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.	Santurce
Taiwan	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.	Kuei Shan Hsiang
United States	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.	Gainesville	Florida
United States	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.	Herndon	Virginia
United States	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.	Indianapolis	Indiana
United States	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.	Lake Jackson	Texas
United States	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.	Las Vegas	Nevada
United States	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.	Libertyville	Illinois
United States	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.	Lubbock	Texas
United States	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.	Memphis	Tennessee
United States	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.	Omaha	Nebraska
United States	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.	Orlando	Florida
United States	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.	Philadelphia	Pennsylvania
United States	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.	Rochester Hills	Michigan
United States	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.	Seattle	Washington
United States	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.	Smyrna	Georgia
United States	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.	Spring Valley	California
United States	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.	University Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline Through Week 252
Primary	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.	Baseline Through Week 252
Secondary	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.	Baseline Through Week 252
Secondary	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.	Baseline Through Week 252
Secondary	Percentage of Participants With Discontinuation Due to Adverse Events (DCAEs)		Baseline Through Week 252
Secondary	Number of Participants With At Least One DCAEs		Baseline Through Week 252
Secondary	Percentage of Participants Who Discontinued Due to Any Reason		Baseline Through Week 252
Secondary	Number of Participants Who Discontinued Due to Any Reason		Baseline Through Week 252
Secondary	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.	Baseline Through Week 252, Baseline, 1-month (mo) Follow-Up (f/u)
Secondary	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).	Baseline, Week 60; Baseline, Week 240
Secondary	Mean Change From Baseline Z-Score for Weight	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).	Baseline, Week 60; Baseline, Week 240
Secondary	Mean Change From Baseline Z-Score in Body Mass Index (BMI)		Baseline, Week 60; Baseline, Week 240
Secondary	Percentage of Participants With Response Rates		Week 12
Secondary	Number of Participants With a Response Rate		Week 12
Secondary	Survival Curve Time to Response		Week 12
Secondary	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.	Baseline Up to Week 252
Secondary	Number 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.	Baseline Up to Week 252
Secondary	Percentage of Participants With Tobacco, Alcohol and Marijuana Use		Week 60 through Week 252
Secondary	Number of Participants With Tobacco, Alcohol and Marijuana Use		Week 60 through Week 252
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 12
Secondary	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.	Baseline, Week 12
Secondary	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.	Baseline, Week 60; Baseline, Week 252
Secondary	Mean Change From Baseline of Each Total Score CP-CBRS (DSM-IV-TR) ADHD Symptom Subscales (Hyperactive/Impulsive and Inattentive)	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 156
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 156
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 12; Baseline, Week 60; Baseline, Week 252
Secondary	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.	Baseline, Week 60
Secondary	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.	Baseline, Week 60
Secondary	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.	Baseline, Week 60
Secondary	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.	Baseline, Week 60