Clinical trial NCT00922636: A Study of Pediatric Patients With Attention Deficit/Hyperactivity Disorder
Official title: A Fixed-Dose, Randomized, Double-Blind, Placebo-Controlled Study of LY2216684 in Pediatric Patients With Attention Deficit/Hyperactivity Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Attention Deficit Hyperactivity Disorder
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-06-17
Enrollment: 340
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of your child's participation in this study is to determine whether LY2216684 can help pediatric patients with attention-deficit/hyperactivity disorder (ADHD); and assess the safety of LY2216684 and any side effects that might be associated with it.


Eligibility criteria: Inclusion Criteria:

* Patients must meet Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnostic criteria for ADHD based on Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime (K-SADS-PL) prior to randomization.
* Patients must have an Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered and Scored (ADHD-RS-IV-PV:IR) total score at least 1.5 standard deviations above the age/gender norm prior to randomization. They must have a Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) score greater than or equal to 4 at both the patients screening visit, prior to randomization.
* Patients must have laboratory results; showing no clinically significant abnormalities.
* Patients must be of normal intelligence, as assessed by the investigator.
* Patients/parents must have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests, including venous punctures and examinations required by the protocol.
* Patients 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 patients of child-bearing potential must test negative for pregnancy at the time of enrollment based on a urine pregnancy test.

Exclusion Criteria:

* Patients who weigh less than 18 kg or greater than 75 kg at screening and at randomization.
* Female patients who are pregnant or who are breast-feeding. Patients who have a history of Bipolar I/ II, psychosis, or pervasive developmental disorder.
* Patients who have current motor tics or a diagnosis of Tourette's Syndrome.
* Patients with marked anxiety, tension, and agitation sufficient, to contraindicate treatment with extended-release methylphenidate.
* Patients with a history of any seizure disorder, known electroencephalographic (EEG) abnormalities in the absence of seizures.
* If the electrocardiogram (ECG) assessed at screening/prior to randomization shows an abnormality meeting one or more of the absolute exclusion criteria listed in the Pediatric ECG Alert Criteria must be excluded from the study.
* Patients who, in the opinion of the investigator, are at serious suicidal risk.
* Patients with a history of severe allergies to more than one class of medications, multiple adverse drug reactions, or known hypersensitivity to extended-release methylphenidate.
* Patients with a history of alcohol or drug abuse within the past 3 months prior to, 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.
* Patients who screen positive for drugs of abuse not prescribed by a physician cannot participate. Drug screen may be repeated at the discretion of the investigator, and the patient may be allowed to enter the study if the repeat screen is negative. All patients must have a negative drug screen before enrollment in the study.
* Patients 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. Such medications can be taken on an as-needed basis.
* Patients with problems that would be exacerbated by increased norepinephrine tone, including a history of cardiovascular disease, thyroid dysfunction, glaucoma, urinary retention, or severe gastrointestinal narrowing.
* Patients who, at any time during the study, are likely to need psychotropic medications apart from the drugs under study.
* Patients who, at any time during the study, are likely to begin structured psychotherapy aimed at ADHD symptoms are excluded. Psychotherapy initiated at least 1 month prior to screening is acceptable.
* Patients who have used a monoamine oxidase inhibitor (MAOI) during the 2 weeks prior to randomization.
* Patients with current or past history of clinically significant hypertension.
* Patients 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.
* Patients who have participated in a prior study of LY2216684.

Primary outcomes:
measure: Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered and Scored (ADHD-RS-IV-PV:IR) Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered and Scored (ADHD-RS-IV-PV:IR) Total Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
Secondary outcomes:
measure: Change From Baseline in the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder Subscale (SNAP-IV: ADHD) Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder Subscale (SNAP-IV: ADHD) Total Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Academic Difficulties Total Score and the Language and Math Subscales at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Academic Difficulties Total Score and the Language and Math Subscales at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) Total Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) Endpoint Score During the Treatment Phase (Weeks 1-8)
timeFrame: Weeks 1 through 8
measure: Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) Endpoint Score During the Treatment Phase (Weeks 1-8) in Stimulant Naive Methylphenidate Group
timeFrame: Weeks 1 through 8
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR ADHD) Predominantly Hyperactive-Impulsive Type and Predominantly Inattentive Type Total Score and Symptom Scores at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the CP-CBRS DSM-IV-TR ADHD Predominantly Hyperactive-Impulsive Type and Predominantly Inattentive Type Total Score and Symptom Scores at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Swanson, Nolan and Pelham (SNAP-IV) Oppositional Defiant Disorder (ODD) Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Swanson, Nolan and Pelham (SNAP-IV) Oppositional Defiant Disorder (ODD) Total Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8
timeFrame: 8 weeks
measure: Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Symptom Subscale for Manic Episode - Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Symptom Subscale for Manic Episode - Total Score at 8 Weeks in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Letter-Number Sequencing Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Letter-Number Sequencing Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Symptom Subscale for Oppositional Defiant Disorder (ODD) Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Symptom Subscale for Oppositional Defiant Disorder (ODD) Total Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Generalized Anxiety Disorder (GAD) and Separation Anxiety Disorder Symptom Subscales at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Generalized Anxiety Disorder (GAD) and Separation Anxiety Disorder Symptom Subscales at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Conduct Disorder Symptom Subscale Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Conduct Disorder Symptom Subscale Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Major Depressive Episode Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Major Depressive Episode Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Total Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Morning Summary Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Morning Summary Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R ) Evening Summary Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R ) Evening Summary Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Mixed Episode Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Mixed Episode Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Hyperactivity-Impulsivity and Inattention Subtotal Scores at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the ADHDRS-IV-Parent:Inv Hyperactivity-Impulsivity and Inattention Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Total Score at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Total Score at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Subtotal Scores at Week 8
timeFrame: Baseline, 8 weeks
measure: Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, 8 weeks
measure: Number of Participants With a Response (Response Rate) up to Week 8
timeFrame: Baseline, up to 8 weeks
measure: Number of Participants With a Response (Response Rate) up to Week 8 in Stimulant Naive Methylphenidate Group
timeFrame: Baseline, up to 8 weeks
Other outcomes:
Locations:
city: Spring Valley
country: United States
facility: 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.
state: California
city: Bradenton
country: United States
facility: 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.
state: Florida
city: Gainesville
country: United States
facility: 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.
state: Florida
city: Orlando
country: United States
facility: 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.
state: Florida
city: Indianapolis
country: United States
facility: 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.
state: Indiana
city: Lincoln
country: United States
facility: 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.
state: Nebraska
city: Omaha
country: United States
facility: 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.
state: Nebraska
city: Las Vegas
country: United States
facility: 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.
state: Nevada
city: Canton
country: United States
facility: 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.
state: Ohio
city: Portland
country: United States
facility: 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.
state: Oregon
city: Media
country: United States
facility: 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.
state: Pennsylvania
city: Norristown
country: United States
facility: 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.
state: Pennsylvania
city: Memphis
country: United States
facility: 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.
state: Tennessee
city: Lake Jackson
country: United States
facility: 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.
state: Texas
city: Lubbock
country: United States
facility: 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.
state: Texas
city: Wharton
country: United States
facility: 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.
state: Texas
city: Herndon
country: United States
facility: 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.
state: Virginia
city: Kelowna
country: Canada
facility: 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.
state: British Columbia
city: Santurce
country: Puerto Rico
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Lin DY, Kratochvil CJ, Xu W, Jin L, D'Souza DN, Kielbasa W, Allen AJ. A randomized trial of edivoxetine in pediatric patients with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2014 May;24(4):190-200. doi: 10.1089/cap.2013.0043.