Attention Deficit Hyperactivity DisorderPhase 2/3NCT00922636
A Study of Pediatric Patients With Attention Deficit/Hyperactivity Disorder
A Phase 2/3 study testing LY2216684 and Methylphenidate in people with Attention Deficit Hyperactivity Disorder, run by Eli Lilly and Company at 19 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- What is being tested?
- LY2216684 and Methylphenidate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 340 participants
- Where
- 19 sitesin 3 countries
- Study dates
- Jun 2009to Dec 2010
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
19 sites in 3 countries.
19 sites in 3 countries
United States17 sites
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.
Bradenton, Florida, 34208
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.
Canton, Ohio, 44718
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, 32607
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, 20170
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, 46202
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, 77566
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, 89128
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.
Lincoln, Nebraska, 68510
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, 79423
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.
Media, Pennsylvania, 19063
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, 38119
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.
Norristown, Pennsylvania, 19401
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, 68198
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, 32806
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.
Portland, Oregon, 97210
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, 91978
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.
Wharton, Texas, 77488
Canada1 site
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, V1Y 1Z9
Puerto Rico1 site
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, 00912
About this study
Official title: A Fixed-Dose, Randomized, Double-Blind, Placebo-Controlled Study of LY2216684 in Pediatric Patients With Attention Deficit/Hyperactivity Disorder
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.
- Conditions
- Attention Deficit Hyperactivity Disorder
- Being tested
- LY2216684, Methylphenidate, Placebo (tablet), Placebo (capsule)
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY2216684Drug
Also called Edivoxetine
Taken in tablet form QD po.
MethylphenidateDrug
Extended-release methylphenidate 18 mg/day to 54 mg/day, based on weight, QD po as a capsule for the 8-week double-blind treatment phase.
Placebo (tablet)Drug
Placebo given as a tablet for LY2216684 blind QD po for the 8-week double-blind treatment phase, followed by 2 weeks in the taper phase.
Placebo (capsule)Drug
Placebo given as a capsule for methylphenidate blind QD po for the 8-week double-blind treatment phase followed by 2 weeks in the taper phase.
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate | Active comparator | Extended-release methylphenidate 18 milligrams per day (mg/day) to 54 mg/day, based on weight, given once daily (QD) and orally (po) as a capsule for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the taper phase. Receives: Drug: Methylphenidate |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo (tablet); Drug: Placebo (capsule) |
| LY2216684 (0.1 mg/kg/day) | Experimental | Taken in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the taper phase. Receives: Drug: LY2216684 |
| LY2216684 (0.2 mg/kg/day) | Experimental | Taken in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the taper phase. Receives: Drug: LY2216684 |
| LY2216684 (0.3 mg/kg/day) | Experimental | Taken in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the taper phase. Receives: Drug: LY2216684 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Assesses 18 Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD diagnosis symptoms/severity in past week. Each item: 0 (none/never, rarely) to 3 (severe/very often). Total score ranges from 0 to 54. Higher total scores indicate greater illness severity. Change scores=Week 8 score-baseline score. Least Squares (LS) Mean Change adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Assesses 18 Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD diagnosis symptoms/severity in past week. Each item: 0 (none/never, rarely) to 3 (severe/very often). Total score ranges from 0 to 54. Higher total scores indicate greater illness severity. Change scores=Week 8 score-baseline score. LS Mean Change adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Secondary outcomes (52)
Change From Baseline in the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder Subscale (SNAP-IV: ADHD) Total Score at Week 8
Includes Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD criteria for inattention (items 1-9) and hyperactivity/impulsivity (items 11-19) symptom subsets. Item score: 0 (not at all) to 3 (very much) rating scale. Total score is average of 18 items. Higher total scores=greater ADHD symptoms. Least Squares Mean change is adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and the continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Includes Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD criteria for inattention (items 1-9) and hyperactivity/impulsivity (items 11-19) symptom subsets. Item score: 0 (not at all) to 3 (very much) rating scale. Total score is average of 18 items. Higher total scores=greater ADHD symptoms. Least Squares Mean change is adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and the continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
The CP-CBRS academic difficulties total/language/math subscale score is a measure of academic performance. Each subscale item score ranges from 0 (never, seldom) to 3 (very often, very frequently). Total score is expressed as T-score based on gender/age norms. Academic difficulties T-score range: 0-100. Higher T-scores denote greater academic difficulties. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline total score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
The CP-CBRS academic difficulties total/language/math subscale score is a measure of academic performance. Each subscale item score ranges from 0 (never, seldom) to 3 (very often, very frequently). Total score is expressed as T-score based on gender/age norms. Academic difficulties T-score range: 0-100. Higher T-scores denote greater academic difficulties. Change scores=Week 8 score-baseline score. Least Squares Mean Change is adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline total score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) Total Score at Week 8
Measures participant's overall ADHD symptom severity. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Higher scores represent greater illness severity. Change scores=Week 8 score-baseline score. The Least Squares (LS) Mean Change was based on the fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, as well as the continuous, fixed effects of baseline CGI-S score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Measures participant's overall ADHD symptom severity. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Higher scores represent greater illness severity. Change scores=Week 8 score-baseline score. The Least Squares (LS) Mean Change was based on the fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, as well as the continuous, fixed effects of baseline CGI-S score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) Endpoint Score During the Treatment Phase (Weeks 1-8)
Measures total improvement (or worsening) of a participant's ADHD symptoms from the beginning of treatment. Scores range from 1 (very much improved) to 7 (very much worsened). Lower scores represent greater improvement. Least Squares (LS) Mean Change for weeks 1-8 is from a restricted maximum likelihood-based, mixed model repeated measure analysis. The model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction.
Measured: Weeks 1 through 8
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
Measures total improvement (or worsening) of a participant's ADHD symptoms from the beginning of treatment. Scores range from 1 (very much improved) to 7 (very much worsened). Lower scores represent greater improvement. Least Squares (LS) Mean Change for weeks 1-8 is from a restricted maximum likelihood-based, mixed model repeated measure analysis. The model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction.
Measured: Weeks 1 through 8
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
Measures ADHD symptom severity. Individual items on each subscale are scored from 0 (never) to 3 (very often). Total score expressed as T-score based on gender/age norms. Subscale total T-scores (0-100); higher T-scores=greater symptom severity. Least Squares Mean Change is from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline total score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Measures ADHD symptom severity. Individual items on each subscale are scored from 0 (never) to 3 (very often). Total score expressed as T-score based on gender/age norms. Subscale total T-scores (0-100); higher T-scores=greater symptom severity. Least Squares Mean Change is from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline total score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Swanson, Nolan and Pelham (SNAP-IV) Oppositional Defiant Disorder (ODD) Total Score at Week 8
Measures oppositional defiance disorder symptoms. Total scores range from 0 (not at all) to 3 (very much). Higher total scores represent greater ODD. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline total score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Measures oppositional defiance disorder symptoms. Total scores range from 0 (not at all) to 3 (very much). Higher total scores represent greater ODD. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline total score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8
Rates schoolwork/grades, friendships/relationships, home life functioning (0=never to 3=very often). Total score expressed as a T-score based on gender/age norms (range 0-100). Higher T-score=greater symptom severity. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Rates schoolwork/grades, friendships/relationships, home life functioning (0=never to 3=very often). Total score expressed as a T-score based on gender/age norms (range 0-100). Higher T-score=greater symptom severity. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8
Captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a "yes" answer to any of 3 suicidal behavior questions: preparatory acts or behavior, aborted attempt, and interrupted attempt. Suicidal ideation: "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a "yes" answer to actual attempt or completed suicide, nonfatal suicide attempt, and completed suicide.
Measured: 8 weeks
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
Captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a "yes" answer to any of 3 suicidal behavior questions: preparatory acts or behavior, aborted attempt, and interrupted attempt. Suicidal ideation: "yes" answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a "yes" answer to actual attempt or completed suicide, nonfatal suicide attempt, and completed suicide.
Measured: 8 weeks
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
Measures manic symptom severity. Individual subscale items range: 0 (never) to 3 (very often). Total score expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater symptom severity. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Measures manic symptom severity. Individual subscale items range: 0 (never) to 3 (very often). Total score expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater symptom severity. Change scores=Week 8 score-baseline score. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8
Assess aggressive behaviors, academic difficulties, social problems, violence potential. Individual subscale items range: 0=never to 3=very often. Total expressed as T-score based on gender/age norms (0-100). Change scores=Week 8 score-baseline score. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score, baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 in Stimulant Naive Methylphenidate Group
Assess aggressive behaviors, academic difficulties, social problems, violence potential. Individual subscale items range: 0=never to 3=very often. Total expressed as T-score based on gender/age norms (0-100). Change scores=Week 8 score-baseline score. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score, baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8
Assesses adolescent's health status/functioning level. Domains: Achievement, Satisfaction, Comfort, Risk Avoidance, Resilience. Items assess frequency of activities/feelings (1=never, 5=always). Standard scores (T-scores) calculated for all domains by adjusting raw scores based on established reference group mean, standard deviation (T-scores mean=50, standard deviation=10). Higher scores=better health. Least Squares (LS) Mean Change from analysis of covariance model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), and baseline score.
Measured: Baseline, 8 weeks
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 in Stimulant Naive Methylphenidate Group
Assesses adolescent's health status/functioning level. Domains: Achievement, Satisfaction, Comfort, Risk Avoidance, Resilience. Items assess frequency of activities/feelings (1=never, 5=always). Standard scores (T-scores) calculated for all domains by adjusting raw scores based on established reference group mean, standard deviation (T-scores mean=50, standard deviation=10). Higher scores=better health. Least squares (LS) mean of the change from baseline to endpoint (week 8) is from an ANCOVA model. The model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), and baseline CHIP-AE domain score.
Measured: Baseline, 8 weeks
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8
76-item parent-rated assessment of child's health status/functioning level. Most items assess frequency of activities/feelings (1=never, 5=always). Standard scores (T-scores) were calculated for all domains by adjusting raw scores based on an established reference group mean and standard deviation (T-scores mean=50, standard deviation=10). Higher scores denote improvement. Least Squares (LS) Mean Change is from an analysis of covariance model that included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), and baseline domain score.
Measured: Baseline, 8 weeks
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 in Stimulant Naive Methylphenidate Group
76-item parent-rated assessment of child's health status/functioning level. Most items assess frequency of activities/feelings (1=never, 5=always). Standard scores (T-scores) were calculated for all domains by adjusting raw scores based on an established reference group mean and standard deviation (T-scores mean=50, standard deviation=10). Higher scores denote improvement. Least Squares (LS) Mean Change is from an analysis of ANCOVA model that included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), and baseline domain score.
Measured: Baseline, 8 weeks
Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Letter-Number Sequencing Score at Week 8
Working memory subtest. Task involves sequencing, mental manipulation, attention, short-term memory, visual spatial imaging, and processing speed; consists of 10 items, 3 trials each. Scaled scores range: 1 to 19. Higher scores denote better performance. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis that included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Working memory subtest. Task involves sequencing, mental manipulation, attention, short-term memory, visual spatial imaging, and processing speed; consists of 10 items, 3 trials each. Scaled scores range: 1 to 19. Higher scores denote better performance. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis that included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8
Assesses ability to accurately and rapidly recognize and name visual symbols. The tests consist of rapid automatized naming tests (that is, Letters, Numbers, Objects, Colors) and 2 rapid alternating stimulus tests (that is, 2-Set Letters and Numbers; 3-Set Letters, Numbers, and Colors). Scores are based on the amount of time required to name all the stimulus items in each test section. Raw scores were converted to standard scores based on participant's age and conversion tables from manual (mean=100, standard deviation=15). Higher scores=better ability. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group
Assesses ability to accurately and rapidly recognize and name visual symbols. The tests consist of rapid automatized naming tests (that is, Letters, Numbers, Objects, Colors) and 2 rapid alternating stimulus tests (that is, 2-Set Letters and Numbers; 3-Set Letters, Numbers, and Colors). Scores are based on the amount of time required to name all the stimulus items in each test section. Raw scores were converted to standard scores based on participant's age and conversion tables from manual (mean=100, standard deviation=15). Higher scores=better ability. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Assess ODD symptom severity. Individual subscale items range from 0 (never) to 3 (very often/frequently). Total is expressed as a T-score based on gender/age norms (range 0-100). Higher T-score=greater ODD. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Assess ODD symptom severity. Individual subscale items range from 0 (never) to 3 (very often/frequently). Total is expressed as a T-score based on gender/age norms (range 0-100). Higher T-score=greater ODD. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Assess anxiety symptom severity. Individual subscale items: 0 (never, seldom) - 3 (very often/frequently). Total score expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater anxiety. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Assess anxiety symptom severity. Individual subscale items: 0 (never, seldom) - 3 (very often/frequently). Total score expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater anxiety. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Conduct Disorder Symptom Subscale Score at Week 8
Assess conduct disorder symptom severity. Individual subscale items: 0 (never/seldom) - 3 (very often/frequently). Total expressed as T-score based on gender/age norms (0-100). Higher T-score=greater conduct disorder. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Assess conduct disorder symptom severity. Individual subscale items: 0 (never/seldom) - 3 (very often/frequently). Total expressed as T-score based on gender/age norms (0-100). Higher T-score=greater conduct disorder. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Major Depressive Episode Score at Week 8
Assess depressive symptom severity. Individual subscale items range: 0 (never, seldom) to 3 (very often/frequently). Total expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater depression. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Assess depressive symptom severity. Individual subscale items range: 0 (never, seldom) to 3 (very often/frequently). Total expressed as T-score based on gender/age norms (0-100). Higher T-scores=greater depression. Change scores=Week 8 score-baseline score. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Total Score at Week 8
Parent-completed 11-item questionnaire (3 morning items, 8 evening items) on a scale of 0 (no difficulty) to 3 (a lot of difficulty). Total score ranges from 0 to 33; higher score=greater difficulty in evening and morning behavior. Least Squares (LS) Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and includes fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Parent-completed 11-item questionnaire (3 morning items, 8 evening items) on a scale of 0 (no difficulty) to 3 (a lot of difficulty). Total score ranges from 0 to 33; higher score=greater difficulty in evening and morning behavior. Least Squares (LS) Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and includes fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Morning Summary Score at Week 8
Measures difficulty level of 3 common morning behaviors (for example, get out of bed) from 0 (no difficulty) to 3 (a lot of difficulty). Total score range is from 0 to 9; a higher score indicates greater difficulty in morning behavior. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and includes fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline morning score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Measures difficulty level of 3 common morning behaviors (for example, get out of bed) from 0 (no difficulty) to 3 (a lot of difficulty). Total score range is from 0 to 9; a higher score indicates greater difficulty in morning behavior. Least Squares (LS) Mean Change from restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and includes fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline morning score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R ) Evening Summary Score at Week 8
Measures difficulty level of 8 common evening behaviors (for example, sit through dinner) from 0 (no difficulty) to 3 (a lot of difficulty). Total score ranges: 0 to 24; higher scores indicate greater difficulty in evening behavior. Least Squares (LS) Mean Change is from restricted maximum likelihood-based, mixed model repeated measure analysis (MMRM) and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline evening score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Measures difficulty level of 8 common evening behaviors (for example, sit through dinner) from 0 (no difficulty) to 3 (a lot of difficulty). Total score ranges: 0 to 24; higher scores indicate greater difficulty in evening behavior. Least Squares (LS) Mean Change is from restricted maximum likelihood-based, mixed model repeated measure analysis (MMRM) and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline evening score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Mixed Episode Score at Week 8
The mixed episode score does not exist in the Conners CBRS scale; therefore no analyses could be conducted.
Measured: Baseline, 8 weeks
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
The mixed episode score does not exist in the Conners CBRS scale; therefore no analyses could be conducted.
Measured: Baseline, 8 weeks
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
Measures ADHD diagnostic symptoms (0=none/never-3=severe/very often). Inattention=sum odd items; hyperactivity-impulsivity=sum even items (subtotal: 0-27). Total scores: 0-54. High score=greater illness severity. Missing data-imputation in manual was applied. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the ADHDRS-IV-Parent:Inv Hyperactivity-Impulsivity and Inattention Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group
Measures ADHD diagnostic symptoms (0=none/never-3=severe/very often). Inattention=sum odd items; hyperactivity-impulsivity=sum even items (subtotal: 0-27). Total scores: 0-54. High score=greater illness severity. Missing data-imputation in manual was applied. Least Squares Mean Change from restricted maximum likelihood-based, mixed model repeated measure analysis; included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Total Score at Week 8
A working memory subtest of WISC-IV, a measure of attention; concentration; sequencing; number facility; and auditory short-term memory. Scaled scores range from 1 to 19. Higher scores denote better performance. Least Squares (LS) Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, as well as the continuous, fixed effects of baseline Digit Span total score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
A working memory subtest of WISC-IV, a measure of attention; concentration; sequencing; number facility; and auditory short-term memory. Scaled scores range from 1 to 19. Higher scores denote better performance. Least Squares (LS) Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure (MMRM) analysis and included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, as well as the continuous, fixed effects of baseline Digit Span total score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Digit Span Subtotal Scores at Week 8
Measures attention, concentration, sequencing, number facility, and auditory short-term memory. Digit forward and digit backward subscales each comprise 2 trials and 8 items. Scaled scores range from 1 to 19. Higher scores denote better performance. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
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
Measures attention, concentration, sequencing, number facility, and auditory short-term memory. Digit forward and digit backward subscales each comprise 2 trials and 8 items. Scaled scores range from 1 to 19. Higher scores denote better performance. Least Squares Mean Change is from a restricted maximum likelihood-based, mixed model repeated measure analysis. Model included fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
Measured: Baseline, 8 weeks
Number of Participants With a Response (Response Rate) up to Week 8
Response rate analysis compared the frequency of response between LY2216684 treatment groups versus placebo for participants who had a final study period II (weeks 1-8) Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered and Scored (ADHD-RS-IV-PV:IR) total score <=60% of their baseline total score. ADHD-RS-IV-PV:IR measures 18 symptoms in Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) ADHD diagnosis. Item scores range: 0 (none/never or rarely) to 3 (severe/very often). Total scores range: 0 to 54.
Measured: Baseline, up to 8 weeks
Number of Participants With a Response (Response Rate) up to Week 8 in Stimulant Naive Methylphenidate Group
Response rate analysis compared the frequency of response between LY2216684 treatment groups versus placebo for participants who had a final study period II (weeks 1-8) Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version:Investigator-Administered and Scored (ADHD-RS-IV-PV:IR) total score <=60% of their baseline total score. ADHD-RS-IV-PV:IR measures 18 symptoms in Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) ADHD diagnosis. Item scores range: 0 (none/never or rarely) to 3 (severe/very often). Total scores range: 0 to 54.
Measured: Baseline, up to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Hyperactivity DisorderStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 340 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00922636
- Sponsor's protocol ID
- 10925
- Other IDs
- H9P-MC-LNBF
- Status last verified
- Jul 2014
- First submitted
- 16 Jun 2009
- Last updated
- 18 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24840045
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Fixed-Dose, Randomized, Double-Blind, Placebo-Controlled Study of LY2216684 in Pediatric Patients With Attention Deficit/Hyperactivity Disorder
- ClinicalTrials.gov ID
- NCT00922636
- Acronym / sponsor ID
- 10925
- Conditions
- Attention Deficit Hyperactivity Disorder
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 340 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 17 Jun 2009 (estimated)
- Results
- Posted 18 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate | Active comparator | Drug: MethylphenidateExtended-release methylphenidate 18 milligrams per day (mg/day) to 54 mg/day, based on weight, given once daily (QD) and orally (po) as a capsule for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the taper phase. |
| Placebo | Placebo comparator | Drug: Placebo (tablet), Drug: Placebo (capsule) |
| LY2216684 (0.1 mg/kg/day) | Experimental | Drug: LY2216684Taken in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of placebo in the taper phase. |
| LY2216684 (0.2 mg/kg/day) | Experimental | Drug: LY2216684Taken in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the taper phase. |
| LY2216684 (0.3 mg/kg/day) | Experimental | Drug: LY2216684Taken in tablet form QD po for the 8-week double-blind treatment phase, followed by 2 weeks of tapering in the taper phase. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LY2216684Also: EdivoxetineTaken in tablet form QD po. | Drug | LY2216684 (0.1 mg/kg/day), LY2216684 (0.2 mg/kg/day), LY2216684 (0.3 mg/kg/day) |
| MethylphenidateExtended-release methylphenidate 18 mg/day to 54 mg/day, based on weight, QD po as a capsule for the 8-week double-blind treatment phase. | Drug | Methylphenidate |
| Placebo (tablet)Placebo given as a tablet for LY2216684 blind QD po for the 8-week double-blind treatment phase, followed by 2 weeks in the taper phase. | Drug | Placebo |
| Placebo (capsule)Placebo given as a capsule for methylphenidate blind QD po for the 8-week double-blind treatment phase followed by 2 weeks in the taper phase. | Drug | Placebo |
Primary outcome
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
Time frame: Baseline, 8 weeks
Assesses 18 Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD diagnosis symptoms/severity in past week. Each item: 0 (none/never, rarely) to 3 (severe/very often). Total score ranges from 0 to 54. Higher total scores indicate greater illness severity. Change scores=Week 8 score-baseline score. Least Squares (LS) Mean Change adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
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
Time frame: Baseline, 8 weeks
Assesses 18 Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision ADHD diagnosis symptoms/severity in past week. Each item: 0 (none/never, rarely) to 3 (severe/very often). Total score ranges from 0 to 54. Higher total scores indicate greater illness severity. Change scores=Week 8 score-baseline score. LS Mean Change adjusted for fixed class effects of treatment, pooled investigative site, strata (prior stimulant use status), visit, and treatment*visit interaction, and continuous, fixed effects of baseline score and baseline score*visit interaction.
52 secondary outcomes
Change From Baseline in the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder Subscale (SNAP-IV: ADHD) Total Score at Week 8
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Change From Baseline in the Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) Total Score at Week 8
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale (CGI-ADHD-I) Endpoint Score During the Treatment Phase (Weeks 1-8)
Time frame: Weeks 1 through 8
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
Time frame: Weeks 1 through 8
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
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Change From Baseline in the Swanson, Nolan and Pelham (SNAP-IV) Oppositional Defiant Disorder (ODD) Total Score at Week 8
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Impairment Items Subscales-Total Score at Week 8
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 8
Time frame: 8 weeks
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
Time frame: 8 weeks
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
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8
Time frame: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS) Content Subscales - Total Score at Week 8 in Stimulant Naive Methylphenidate Group
Time frame: Baseline, 8 weeks
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8
Time frame: Baseline, 8 weeks
Change From Baseline in the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) Domain Scores at Week 8 in Stimulant Naive Methylphenidate Group
Time frame: Baseline, 8 weeks
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8
Time frame: Baseline, 8 weeks
Change From Baseline in the Child Health and Illness Profile - Child Edition (CHIP-CE) at Week 8 in Stimulant Naive Methylphenidate Group
Time frame: Baseline, 8 weeks
Change From Baseline in the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) Letter-Number Sequencing Score at Week 8
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8
Time frame: Baseline, 8 weeks
Change From Baseline in the Rapid Automatized Naming/Rapid Alternating Stimulus Test (RAN/RAS) Subtotal Scores at Week 8 in Stimulant Naive Methylphenidate Group
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Conduct Disorder Symptom Subscale Score at Week 8
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Change From Baseline in the Conners' Comprehensive Behavior Rating Scale (CP-CBRS DSM-IV-TR) Major Depressive Episode Score at Week 8
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Total Score at Week 8
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Change From Baseline in the Weekly Parent Ratings of Evening and Morning Behavior-Revised (WPREMB-R) Morning Summary Score at Week 8
Time frame: Baseline, 8 weeks
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
Time frame: Baseline, 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24840045Lin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
19 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing LY2216684 and Methylphenidate in people with Attention Deficit Hyperactivity Disorder, run by Eli Lilly and Company at 19 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Canada, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Baseline, 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00922636, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2014.