A Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Aptensio XR® in Children Ages 4 to Under 6 Years Diagnosed With Attention Deficit-Hyperactivity Disorder (ADHD)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 158
- 试验地点
- 2
- 主要终点
- Attention Deficit Hyperactivity Disorder Rating Scale - 4th Edition (ADHD-RS-IV) Preschool Version Total Score Change From End of Open Label Phase (Baseline) to End of Double Blind.
研究概览
简要总结
This randomized, double-blind, flexible-dose, placebo-controlled, parallel group study is designed to evaluate Aptensio XR® compared to placebo in preschool age children with ADHD. Male and female children ages 4 years, 0 months to 5 years, 8 months with a diagnosis of ADHD (combined, inattentive or hyperactive/impulsive) will be enrolled.
There will be 6 phases in this study: a screening phase of up to 4 weeks, which will include washout if applicable, an enrollment & parent training phase lasting 2-4 weeks, an eligibility phase of up to 2 weeks to determine eligibility for the open-label phase, a 6-week open-label dose titration phase, a 2 week double-blind phase for Aptensio XR® responders, and a two-week follow-up call after study completion or early discontinuation to assess for ongoing adverse events and concomitant medications.
Up to 150 subjects will be enrolled in this trial to allow for subjects who improve significantly during the behavior training phase and drop-outs. Once 74 subjects have completed the double-blind phase, no additional subjects will be enrolled in the trial. Subjects who are already enrolled at that time will be allowed to complete the trial.
The primary objective of this study is to establish that an optimal dose of Aptensio XR® will result in a significant reduction in ADHD symptoms compared with placebo in children ages 4 to under 6 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Blinded active capsules looked identical to the same strength placebo capsules
入排标准
- 年龄范围
- 4 Years 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects ages 48 months to 68 months inclusive at time of consent
- •Met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for ADHD, combined, hyperactive/impulsive or inattentive presentation made during a clinical interview by an experienced clinician and confirmed with Kiddie-Sads-Present and Lifetime Version (K-SADS-PL)
- •ADHD symptoms must have been present for at least 6 months
- •Age- and sex-adjusted ratings of ≥ 90th percentile Total Score on the ADHD-RS-IV Preschool Version
- •Score of < 65 on the Child Global Assessment Scale (CGAS)
- •Must have had a CGI-S score of ≥ 4 at Visit 2 (subjects who were granted a waiver to bypass parental training, and did not have a Visit 2, were still qualified to continue in the study based on their CGI-S score at screening)
- •Estimated intelligence quotient (IQ) ≥ 80 on the Kaufman Brief Intelligence Test, 2nd edition (KBIT-2). If results from the KBIT-2 were deemed invalid because of significant ADHD symptomatology, the PI could submit additional documentation to support average cognitive functioning. This documentation could include progress reports from preschool or other previous testing. These exceptions were evaluated by the Medical Monitor and Study PIs on a case-by-case basis for inclusion.
- •The subject had a parent or legal guardian who would give written informed consent for the subject to participate in the study
- •Subject and parent or legal guardian must have been able to speak and understand English
- •Subject must live with primary caretaker/rater and have been living with primary caretaker for at least 6 months
- •Subject and parent/guardian must have been willing and able to comply with all requirements of the protocol
- •Systolic and diastolic blood pressure below the 95th percentile for age and gender
排除标准
- •The subject had a lack of response to a trial of adequate dose and duration of MPH or intolerance to previous methylphenidate (MPH) treatment
- •The subject was using any other current psychotropic medication except clonidine, guanfacine, atomoxetine and/or stimulants or had taken an investigational drug in the 30 days prior to screening
- •The subject had used monoamine oxidase inhibitors (MAOIs) within 14 days of the screening visit
- •The subject planned to use prohibited drugs or agents at any point between the screening visit and the end of the study
- •Use of anticonvulsants, antidepressants, or antipsychotics in the 30 days prior to screening
- •The subject should not plan to start any additional psychotherapy outside of the trial during the duration of the study
- •The subject had a history of chronic vocal or motor tics or Tourette's syndrome
- •The subject had any clinically significant ECG abnormalities at screening
- •The subject had any major medical conditions that would have interfered with involvement in the study or could have been affected negatively by methylphenidate
- •The subject had chronic medical illnesses including a seizure disorder (excluding a history of febrile seizures), severe hypertension, untreated thyroid disease, known structural cardiac abnormalities, serious arrhythmias, cardiomyopathy, glaucoma, or a family history of sudden death
- •History (in the past 12 months) or presence of clinically-significant cardiovascular, cerebrovascular, renal, hepatic, gastrointestinal, pulmonary, immunological, hematological, endocrine, or neurological disease that in the opinion of the investigator could have put the subject at risk if he/she participated in the trial or which could have confounded study results
- •Family history (parent or sibling) of structural cardiovascular disease
- •Current or recent (past 12 months) history of drug abuse in someone living in the subject's home
- •Current symptoms or history of major psychiatric illness (for example schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder, depression, severe anxiety disorder, obsessive compulsive disorder or autistic spectrum disorder) in addition to ADHD that required treatment with additional medication or, in the opinion of the PI, would have contraindicated study participation
- •History or presence of suicidal ideation or significant self-injurious behavior
- •The subject showed evidence of current physical, sexual, or emotional abuse
- •Both biological parents of the subject had a history of bipolar disorder
研究组 & 干预措施
Aptensio XR
Optimized dose of Aptensio XR (10, 15, 20, 30 or 40 mg Aptensio XR)
干预措施: Aptensio XR (Drug)
Placebo comparator
Placebo capsules
干预措施: Placebo (Drug)
结局指标
主要结局
Attention Deficit Hyperactivity Disorder Rating Scale - 4th Edition (ADHD-RS-IV) Preschool Version Total Score Change From End of Open Label Phase (Baseline) to End of Double Blind.
时间窗: 2 weeks: End of open label phase (Baseline) at study day 84 to end of double blind treatment at study day 98.
ADHD-RS-IV is 18-item scale incorporates each of the ADHD symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) regardless of assigned subtype. Scoring was based on the universally accepted symptom severity as recommended in the DSM-IV-TR manual on a 4-point scale: 0 = never or rarely, 1 = sometimes, 2 = often, and 3 = very often. The total score is the sum of the scores for all 18 items and could range from 0 (no impairment) to 54 (maximal impairment) for each administration per subject. Higher score means higher frequency and severity of symptoms. Trained clinicians administered the questionnaire to parents. The ADHD-RS-IV Preschool Version was used to determine eligibility, optimal dosing and the efficacy of double blind treatment.
次要结局
- Attention Deficit Hyperactivity Disorder Rating Scale - 4th Edition (ADHD-RS-IV) Preschool Version Hyperactivity-Impulsivity Subscale Score Change From End of Open Label Phase (Baseline) to End of Double Blind.(2 weeks: End of open label phase (Baseline) at study day 84 to end of double blind treatment at study day 98.)
- Attention Deficit Hyperactivity Disorder Rating Scale - 4th Edition (ADHD-RS-IV) Preschool Version Inattention Subscale Score Change From End of Open Label Phase (Baseline) to End of Double Blind.(2 weeks: End of open label phase (Baseline) at study day 84 to end of double blind treatment at study day 98.)
- Summary of Clinical Global Impression Scale of Severity (CGI-S) Score From End of Open Label Phase (Baseline) to End of Double Blind.(2 weeks: End of open label phase (Baseline) at study day 84 to end of double blind treatment at study day 98.)
- Conners Early Childhood Behavior - Parent (Short) (EC BEH-P(S)) Change in T-score From End of Open Label Phase (Baseline) to End of Double Blind(2 weeks: End of open label phase (Baseline) at study day 84 to end of double blind treatment at study day 98.)
- Clinical Global Impression Scale of Improvement (CGI-I) Score at End of Double Blind Phase Relative to End of Open Label Phase (Baseline).(2 weeks: End of open label phase (Baseline) at study day 84 to end of double blind treatment at study day 98.)