A Randomized, Double-Blind, Placebo-Controlled, Crossover, Laboratory Classroom Study to Evaluate the Safety and Efficacy of d-Amphetamine Transdermal Drug Delivery System (d-ATS) Compared to Placebo in Children and Adolescents With ADHD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 3
- 主要终点
- Mean Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Total Score During the Double-Blind Treatment Period
研究概览
简要总结
This study will evaluate safety and efficacy of d-Amphetamine Transdermal System for the treatment of Attention Deficit Hyperactivity Disorder in children and adolescents.
详细描述
The study will consist of a four-week screening period, a 3-day wash-out period (if applicable), a five-week open-label, step-wise dose optimization period and two-week double blind randomized crossover treatment period with weekly classroom assessments and a safety follow-up by telephone 7 - 10 days after last dose of study drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gender: Male or female
- •Age: Between 6 and 17 years of age (inclusive)
- •Race: All eligible
- •Females of child-bearing potential must have agreed to practice a clinically accepted method of contraception during the study and for at least 1 month prior to study dosing and 1 month following completion of the study. Acceptable contraceptive methods included abstinence, oral contraception, surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), intrauterine device, diaphragm in addition to spermicidal foam and condom on male partner, or systemic contraception (e.g., Norplant System)
- •Must have met Diagnostic and Statistical Manual of Mental Disorders, 4th edition - Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD combined, hyperactive/impulsive subtype, or predominately inattentive subtype
- •The Screening and Baseline visit ADHD-RS-IV total score must have been ≥90% of the general population of children by age and gender
- •Able to wear a patch for 9 hours (for children and, if applicable, for adolescents, parent or caregiver must be present to apply and remove the patches and maintain the used and unused patches in a secure, controlled area of the home)
- •Functioning at an age-appropriate level intellectually as determined by an intelligence quotient (IQ) of ≥80 on the Wechsler Abbreviated Scale of Intelligence II™ (WASI II™) vocabulary and matrix reasoning components
- •Must have been able to complete PERMP assessment
- •Must have provided parental consent (signed ICF) and obtained written/verbal assent from the subject
- •Subject and parent(s)/ caregiver must have been willing and able to comply with all the protocol requirements and parent(s) or caregiver must be able to provide transportation for the subject to and from the analog classroom sessions
排除标准
- •Blood pressure outside the 95th percentile for age and gender
- •Pulse of <50 (age 6 - 17), or >120 (age 6 - 12), or >125 (age 13 - 17)
- •Known non-responder to amphetamine treatment
- •Documented allergy, intolerance, or hypersensitivity to amphetamine
- •Currently taking an ADHD medication that is providing symptom control with no residual impairment at home or school and has acceptable tolerability and adherence
- •Recent history (within the past 6 months) of suspected substance abuse or dependence disorder (including nicotine)
- •History of seizures during the last 2 years (excluding infantile febrile seizures), a tic disorder (exclusive of transient tic disorder), a current diagnosis, and/or a family history of Tourette's Disorder. Mild medication-induced tics were not exclusionary
- •Any psychiatric disorder that could interfere with study participation or the safety of the subject or other participants, such as conduct disorder (CD) or oppositional defiant disorder (ODD) with a history of prominent aggressive outbursts. Children meeting CD or ODD but without prominent aggression will be allowed to enroll at the discretion of the Investigator
- •Autism or Asperger's Disorder
- •Family history (first degree relatives) of sudden cardiac death
- •Current controlled (requiring medication) or uncontrolled comorbid psychiatric conditions such as post-traumatic stress disorder, psychosis, bipolar illness, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder, was considered a suicide risk, had recent (last 6 months) suicidal ideation, or any lifetime self-harm event
- •History of abnormal thyroid function
- •Has a body mass index (BMI) for age greater than 95th percentile per Centers for Disease Control BMI (for gender-specific charts)
- •Known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug
- •Any skin abnormality present at the potential application site (i.e., infection, rash, atrophy, excessive fragility or dryness, any cut or abrasion, or tattoo)
- •History of hypersensitivity, allergy to topical medication, preparation, or adhesive dressings
- •Concurrent chronic or significant acute illnesses (such as severe allergic rhinitis or an infectious process requiring antibiotics, unless expected to resolve or has resolved by Day 0) disability or any unstable medical condition that in the Investigator's opinion would lead to difficulty complying with the protocol requirements
- •Used any investigational drug within 30 days of the Screening visit
- •History of physical, sexual, or emotional abuse in the last year
- •Medical history of hepatitis A/B/C or HIV
- •Positive urine drug screen for drugs of abuse
研究组 & 干预措施
d-Amphetamine Transdermal patch
The study was conducted in 2 parts: a 5-week, open-label, step-wise Dose Optimization Period and a 2-week, randomized, cross-over Double-Blind Treatment Period.
Subjects who reached the optimal dose by end of dose optimization treatment period were randomized to receive double-blind treatment.
Participants first received study patches everyday for one week, then subjects were crossed-over to receive the placebo treatment.
d-Amphetamine Transdermal System: Patches will be worn for 9 hours every day. After 9 hours the patch will be removed. Every day a new patch will be applied.
干预措施: d-Amphetamine Transdermal Patch (Drug)
Placebo patch
The study was conducted in 2 parts: a 5-week, open-label, step-wise Dose Optimization Period and a 2-week, randomized, cross-over Double-Blind Treatment Period.
Subjects who reached the optimal dose by end of dose optimization treatment period were randomized to receive double-blind treatment.
Participants first received placebo patches everyday for one week, then subjects were crossed-over to receive the study treatment.
Placebo patch: Patches will be worn for 9 hours every day. After 9 hours the patch will be removed. Every day a new patch will be applied.
干预措施: Placebo patch (Drug)
结局指标
主要结局
Mean Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Total Score During the Double-Blind Treatment Period
时间窗: Mean SKAMP Total Score of SKAMP Total Scores from 9 different time points including (1, 2, 3, 4.5, 6, 7, 9, 10, 12 hours post-dose)
The SKAMP total score comprises all 13 items. The SKAMP was designed for independent observers to rate 13 items representing 2 factors of classroom behavior: attention (SKAMP-A) and deportment (SKAMP-D), as well as quality of work. Items are specific to place (classroom setting) \& time (during a typical classroom period), \& the scale is used to assess multiple ratings taken within a day. The SKAMP-D subscale evaluates deportment, including interacting with other children, interacting with adults, remaining quiet according to classroom rules, \& staying seated according to classroom rules. The SKAMP-A subscale is a measure of attention \& evaluates getting started on assignments, sticking with tasks, attending to an activity, and making activity transitions. The SKAMP quality of work subscale includes 3 items: completing assigned work, performing work accurately, and being careful and neat while writing or drawing. Scores range from 0-78 with higher scores indicating worse impairment.
次要结局
- Onset of Efficacy Measured by Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Total Score(Onset of efficacy defined as the time of the first assessment time showing statistical significance between d-ATS and placebo. 2 hours post-dose in Double-Blind Treatment Period)
- Duration of Effect for d-Amphetamine and Placebo Treatment(Duration of Effect was from onset (2 hours post-dose) and up to 12 hours post-dose (p<0.001))
- Permanent Product Measure of Performance (PERMP) Scores Including PREMP-C and PREMP-A From Different Timepoints Post-dose(1,2, 3, 4.5,6,7,9,10 and 12 hours post-dose from double-blind treatment period)
- Number of Responders Evaluated by Clinical Global Impression (CGI-I) Scale by Treatments From the Double-blind Treatment Period(the double-blind treatment period)
- Change in the Clinician-rated Scale of ADHD Symptoms Based on DSM-IV-TR Criteria (ADHD-RS-IV).(Averaged from week 6 and week 7 results during the Double-Blind Cross-Over treatment period.)
- Conners Parent Rating Scale Revised Short Form (CPRS-R:S) Total Scores From Week 6 and Week 7(Combined analysis by treatment groups from week 6 and week 7 (averaged))