A Phase 3, Randomized, Double-blind, Multicenter, Parallel-group, Placebo-controlled, Fixed-Dose Safety and Efficacy Study of SPD489 Compared With Placebo in Preschool Children Aged 4-5 Years With Attention-deficit/Hyperactivity Disorder
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 199
- 试验地点
- 48
- 主要终点
- Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6
研究概览
简要总结
The purpose of this study is to determine if an investigational treatment is effective in improving the total score on the ADHD-RS-IV Preschool Version in children 4-5 years old diagnosed with ADHD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 4 Years 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is a male or female aged 4-5 years inclusive at the time of consent
- •Participant's parent(s) or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) by the participant before completing any study related procedures.
- •Participant and parent(s)/LAR are willing and able to comply with all of the testing and requirements defined in the protocol, including oversight of morning dosing.
- •Participant must meet DSM-IV-TR criteria for a primary diagnosis of ADHD (any sub-type).
- •Participant has an ADHD-RS-IV Preschool Version Total Score at the baseline visit (Visit 0) greater than or equal to 28 for boys, and greater than or equal to 24 for girls.
- •Participant has a Clinical Global Impressions - Severity of Illness (CGI-S) score greater than or equal to 4 at the baseline visit (Visit 0).
- •Participant has a Peabody Picture Vocabulary Test standard score of greater than or equal to 70 at the screening visit (Visit -1).
- •Participant has undergone an adequate course of non-pharmacological treatment or has a severe enough condition to consider enrollment without undergoing prior non-pharmacological treatment.
- •Participant has participated in a structured group activity (e.g, preschool, sports, Sunday school) so as to assess symptoms and impairment in a setting outside the home.
- •Participant has lived with the same parent(s) or guardian for greater than or equal to 6 months.
排除标准
- •Participant is required to or anticipates the need to take any prohibited medications or medications that have central nervous system (CNS) effects or have an effect on performance. Stable use of bronchodilator inhalers is not exclusionary.
- •Participant has taken another investigational product or has taken part in a clinical study within 30 days prior to the screening visit (Visit -1).
- •Participant is well-controlled on his/her current ADHD medication with acceptable tolerability.
- •Participant has a concurrent chronic or acute illness, disability, or other condition that might confound the results of safety assessments or may increase risk to the participant..
- •Participant has glaucoma.
- •Participant has failed to fully respond to an adequate course of amphetamine therapy.
- •Participant has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
- •Participant has a known family history of sudden cardiac death or ventricular arrhythmia.
- •Participant has a blood pressure measurement greater than or equal to 95th percentile for age, sex, and height at the screening visit (Visit -1) or the baseline visit (Visit 0) or history of moderate or severe hypertension.
- •Participant has a known history of symptomatic cardiovascular disease, unexplained syncope, exertional chest pain,advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems.
- •Participant has any clinically significant clinical laboratory abnormalities at the screening visit (Visit -1) or electrocardiogram (ECG) at screening visit (Visit-1) or baseline visit (Visit 0) based on investigator judgment.
- •Participant has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4) at the screening visit (Visit -1). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
- •Participant has a current, controlled (requiring medication or therapy) or uncontrolled, co-morbid psychiatric disorder including but not limited to any of the below co-morbid Axis I disorders and Axis II disorders:
- •i. post-traumatic stress disorder or adjustment disorder ii. bipolar illness, psychosis, or a family history of these disorders iii. pervasive developmental disorder iv. obsessive-compulsive disorder (OCD) v. psychosis/schizophrenia vi. a serious tic disorder, or a family history of Tourette's disorder vii. Participant is currently considered a suicide risk in the opinion of the investigator, has previously made a suicide attempt, or has a prior history of, or is currently demonstrating active suicidal ideation.
- •viii. a history of physical, sexual, or emotional abuse ix. any other disorder or agitated state that in the opinion of the investigator, contraindicates SPD489 or lisdexamfetamine dimesylate treatment or confound efficacy or safety assessments.
- •Participant has initiated behavioral therapy within 1 month of the baseline visit (Visit 0). Participant may not initiate behavioral therapy during the study.
- •Participant has a height less than equal to (<=) 5th percentile for age and sex at the screening visit (Visit -1).
- •Participant has a weight <= 5th percentile for age and sex at the screening visit (Visit -1).
- •Participant lives with anyone who currently abuses stimulants or cocaine.
- •Participant has a history of seizures (other than infantile febrile seizures).
- •Participant is taking any medication that is excluded per the protocol.
研究组 & 干预措施
Placebo
Participant will receive placebo matching to SPD489 (Lisdexamfetamine dimesylate) capsule for 6 weeks.
干预措施: Placebo (Drug)
SPD489 (Lisdexamfetamine dimesylate)
Participants will be randomized to receive SPD489 capsule in a 5:5:5:5:6 ratio to SPD489 5, 10, 20, 30 milligram (mg) orally once daily for 6 weeks. Dosing will begin with the lowest strength of SPD489 (5 mg), and will be titrated until the randomly assigned fixed-dose is reached.
干预措施: SPD489 (Lisdexamfetamine dimesylate) (Drug)
SPD489 (Lisdexamfetamine dimesylate)
Participants will be randomized to receive SPD489 capsule in a 5:5:5:5:6 ratio to SPD489 5, 10, 20, 30 milligram (mg) orally once daily for 6 weeks. Dosing will begin with the lowest strength of SPD489 (5 mg), and will be titrated until the randomly assigned fixed-dose is reached.
干预措施: SPD489 (Drug)
结局指标
主要结局
Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6
时间窗: Baseline, Week 6
ADHD-RS-IV Preschool Version was adapted from the ADHD Rating Scale-IV and provided examples appropriate for the developmental level of preschool children. The ADHD-RS-IV Preschool Version was an 18-item questionnaire that required the respondent to rate the frequency of occurrence of ADHD symptoms as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria. Each item was scored on a 4-point scale ranging from 0 (never or rarely) to 3 (very often) with total scores ranging from 0-54. The 18 items were grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17). Full analysis set (FAS) consisted of all participants in the safety analysis set who had at least 1 post-dose ADHD RS IV preschool version total score assessment.
次要结局
- Clinical Global Impressions Global Improvement (CGI-I) at Week 6(Week 6)
- Dose Response Relationship for Change From Baseline in ADHD-RS-IV Preschool Version Total Score in Preschool Children at Week 6(Baseline, Week 6)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From start of study drug administration up to follow-up (Week 7))
- Number of Participants With Potentially Clinically Significant Changes in Vital Signs(Week 6)
- Change From Baseline in Height at Week 6(Baseline, Week 6)
- Change From Baseline in Body Weight at Week 6(Baseline, Week 6)
- Change From Baseline in Body Mass Index (BMI) at Week 6(Baseline, Week 6)
- Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values(Week 6)
- Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters(Week 6)
- Children's Sleep Habits Questionnaire (CSHQ) at Week 6(Week 6)
- Number of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS)(Up to Week 6)