A Phase 4, Open-Label, Multicentre, Safety Study of Lisdexamfetamine Dimesylate in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 314
- 试验地点
- 35
- 主要终点
- Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Last On-treatment Assessment (LOTA)
研究概览
简要总结
While the Lisdexamfetamine Dimesylate (SPD489) clinical program has studied the efficacy, safety, and tolerability of SPD489 in treating core symptoms of ADHD in children and adolescents aged 6-17 years and adults aged 18-55 years, the majority of these studies have been of short duration - up to 8 weeks.
A number of long-term studies have been undertaken (up to 1 year) and these have confirmed the safety and ongoing efficacy in this patient population.
In order to run a study with investigational medication within Poland the study changed to a Phase 3 rather than a Phase 4 study in that country. Please note that the study number remains as SPD489-404.
Study SPD489-404 has been designed to further evaluate the long-term effects of SPD489 in children and adolescents over a 2-year treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
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
- •For subjects who participated in another SPD489 study (SPD489-317, SPD489-325, or SPD489 326):
- •Subject is a male or female aged 6-17 years.
- •Subject participated in SPD489-317, completed 9 weeks of treatment, and completed the 1 week post-treatment safety follow-up visit.
- •For subjects who have not participated in another SPD489 study:
- •Subject is a male or female aged 6-17 years.
- •Subject must meet DSM-IV-TR criteria for a primary diagnosis of ADHD based on a detailed psychiatric evaluation.
- •For all subjects:
- •Subject has a Baseline ADHD-RS-IV total score greater than or equal to
- •Subject, who is female of childbearing potential (FOCP), must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test, and a negative urine pregnancy test at Baseline, be non-lactating and agree to comply with any applicable contraceptive requirements of the protocol.
- •Subject and parent/LAR are willing and able to comply with all the testing and requirements defined, including oversight of morning dosing. Specifically, the parent/LAR must be available upon awakening, at approximately 7:00 AM, to dispense the dose of Investigational Product for the duration of the study.
- •Subject aged greater than or equal to 18 years has a systolic blood pressure less than or equal to 139 mmHg and a diastolic blood pressure less than or equal to 89 mmHg.
- •Subject is able to swallow a capsule.
排除标准
- •For subjects who participated in another SPD489 study (SPD489-317, SPD489-325, or SPD489 326):
- •Subject was terminated from a previous SPD489 study (SPD489-325 or SPD489 326) for protocol non-adherence and/or subject non-compliance and/or experienced a medication-related SAE or AE resulting in termination from the previous study.
- •Subject experienced any clinically significant AEs in a prior SPD489 study (SPD489 317, SPD489-325, or SPD489-326) that, in the opinion of the Investigator, would preclude further exposure to SPD
- •For all subjects:
- •Subject's symptoms are well-controlled on their currently prescribed ADHD medication with acceptable tolerability.
- •Subject has a positive urine drug result at Screening.
- •Subject has a current, controlled (requiring a restricted medication) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as any severe comorbid Axis II disorder or severe Axis I disorder (such as Post Traumatic Stress Disorder, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder) or other symptomatic manifestations, such as agitated states, marked anxiety, or tension.
- •Subject has taken another Investigational Product or taken part in a clinical study with the exception of a prior SPD489 study (SPD489-317, SPD489 325, or SPD489 326) within 30 days prior to Screening.
- •Subject weighs less than 22.7 kg (50 lbs).
- •Subject is significantly overweight.
- •Subject has a conduct disorder. Oppositional defiant disorder is not exclusionary.
- •Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments conducted in the study or that might increase risk to the subject.
- •Subject 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. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the Investigator
- •Subject has glaucoma.
- •Subject has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
- •Subject has any clinically significant ECG abnormality.
- •Subject has any clinically significant laboratory abnormalities.
- •Subject has a documented allergy, hypersensitivity, or intolerance to any active ingredient or excipients in SPD
- •Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine) in accordance with DSM-IV-TR criteria.
- •Subject has a history of seizures (other than infantile febrile seizures), a chronic or current tic disorder, a current diagnosis of Tourette's Disorder, or a known family history of Tourette's Disorder. Subject has a history of tics that is judged by the Investigator to be exclusionary.
- •Subject has a known history of symptomatic cardiovascular or cerebrovascular 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.
- •Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
- •Subject has a medical condition, other than ADHD, that requires treatment with medications that have central nervous system effects and/or affect performance. Stable use of anticholinergic or theophylline bronchodilators is not exclusionary.
研究组 & 干预措施
Lisdexamfetamine Dimesylate
干预措施: Lisdexamfetamine dimesylate (Drug)
结局指标
主要结局
Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
Change From Baseline in Body Weight at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
Number of Participants With All Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
时间窗: Baseline up to 3 days after the last dose of study treatment (up to 2 years)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. It included both serious and non-serious adverse event. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs were defined as treatment-emergent if they started or worsened during the period between the day of a participant's first dose of investigational product in this study and the 3 days following cessation of treatment.
Change From Baseline in Pulse Rate at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
Change From Baseline in Height at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
Change From Baseline in QT Interval at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
Change From Baseline in Heart Rate at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
Change From Baseline in Body Mass Index (BMI) at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
BMI was calculated as (weight \[kilogram\] per height \[square meter\]).
Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRSC) Total Scores at Last On-treatment Assessment (LOTA)
时间窗: Baseline (Week 0), LOTA (Week 104)
The BPRS-C that was designed to provide a characterization of the child and adolescent psychopathology, was used to monitor participant's safety. The BPRS-C assessed 7 independent factors (3 items each), for a total of 21 items that represented behavioural disorders, depression, thinking disturbance, psychomotor excitation, withdrawal retardation, anxiety, and organicity. Each item was rated using a 7-point scale including 0 (not present), 1 (very mild), 2 (mild), 3 (moderate), 4 (moderately severe), 5 (severe), and 6 (extremely severe). Total score is the sum of each item score; range from 0 to 126. Higher score indicated worse psychology.
次要结局
- Number of Participants With Clinical Global Impression-Severity of Illness (CGI-S) at Last On-treatment Assessment (LOTA)(LOTA (Week 104))
- Number of Participants With Clinical Global Impression-Global Improvement (CGI-I) at Last On-treatment Assessment (LOTA)(LOTA (Week 104))
- Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Total Score at Last On-treatment Assessment (LOTA)(Baseline (Week 0), LOTA (Week 104))