Evaluation of Foquest® (Multilayer-Release Methylphenidate) in Adults ≥ 65 Years With ADHD: An Open-Label, Investigator-Initiated Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 36
- 主要终点
- Mean Change in Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score
研究概览
简要总结
This study is evaluating the safety and effectiveness of Foquest (multilayer-release methylphenidate), a once-daily extended-release medication for attention-deficit/hyperactivity disorder (ADHD), in adults aged 65 years and older.
ADHD can persist into older age and is associated with reduced quality of life and difficulties with executive function. Foquest is currently approved in Canada for the treatment of ADHD in adults up to age 65, but there is very limited research on its use in older adults. People over 65 may respond differently to stimulant medications due to age-related changes in how the body processes drugs, other medical conditions, and increased sensitivity to cardiovascular side effects.
This is an open-label study, meaning all participants will know they are receiving the study medication. There is no placebo group. Participants will take Foquest once daily for approximately 10 weeks, including a 6-week dose adjustment period, a 2-week maintenance period, and a 2-week follow-up period. The dose will start at 25 mg daily and may be increased weekly up to a maximum of 100 mg daily based on how well the participant responds and tolerates the medication.
The main goal of the study is to measure changes in ADHD symptoms using a clinician-rated scale called the Adult ADHD Investigator Symptom Rating Scale (AISRS). The study will also assess changes in executive function, overall clinical improvement, and cardiovascular safety measures including blood pressure, heart rate, and electrocardiograms (ECGs). Safety will be closely monitored throughout the study, with enhanced cardiovascular monitoring during the first 6 weeks of treatment.
详细描述
This is a prospective, open-label, within-subject (pre-post), investigator-initiated Phase IV trial evaluating the safety and efficacy of Foquest (multilayer-release methylphenidate hydrochloride; MLR-MPH) in adults aged 65 years and older with a DSM-5 diagnosis of ADHD.
Background: Foquest is a once-daily oral stimulant consisting of a 20% immediate-release outer layer and an 80% delayed-release core, with onset of effect within approximately 1 hour and duration of up to 16 hours. It is approved by Health Canada for ADHD in adults up to age 65. The product monograph acknowledges that data are lacking for individuals above this age. Pharmacoepidemiologic evidence (Tadrous et al., 2021) suggests a transient increase in cardiovascular risk during the first 30 days of stimulant initiation in adults aged 66 and older, underscoring the need for careful cardiac screening and monitoring in this population.
Study Design: Each participant will be involved for approximately 10 weeks, comprising a 6-week dose titration phase, a 2-week maintenance phase, and a 2-week follow-up period. Participants will attend 5 in-person visits and 4 phone visits. Foquest will be initiated at 25 mg daily (or an investigator-selected dose based on prior medication history) and titrated weekly to a maximum of 100 mg daily based on efficacy and tolerability.
Cardiovascular Safety Monitoring: Enhanced cardiovascular monitoring is incorporated based on published evidence of early cardiovascular risk with stimulant initiation in older adults. Blood pressure and heart rate are measured in triplicate at screening and assessed at all in-person visits. Twelve-lead ECGs are performed at screening, baseline, Week 3, Week 5, and end of treatment (Week 8). Predefined criteria for treatment interruption include sustained resting heart rate greater than 100 bpm, systolic blood pressure greater than 180 mmHg, or diastolic blood pressure greater than 110 mmHg. Immediate discontinuation criteria include blood pressure at or above 180/120 mmHg, new arrhythmia, or symptoms suggestive of acute cardiovascular or cerebrovascular events.
Primary Endpoint: Mean change from baseline (Week 1) to end of treatment (Week 8) in AISRS total score, analyzed using a paired t-test in the modified intention-to-treat population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 65 years or older at the time of consent.
- •Mentally and physically competent to provide informed consent and willing to comply with the study protocol
- •Meets DSM-5 criteria for ADHD combined presentation, inattentive presentation, or hyperactive/impulsive presentation based on clinical history
- •SRS-5 score of 14 or greater at screening
- •AISRS total score of 24 or greater at baseline
- •Montreal Cognitive Assessment (MoCA) score of 26 or greater
排除标准
- •Satisfied with current ADHD treatment
- •History of myocardial infarction, arrhythmia, or congenital heart disease
- •Mean systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg measured in triplicate at screening despite treatment
- •Treated hypertension not stable on medication or with dose changes in the last 30 days
- •History of transient ischemic attack or stroke
- •Current or lifetime DSM-5 diagnosis of bipolar I or II disorder, cyclothymic disorder, or bipolar disorder not otherwise specified
- •Clinical history strongly suggestive of undiagnosed bipolar spectrum disorder
- •Active suicidal ideation or behavior per C-SSRS at screening
- •Current substance use disorder
- •History of drug or alcohol abuse in the last 10 years as defined by DSM-5 criteria for substance use disorder (moderate or severe)
- •True allergy to methylphenidate, history of serious adverse reactions to methylphenidate, or known non-response to methylphenidate
- •History of seizure disorder other than a single childhood febrile seizure before age 3
- •History of glaucoma, hyperthyroidism, thyrotoxicosis, advanced arteriosclerosis, or severe renal insufficiency (eGFR less than 30 mL/min/1.73 m²)
- •Use of a monoamine oxidase inhibitor currently or within the past 14 days
- •Abnormal baseline ECG including left ventricular hypertrophy or QTc greater than 450 ms (males) or greater than 470 ms (females)
- •History of heart failure, unexplained dyspnea on exertion, or newly identified murmur
- •MoCA score less than 26 or evidence of cognitive impairment
- •Currently considered a suicide risk in the opinion of the investigator
结局指标
主要结局
Mean Change in Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score
时间窗: Baseline (Week 1) to End of Treatment (Week 8)
Mean change from baseline (Week 1) to end of treatment (Week 8) in AISRS total score. The AISRS is an 18-item clinician-administered scale aligned with DSM criteria for ADHD, with each item rated 0-3 (total score range 0-54). Higher scores indicate greater symptom severity. Analysis uses a paired t-test in the modified intention-to-treat population.
次要结局
- Mean Change in ASRS-5 Total Score(Baseline (Week 1) to Week 8, with interim assessments at Weeks 3 and 5)
- Mean Change in Clinical Global Impression - Severity (CGI-S) Score(Baseline (Week 1) to Week 8)
- Clinical Global Impression - Improvement (CGI-I) Responder Rate(Week 8 (End of Treatment))
- Mean Change in BRIEF-A Global Executive Composite (GEC) T-Score(Baseline (Week 1) to Week 8)
- Change in Systolic Blood Pressure(Baseline (Week 1) to Week 8, with interim assessments at Weeks 3 and 5)
- Incidence of Treatment-Emergent Adverse Events(From first dose of study medication to 14 days after study completion (approximately 10 weeks))
- Columbia-Suicide Severity Rating Scale (C-SSRS) Changes(Baseline (Week 1) through End of Study/Follow-Up (Week 10), assessed at every study visit)