Evaluation of Foquest in Adults 65 Years and Older With ADHD

Phase 4Not Yet RecruitingNCT07710014

Dar Clinical Research Inc.36 enrolled

Overview

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.

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. Secondary Endpoints: Change from baseline to Week 8 in ASRS-5 total score, CGI-S score, BRIEF-A Global Executive Composite T-score, and distribution of CGI-I scores at Week 8. Cardiovascular parameters (systolic and diastolic blood pressure, heart rate, QTcF interval) and adverse events will be analyzed as safety endpoints. Sample Size: 36 participants are planned, allowing for up to 15% attrition to ensure 30 completers, providing 80% power to detect a within-subject effect size of Cohen's d of 0.53 or greater. This study addresses a critical evidence gap regarding the pharmacological treatment of ADHD in older adults and aims to inform evidence-based prescribing decisions for this underserved population.

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female aged 65 years or older at the time of consent. 2. Mentally and physically competent to provide informed consent and willing to comply with the study protocol 3. Meets DSM-5 criteria for ADHD combined presentation, inattentive presentation, or hyperactive/impulsive presentation based on clinical history 4. SRS-5 score of 14 or greater at screening 5. AISRS total score of 24 or greater at baseline 6. Montreal Cognitive Assessment (MoCA) score of 26 or greater Exclusion Criteria: 1. Satisfied with current ADHD treatment 2. History of myocardial infarction, arrhythmia, or congenital heart disease 3. Mean systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg measured in triplicate at screening despite treatment 4. Treated hypertension not stable on medication or with dose changes in the last 30 days 5. History of transient ischemic attack or stroke 6. Current or lifetime DSM-5 diagnosis of bipolar I or II disorder, cyclothymic disorder, or bipolar disorder not otherwise specified 7. Clinical history strongly suggestive of undiagnosed bipolar spectrum disorder 8. Active suicidal ideation or behavior per C-SSRS at screening 9. Current substance use disorder 10. History of drug or alcohol abuse in the last 10 years as defined by DSM-5 criteria for substance use disorder (moderate or severe) 11. True allergy to methylphenidate, history of serious adverse reactions to methylphenidate, or known non-response to methylphenidate 12. History of seizure disorder other than a single childhood febrile seizure before age 3 13. History of glaucoma, hyperthyroidism, thyrotoxicosis, advanced arteriosclerosis, or severe renal insufficiency (eGFR less than 30 mL/min/1.73 m²) 14. Use of a monoamine oxidase inhibitor currently or within the past 14 days 15. Abnormal baseline ECG including left ventricular hypertrophy or QTc greater than 450 ms (males) or greater than 470 ms (females) 16. History of heart failure, unexplained dyspnea on exertion, or newly identified murmur 17. MoCA score less than 26 or evidence of cognitive impairment 18. Currently considered a suicide risk in the opinion of the investigator

Outcomes

Primary Outcomes

Mean Change in Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score

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.

Time frame: Baseline (Week 1) to End of Treatment (Week 8)

Secondary Outcomes

Mean Change in ASRS-5 Total Score

Mean change from baseline to Week 8 in the Adult ADHD Self-Report Scale version 1.1 (ASRS-5) total score. The ASRS-5 is an 18-item self-report questionnaire with Part A (Inattention) and Part B (Hyperactivity/Impulsivity), items rated 0 (Never) to 4 (Very Often). Analyzed using paired t-test and repeated-measures ANOVA across post-baseline timepoints (Weeks 3, 5, and 8).

Time frame: Baseline (Week 1) to Week 8, with interim assessments at Weeks 3 and 5

Mean Change in Clinical Global Impression - Severity (CGI-S) Score

Mean change from baseline to Week 8 in CGI-S score. The CGI-S is a 7-point clinician-rated scale of overall illness severity (1 = Normal, not at all ill; 7 = Among the most extremely ill patients). A responder analysis will report the proportion of participants achieving CGI-S score of 3 or less (mildly ill or better) at Week 8.

Time frame: Baseline (Week 1) to Week 8

Clinical Global Impression - Improvement (CGI-I) Responder Rate

Distribution of CGI-I scores at Week 8. The CGI-I is a 7-point clinician-rated scale evaluating change from baseline (1 = Very much improved; 7 = Very much worse). The clinical responder rate is defined as the proportion of participants rated as much improved or very much improved (CGI-I score of 2 or less) at Week 8, reported with 95% exact binomial confidence intervals.

Time frame: Week 8 (End of Treatment)

Mean Change in BRIEF-A Global Executive Composite (GEC) T-Score

Mean change from baseline to Week 8 in the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Global Executive Composite T-score. The BRIEF-A is a 75-item self-report measure of executive functioning in adults aged 18-90, producing norm-referenced T-scores. Higher scores indicate greater executive dysfunction. Individual index scores (Behavioral Regulation Index, Metacognition Index) will also be analyzed.

Time frame: Baseline (Week 1) to Week 8

Change in Systolic Blood Pressure

Mean change from baseline to Week 8 in resting systolic blood pressure (mmHg). Assessed at in-person visits at Weeks 0, 3, 5, and 8. Outlier criteria: systolic BP greater than 140 mmHg or increase greater than 20 mmHg from baseline.

Time frame: Baseline (Week 1) to Week 8, with interim assessments at Weeks 3 and 5

Incidence of Treatment-Emergent Adverse Events

Incidence of treatment-emergent adverse events (TEAEs) summarized by system organ class and preferred term using MedDRA coding. TEAEs tabulated by severity (mild, moderate, severe) and relationship to study medication. Serious adverse events, adverse events leading to dose modification, and adverse events leading to discontinuation reported separately.

Time frame: From first dose of study medication to 14 days after study completion (approximately 10 weeks)

Columbia-Suicide Severity Rating Scale (C-SSRS) Changes

C-SSRS data summarized at each visit using frequency and percentage of participants in each suicidal ideation severity category (0-5), shift tables showing treatment-emergent changes from baseline (new onset or worsening of suicidal ideation category), and incidence of any suicidal behavior events.

Time frame: Baseline (Week 1) through End of Study/Follow-Up (Week 10), assessed at every study visit

Evaluation of Foquest in Adults 65 Years and Older With ADHD

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts