Duration and Efficacy of Azstarys on Adult ADHD Symptoms and Executive Function in Early Evening

Phase 4

Completed

Conditions: Adult Attention Deficit Hyperactivity Disorder

Interventions: Drug: Serdexmethylphenidate/dexmethylphenidate

Registration Number: NCT06000501

Lead Sponsor: NYU Langone Health

Brief Summary: This is a single-site study. One purpose of this trial is to extend the safety and efficacy evidence basis for Azstarys in adults with ADHD. This open-label, treatment study will examine the efficacy of Azstarys on ADHD symptoms using the AISRS 18-item total score on the AISRS-expanded; the Adult ADHD Investigator Symptom Rating Scale. The investigators will also examine Executive Function later in the day (early evening, about 12 hours after first morning dosing).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Adults ages 18-60 years, inclusive at the time of consent
Able to provide signed informed consent
Any gender
Subjects with a current primary DSM-5 diagnosis of ADHD of predominantly inattentive presentation, or combined presentations) as confirmed by the Adult ADHD Clinical Diagnostic Scale (ACDS) Version 1.2.5, Subjects who are not receiving any pharmacological treatment for ADHD must have an AISRS 18 item total score of AISRS expanded of ≥ 28 at screening. Subjects who were previously receiving pharmacological treatment for ADHD at screening must have a minimum total AISRS 18 item of AISRS EXPANDED score of ≥ 22 at screening
Dysthymia and anxiety disorders in remission but stable on psychiatric medication for three weeks or more at the discretion of principal investigator will be allowed- medication for these disorders to remain constant for the duration of the protocol.
Subjects who are stimulant naïve.

Exclusion Criteria

Known hypersensitivity to serdexmethylphenidate, methylphenidate, or product components.
Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days.
Lifetime bipolar disorder, psychotic disorders, autism, intellectual disability except mood disorders accepted under the inclusion criteria at the discretion of the principal investigator.
Active suicidality within past year, or history of suicide attempt in past 2 years
Any history of severe past drug dependence determined by the MINI (i.e., a focus of clinical attention or a cause of substantial social or occupational difficulty)
Concurrent substance abuse and/or history of substance use within 6 months
Use of any prescribed benzodiazepine
Any unstable medical or neurological condition; clinically significant medical abnormalities such as cardiovascular abnormalities, and any chronic condition of the central nervous system.
Any psychotropic medication usage
Known nonresponse to MPH treatment
History of allergic reaction or sensitivity to MPH
Female of childbearing age, who are breastfeeding, pregnant, planning to be pregnant or men planning to make a woman pregnant during the study or for one-month post study
PI/clinician discretion

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adult ADHD Patients	Serdexmethylphenidate/dexmethylphenidate	Enrolled participants will begin with a two-week observation stabilization before starting treatment with Azstarys. Participants found to have ≥30% change in their total Adult ADHD Investigator Symptom Rating Scale (AISRS) scores during the two-week observation stabilization period treatment will be discontinued from the study. Remaining participants will be dispensed a three-week supply of Azstarys on a weekly basis.

Primary Outcome Measures

Name	Time	Method
Change in Expanded Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score	Week 2, Week 5	The expanded AISRS is an 34-item questionnaire assessing symptoms of adult ADHD. Items are ranked on a 4-point Likert scale ranging from 0 (none) to 3 (severe). The total score is the sum of responses and ranges from 0 to 102; higher scores indicate more severe symptoms of ADHD.

Secondary Outcome Measures

Name	Time	Method
Change in Expanded AISRS - Overall Inattentive (IA) Subscale Score	Week 2, Week 5	The expanded AISRS is an 34-item questionnaire assessing symptoms of adult ADHD. The 9-item subscale of the AISRS assessing inattentive symptoms of ADHD. Items are ranked on a 4-point Likert scale ranging from 0 (none) to 3 (severe). The total score is the sum of responses and ranges from 0 to 27; higher scores indicate greater overall inattentive symptoms.
Change in Expanded AISRS - Hyperactive/Impulsive (HI) Subscale Score	Week 2, Week 5	The expanded AISRS is an 34-item questionnaire assessing symptoms of adult ADHD. The 9-item subscale of the AISRS assessing hyperactive/impulsive symptoms of ADHD. Items are ranked on a 4-point Likert scale ranging from 0 (none) to 3 (severe). The total score is the sum of responses and ranges from 0 to 27; higher scores indicate greater hyperactive/impulsive symptoms.
Change in Expanded AISRS - Overall Executive Dysfunction (EFD) Subscale Score	Week 2, Week 5	The expanded AISRS is an 34-item questionnaire assessing symptoms of adult ADHD. The 9-item subscale of the AISRS assessing executive dysfunction symptoms of ADHD. Items are ranked on a 4-point Likert scale ranging from 0 (none) to 3 (severe). The total score is the sum of responses and ranges from 0 to 27; higher scores indicate greater hyperactive/impulsive symptoms.
Change in Expanded AISRS - Overall Emotional Control (EC) Subscale Score	Week 2, Week 5	The expanded AISRS is an 34-item questionnaire assessing symptoms of adult ADHD. The 9-item subscale of the AISRS assessing emotional control symptoms of ADHD. Items are ranked on a 4-point Likert scale ranging from 0 (none) to 3 (severe). The total score is the sum of responses and ranges from 0 to 27; higher scores indicate greater hyperactive/impulsive symptoms.
Change in Adult ADHD Self Report Scale (ASRS) Symptom Checklist DSM-5 Expanded Score	Week 2, Week 5	The ASRS is a 31-item questionnaire that assesses the frequency of ADHD symptoms over the past 7 days. Items are rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The ASRS includes several subscales: an Inattentive (IA) subscale (n = 9), a Hyperactive-Impulsive (HI) subscale (n = 9), an Executive Function Deficits (EFD) subscale (n = 9), and an Emotional Dyscontrol (ED) subscale (n = 4). It also yields a total combined ADHD symptom score. The total score is calculated as the sum of all item responses and ranges from 0 to 124, with higher scores indicating greater frequency of ADHD symptoms.
Change in Adult ADHD Self Report Scale (ASRS) Symptom Checklist Hyperactive (HI) Subscale Score	Week 2, Week 5	The ASRS is a 31-item questionnaire that assesses the frequency of ADHD symptoms over the past 7 days. Items are rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The ASRS includes several subscales: an Inattentive (IA) subscale (n = 9), a Hyperactive-Impulsive (HI) subscale (n = 9), an Executive Function Deficits (EFD) subscale (n = 9), and an Emotional Dyscontrol (ED) subscale (n = 4). It also yields a total combined ADHD symptom score. The HI score ranges from 0-36. Higher scores indicating greater symptom severity.
Change in Adult ADHD Self Report Scale (ASRS) Symptom Checklist Executive Dysfunction (EFD) Subscale Score	Week 2, Week 5	The ASRS is a 31-item questionnaire that assesses the frequency of ADHD symptoms over the past 7 days. Items are rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The ASRS includes several subscales: an Inattentive (IA) subscale (n = 9), a Hyperactive-Impulsive (HI) subscale (n = 9), an Executive Function Deficits (EFD) subscale (n = 9), and an Emotional Dyscontrol (ED) subscale (n = 4). It also yields a total combined ADHD symptom score. The EFD score ranges from 0-36. Higher scores indicating greater symptom severity.symptoms.
Adult ADHD Medication Smoothness of Effect Scale (AMSES) - 8-Hour Post Dose Score	Week 5	AMSES is used to assess the smoothness of effect of ADHD medication at specified timepoints throughout the day (4, 6, 8, 10, and 12 hours after dosing). At each timepoint, participants are asked to rate whether the medication's effect feels the same as when they first took it in the morning, using a 5-point Likert scale ranging from 0 (never) to 4 (very often). Higher scores indicate greater smoothness of medication effect.
Change in Adult ADHD Self Report Scale (ASRS) Symptom Checklist Inattentive (IA) Subscale Score	Week 2, Week 5	The ASRS is a 31-item questionnaire that assesses the frequency of ADHD symptoms over the past 7 days. Items are rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The ASRS includes several subscales: an Inattentive (IA) subscale (n = 9), a Hyperactive-Impulsive (HI) subscale (n = 9), an Executive Function Deficits (EFD) subscale (n = 9), and an Emotional Dyscontrol (ED) subscale (n = 4). It also yields a total combined ADHD symptom score. The IA score ranges from 0-36. Higher scores indicating greater symptom severity.
Change in Adult ADHD Self Report Scale (ASRS) Symptom Checklist Score Overall Emotional Dyscontrol (ED) Subscale Score	Week 2, Week 5	The ASRS is a 31-item questionnaire that assesses the frequency of ADHD symptoms over the past 7 days. Items are rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The ASRS includes several subscales: an Inattentive (IA) subscale (n = 9), a Hyperactive-Impulsive (HI) subscale (n = 9), an Executive Function Deficits (EFD) subscale (n = 9), and an Emotional Dyscontrol (ED) subscale (n = 4). It also yields a total combined ADHD symptom score. The ED score ranges from 0-36. Higher scores indicating greater symptom severity.
Change in 4-Hour Post-Dose TASS Score	Week 2, Week 5	18-item assessment of ADHD symptoms. Each item is rated on a 4-point Likert scale from 0 (not at all) to 3 (severe). The total score is the sum of responses and ranges from 0 to 54; higher scores indicate greater severity of symptoms.
Change in 1-Hour Post-Dose Time-Sensitive ADHD Symptom Scale (TASS) Score	Week 2, Week 5	18-item assessment of ADHD symptoms. Each item is rated on a 4-point Likert scale from 0 (not at all) to 3 (severe). The total score is the sum of responses and ranges from 0 to 54; higher scores indicate greater severity of symptoms.
Adult ADHD Medication Smoothness of Effect Scale (AMSES) - 6-Hour Post Dose Score	Week 5	AMSES is used to assess the smoothness of effect of ADHD medication at specified timepoints throughout the day (4, 6, 8, 10, and 12 hours after dosing). At each timepoint, participants are asked to rate whether the medication's effect feels the same as when they first took it in the morning, using a 5-point Likert scale ranging from 0 (never) to 4 (very often). Higher scores indicate greater smoothness of medication effect.
Adult ADHD Medication Smoothness of Effect Scale (AMSES) - 10-Hour Post Dose Score	Week 5	AMSES is used to assess the smoothness of effect of ADHD medication at specified timepoints throughout the day (4, 6, 8, 10, and 12 hours after dosing). At each timepoint, participants are asked to rate whether the medication's effect feels the same as when they first took it in the morning, using a 5-point Likert scale ranging from 0 (never) to 4 (very often). Higher scores indicate greater smoothness of medication effect.
Change in 12-Hour Post-Dose TASS Score	Week 2, Week 5	18-item assessment of ADHD symptoms. Each item is rated on a 4-point Likert scale from 0 (not at all) to 3 (severe). The total score is the sum of responses and ranges from 0 to 54; higher scores indicate greater severity of symptoms.
Adult ADHD Medication Smoothness of Effect Scale (AMSES) - 4-Hour Post Dose Score	Week 5	AMSES is used to assess the smoothness of effect of ADHD medication at specified timepoints throughout the day (4, 6, 8, 10, and 12 hours after dosing). At each timepoint, participants are asked to rate whether the medication's effect feels the same as when they first took it in the morning, using a 5-point Likert scale ranging from 0 (never) to 4 (very often). Higher scores indicate greater smoothness of medication effect.
Adult ADHD Medication Smoothness of Effect Scale (AMSES) - 12-Hour Post Dose Score	Week 5	AMSES is used to assess the smoothness of effect of ADHD medication at specified timepoints throughout the day (4, 6, 8, 10, and 12 hours after dosing). At each timepoint, participants are asked to rate whether the medication's effect feels the same as when they first took it in the morning, using a 5-point Likert scale ranging from 0 (never) to 4 (very often). Higher scores indicate greater smoothness of medication effect.
AMSES - Overall Smoothness of Effect Scale Score	Week 5	AMSES is an assessment of the smoothness of effect of ADHD medication throughout the day following dosing. The overall smoothness of effect scale is a subscale part of the AMSES that asks participants to respond to "How smooth do you think your medication effect is throughout the day?" on a scale from 0 (never) to 100 (very often). The higher the score, the smoother the medication effect is throughout the day.
Change in Behavioral Regulation Index (BRI) T-Score	Week 2, Week 5	The Behavioral Regulation Index (BRI) t-score on the BRIEF-A (Behavior Rating Inventory of Executive Function-Adult Version) is a summary measure of an individual's ability to regulate their behavior and emotions, 50 indicates the population mean with a standard deviation of 10. A t-score of 65 or higher indicates difficulties in behavioral regulation.
Change in Metacognition Index (MI) T-Score	Week 2, Week 5	The Metacognition Index (MI) t-score on the BRIEF-A (Behavior Rating Inventory of Executive Function-Adult Version) is a measure of executive function that assesses an individual's ability to initiate, plan, organize, self-monitor, and manage their own cognitive processes, 50 indicates the population mean with a standard deviation of 10. A t-score of 65 or higher indicates difficulties with executive function related to planning, organization, and cognitive self-regulation.
Change in Global Executive Composite (GEC) T-score	Week 2, Week 5	The Global Executive Composite (GEC) t-score on the BRIEF-A (Behavior Rating Inventory of Executive Function-Adult Version) is a summary measure of overall executive function, 50 indicates the population mean with a standard deviation of 10. A t-score of 65 or higher indicates difficulties with executive function in daily life.
Change in Clinical Global Impression-Severity (CGI-S) Scale Score	Week 2, Week 5	1-item clinician-rated assessment of the severity of a subject's mental illness. The severity of illness is rated as follows: 0 (not assessed), 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill subjects). The total score is the numerical ranking provided by the clinician.