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

Study Overview
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Brief Summary
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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).

Official Title
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An Open-Label Treatment, Investigator-Initiated Study, on the Duration and Efficacy of Azstarys (Serdexmethylphenidate and Dexmethylphenidate) on Adult ADHD Symptoms and Executive Function in Early Evening

Conditions
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Adult Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Serdexmethylphenidate/dexmethylphenidate


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult ADHD Patients<br>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. | Drug: Serdexmethylphenidate/dexmethylphenidate<br>* Azstarys capsules for once-daily oral use for three weeks. Flexible dose starting at 39.2 mg serd-mph/7.8 mg d-mph and moving up to 52.3 mg serd-mph/10.4 mg d-mph.<br>* Other names: Azstarys;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Expanded Adult ADHD Investigator Symptom Rating Scale (AISRS) Score from Baseline to Week 2 | The expanded AISRS is an 18-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 54; higher scores indicate more severe symptoms of ADHD. | Baseline, Week 2 | 
| Change in Expanded AISRS Score from Baseline to Week 5 | The expanded AISRS is an 18-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 54; higher scores indicate more severe symptoms of ADHD. | Baseline, Week 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Expanded AISRS - Overall Inattentive (IA) Subscale Score | 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. | Baseline, Week 2 | 
| Change in Expanded AISRS - Overall Inattentive (IA) Subscale Score | 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. | Baseline, Week 5 | 
| Change in Expanded AISRS - Hyperactive/Impulsive (HI) Subscale Score | 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. | Baseline, Week 2 | 
| Change in Expanded AISRS - Hyperactive/Impulsive (HI) Subscale Score | 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. | Baseline, Week 5 | 
| 1-Hour Post-Dose TASS Score at Visit 3 | 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. | Week 2 (1-hour Post-Dose) | 
| 1-Hour Post-Dose TASS Score at Visit 4 | 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. | Week 3 (1-hour Post-Dose) | 
| 1-Hour Post-Dose TASS Score at Visit 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. | Week 4 (1-hour Post-Dose) | 
| 1-Hour Post-Dose TASS Score at Visit 6 | 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. | Week 5 (1-hour Post-Dose) | 
| 4-Hour Post-Dose TASS Score at Visit 3 | 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. | Week 2 (4-hours Post-Dose) | 
| 4-Hour Post-Dose TASS Score at Visit 4 | 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. | Week 3 (4-hours Post-Dose) | 
| 4-Hour Post-Dose TASS Score at Visit 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. | Week 4 (4-hours Post-Dose) | 
| 4-Hour Post-Dose TASS Score at Visit 6 | 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. | Week 5 (4-hours Post-Dose) | 
| 12-Hour Post-Dose TASS Score at Visit 3 | 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. | Week 2 (12-hours Post-Dose) | 
| 12-Hour Post-Dose TASS Score at Visit 4 | 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. | Week 3 (12-hours Post-Dose) | 
| 12-Hour Post-Dose TASS Score at Visit 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. | Week 4 (12-hours Post-Dose) | 
| 12-Hour Post-Dose TASS Score at Visit 6 | 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. | Week 5 (12-hours Post-Dose) | 
| 1-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 3 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 2 (1-hour Post-Dose) | 
| 1-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 4 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 3 (1-hour Post-Dose) | 
| 1-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 5 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 4 (1-hour Post-Dose) | 
| 4-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 3 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 2 (1-hour Post-Dose) | 
| 4-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 4 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 3 (1-hour Post-Dose) | 
| 4-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 5 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 4 (1-hour Post-Dose) | 
| 4-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 6 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 5 (1-hour Post-Dose) | 
| 12-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 3 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 2 (1-hour Post-Dose) | 
| 12-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 4 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 3 (1-hour Post-Dose) | 
| 12-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 5 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 4 (1-hour Post-Dose) | 
| 12-Hour Post-Dose Smoothness of Effect Scale (AMSES) Score at Visit 6 | 5-item assessment of the smoothness of effect of ADHD medication throughout the day following dosing. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 20; higher scores indicate greater smoothness of effect of medication. | Week 5 (1-hour Post-Dose) | 
| Change in Adult ADHD Self Report Scale (ASRS) Symptom Checklist Score | The ASRS is a 31-item questionnaire assessing frequency of ADHD symptoms over the previous 7 days. Items are rate on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 124; higher scores indicate greater frequency of ADHD symptoms. | Baseline, Week 2 | 
| Change in Adult ADHD Self Report Scale (ASRS) Symptom Checklist Score | The ASRS is a 31-item questionnaire assessing frequency of ADHD symptoms over the previous 7 days. Items are rate on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score is the sum of responses and ranges from 0 to 124; higher scores indicate greater frequency of ADHD symptoms. | Baseline, Week 5 | 
| Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Score | The BRIEF-A is a 75-item self-report questionnaire assessing behavioral issues. Items are rated on a 3-point Likert scale: 0 (never), 1 (sometimes), and 2 (often). | Baseline, Week 2 | 
| Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Score | The BRIEF-A is a 75-item self-report questionnaire assessing behavioral issues. Items are rated on a 3-point Likert scale: 0 (never), 1 (sometimes), and 2 (often). | Baseline, Week 5 | 
| Change from Baseline in Clinical Global Impression-Severity (CGI-S) Scale Score | 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. | Baseline, Week 2 | 
| Change from Baseline in Clinical Global Impression-Severity (CGI-S) Scale Score | 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. | Baseline, Week 5 |