Adult Study / OROS Methylphenidate Hydrochloride (HCL) (OROS MPH) in Adults With Attention Deficit Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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The purpose of this study is to compare the ADHD symptom response of adults with ADHD treated with OROS MPH to those treated with placebo.

Detailed Description
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The hypothesis is that Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCL (OROS MPH) is safe and effective in improving Attention Deficit Hyperactivity Disorder (ADHD) symptoms in adults with ADHD when compared to placebo as demonstrated using specific study measures. This is a double-blind (neither participant nor investigator knows the name of the assigned study drug), randomized (study drug assigned by chance), placebo-controlled study to evaluate the efficacy and safety of OROS MPH using the optimal dose for each adult patient in the study with ADHD. The primary efficacy variable in this study is the change from baseline to final evaluation using the Adult ADHD Investigator Symptom Rating Scale (AISRS) to measure patient ADHD symptoms. Participants will also be assessed for adverse events throughout the study. Patients will initiate treatment with oral OROS MPH 18 mg or matching placebo at baseline and continue morning dosing with increases every week until an optimal dose is achieved, up to the maximum of 72 mg/day of OROS MPH or matching placebo. Eligible patients will remain in the study for a maximum of 6 weeks.

Official Title
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A Placebo Controlled Double-Blind, Parallel Group, Individualizing Dosing Study Optimizing Treatment of Adults With Attention Deficit Hyperactivity Disorder to an Effective Response With OROS Methylphenidate

Conditions
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Attention Deficit Disorder With Hyperactivity

Intervention / Treatment
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* Drug: OROS MPH
* Drug: Placebo
* Drug: OROS MPH Tablets
* Drug: Placebo Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ADHD diagnosis (any type: Combined, Predominantly Inattentive, or Predominantly Hyperactive-Impulsive) Patients with an Adult ADHD Investigator Symptom Rating Scale (AISRS) score greater than 24 at screening/baseline Ability to read and understand English Exclusion Criteria: Any significant history of cardiovascular disease or cardiovascular disease detectable via ECG History of diagnosis of substance or alcohol dependence or admission/hospitalization for rehabilitation for dependence Current neurologic or psychiatric diagnosis that would make patient inappropriate for participation Anxiety assessments of moderate or severe Depression assessments of moderate or severe History or current suicidal thoughts or attempts Known allergies, hypersensitivity, or intolerance to OROS MPH

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>OROS MPH Optimal Patient Dose (18 mg-72 mg) once daily by mouth for 6 weeks | Drug: OROS MPH<br>* Optimal Patient Dose (18 mg-72 mg) once daily for 6 weeks<br>Drug: OROS MPH Tablets<br>* Optimal Patient Dose (18 mg-72 mg) once daily by mouth for 6 weeks<br>|
| Placebo Comparator: 002<br>Placebo Optimal Patient Dose (placebo to match 18 mg - 72 mg) once daily by mouth for 6 weeks | Drug: Placebo<br>* Optimal Patient Dose (placebo to match 18 mg - 72 mg) once daily for 6 weeks<br>Drug: Placebo Tablets<br>* Optimal Patient Dose (placebo to match 18 mg - 72 mg) once daily by mouth for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Score (AISRS) Over Time Using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Fourth Edition for Diagnosis | The Adult ADHD Investigator Symptom Rating Score (AISRS) assesses 18 core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms for adult subjects based on the investigator's rating for each of the symptoms using a four point scale (0=None, 1=Mild, 2=Moderate, and 3=Severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The AISRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms). | Baseline, endpoint (42 days or early discontinuation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reaction Time Domain of the Stroop Test (Cognitive and Executive Function) | Stroop Test is a computerized measure of inhibition/disinhibition, executive function, reaction time, and information processing. The 1st part generates basic reaction time to colors. The 2nd part generates complex reaction time score to matching color names and font color. The 3rd part establishes a Stroop reaction time and an error score to unmatched color names/fonts. Reaction Time Domain Score = (Stroop Complex Reaction Time Correct + Stroop Reaction Time Correct)/2. Lower scores indicate better functioning (i.e. reaction time). | Baseline, 4 hour timepoint for extended days or last non-missing value for non-extended days on day 42 or early discontinuation (endpoint) | 
| Vigilance Domain (Complex Attention) of the Stroop Test/Shifting Attention Test (SAT)/Continuous Performance Test (CPT) (Cognitive and Executive Function) | The Stroop Test is a computerized measure of inhibition/disinhibition, executive function, reaction time, and information processing. The Shifting Attention Test (SAT) a computerized measure of the ability to shift from one instruction set to another quickly and accurately. The Continuous Performance Test (CPT) is a computerized measure of vigilance or sustained attention/attention over time. Vigilance Domain (Complex Attention) Score = Stroop Commission Errors + SAT Errors + CPT Commission Errors + CPT Omission Errors. Lower scores indicate better functioning (i.e. sustained attention). | Baseline, endpoint (42 days or early discontinuation) | 
| Cognitive Flexibility Domain of the Stroop/SAT Tests (Cognitive and Executive Function) | The Stroop Test is a computerized measure of inhibition/disinhibition, executive function, reaction time, and information processing. The SAT is a computerized measure of the ability to shift from one instruction set to another quickly and accurately. The scores generated by the SAT are: correct matches, errors, and response time. The testing score is a measure of cognitive flexibility. Cognitive Flexibility Domain Score = SAT Correct Responses - SAT Errors - Stroop Commission Errors. Higher scores indicate better accuracy. | Baseline, 4 hour timepoint for extended days or last non-missing value for non-extended days on day 42 or early discontinuation (endpoint) | 
| Processing Speed Domain of the Symbol Digit Modalities Test (SDTM) (Cognitive and Executive Function) | The Symbol Digit Modalities Test (SDMT) is a computerized variant of the Wechsler Digit Symbol Substitution Test (DSST), but the position of symbols and digits is reversed. Scoring is the number of correct responses generated in 2 minutes. Processing Speed Domain = SDMT correct responses - SDMT errors. Higher scores indicate better functioning (i.e. information processing). | Baseline, endpoint (42 days or early discontinuation) | 
| Global Executive Composite (GEC) Score of the Brief Rating Inventory of Executive Function for Adults (BRIEF-A) | The BRIEF-A is a self-reported measure (low=61, high=225, lower scores indicate higher executive functioning) capturing views of the subject's own functioning in the everyday environment. The BRIEF-A contains 75 scored items (1=never, 2=sometimes, 3=often) in 9 non-overlapping clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). The Behavioral Regulation Index (BRI), Metacognition Index (MI), and GEC are then derived. | Baseline, endpoint (42 days or early discontinuation) | 
| Performance and Daily Functioning Scale of the Adult ADHD Impact Module (AIM-A) | The AIM-A is a subject-reported measure (low=0, high=100, a higher score is more favorable) to assess the overall impact and role that ADHD may have in the conduct of tasks that are expected of adults. The AIM-A is comprised of four global quality of life items, five economic impact items, and five multi-item scales that describe important concepts. Items include: Living with ADHD; General Well-Being; Work, Home and School Performance and Daily Functioning; Relationships; and Communication; and Impact of Symptoms (emotional, degree of daily interference). | Baseline, endpoint (42 days or early discontinuation) | 
| Subject's Rating of Endicott Work Productivity Scale (EWPS) | The EWPS provides a measure of the subject's report of their overall productivity (low=0, high=100, a higher score indicates worsening work productivity and efficiency). There are 25 items (questions 15-39) on the scale that describe types of behaviors/ subjective feelings that are highly likely to reduce work productivity/efficiency. These 25 items are rated on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=often, to 4=almost always) indicating how often the behavior, feeling or attitude has been manifested in the past week. The total score is the sum of the 25 items. | Baseline, endpoint (42 days or early discontinuation) | 
| Subject's Rating of Dyadic Satisfaction Subscale (DSS) | The Dyadic Adjustment Scale (DAS) assesses the relationship satisfaction or adjustment of partners in committed couple relationships. The 32-question DAS includes 4 empirically validated subscales that measure: dyadic satisfaction, dyadic consensus, dyadic cohesion and affectional expression. The response format varies across the entire scale and includes 5-, 6-, and 7-point Likert-scale questions and two yes/no items. The 10-question subset of the DAS, the Dyadic Satisfaction Subscale, was used in this study (low=0, high=50, higher score means better relationship satisfaction). | Baseline, endpoint (42 days or early discontinuation) | 
| Subject's Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication You Are Taking for ADHD? | The satisfaction with treatment questionnaire (low=0, high=20, a lower score indicates lower satisfaction with treatment) requires subjects to answer 4 questions related to how much their ADHD symptoms have changed since starting the medication, how much benefit they received from the medication, the extent, if any, the advantages outweighed the disadvantages, and overall satisfaction with the medication. The responses for this question vary with range of satisfaction (e.g. extremely satisfied, very satisfied, satisfied, neutral, dissatisfied, very dissatisfied, or extremely dissatisfied). | Endpoint (42 days or early discontinuation) | 
| Responder Rate Using AISRS | AISRS responder rate is defined as the percentage of subjects with AISRS < 18 at endpoint. | Endpoint (42 days or early discontinuation) | 
| Clinical Global Impression - Severity of Illness Subscale (CGI-S) | The Clinical Global Impression - Severity of Illness (CGI-S) is a clinician-rated subscale (low=0, high=7, higher score indicates increasing illness). The clinician rates the severity of the ADHD symptoms in relation to the clinician's total experience with ADHD subjects using a 7-point scale (1=normal, not at all ill, 2= borderline ill, 3= mildly ill, 4=moderately ill, 5= markedly ill, 6= severely ill, 7= among the most extremely ill subjects) in response to the question Considering your total clinical experience with this particular population, how ill is the subject at this time?. | Baseline, endpoint (42 days or early discontinuation) | 
| Significant Other's (a Spouse, Significant Other or Other Adult in the Household, Described in This Study as the Designated Observer) Rating of Adult ADHD Rating Scale IV | The ADHD Rating Scale-IV (Significant Other) is an 18-item list of core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms. Each item is rated on a four point Likert type scale (0 = never or rarely, 1 = sometimes, 2 = often, and 3 = very often). The subject's designated observer will complete this scale, with baseline assessment based on the subject's usual functioning when not on medication. The total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms). | Baseline, endpoint (42 days or early discontinuation) | 
| Designated Observer's (DO) Global Executive Composite (GEC) Score of the Brief Rating Inventory of Executive Function for Adults (BRIEF-A) | The BRIEF-A, as completed by the DO, is a measure (low=61, high=225, lower scores indicate higher executive functioning) capturing views of an adult informant familiar with the subject's functioning. The BRIEF-A contains 75 scored items (1=never, 2=sometimes, 3=often) in nine non-overlapping clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). The Behavioral Regulation Index (BRI), Metacognition Index (MI), and Global Executive Composite (GEC) are then derived. | Baseline, endpoint (42 days or early discontinuation) | 
| Designated Observer's (DO) Rating of Dyadic Satisfaction Subscale | The Dyadic Adjustment Scale (DAS) completed by DOs who were spouses or significant others assesses the relationship satisfaction or adjustment of partners in committed couple relationships. The 32-question DAS includes 4 empirically validated subscales that measure: dyadic satisfaction, dyadic consensus, dyadic cohesion and affectional expression. Possible responses include 5-, 6-, and 7-point Likert-scale questions and two yes/no items. The 10-question DAS subset, the Dyadic Satisfaction Subscale, was used in this study (low=0, high=50, higher score means better relationship satisfaction). | Baseline, endpoint (42 days or early discontinuation) | 
| Designated Observer's (DO) Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication for ADHD Your Partner is Taking? | The satisfaction with treatment questionnaire (low=0, high=20, a lower score indicates lower satisfaction with treatment) requires the subject's DO to answer 4 questions related to how much the subject's ADHD symptoms have changed since starting the medication, how much benefit was received from the medication, the extent, if any, the advantages outweighed the disadvantages, and overall satisfaction with the medication. Responses vary from extremely satisfied, very satisfied, satisfied, neutral, mildly dissatisfied, dissatisfied, very dissatisfied, or extremely dissatisfied. | Endpoint (42 days or early discontinuation) | 
| Adult ADHD Self-Report Scale (ASRS) Over Time | The Adult ADHD Self-Report Scale (ASRS) assesses 18 core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms for adult subjects based on the subject's own rating for each of the symptoms using a four point scale (0=None, 1=Mild, 2=Moderate, and 3=Severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The ASRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms). | Baseline, endpoint (42 days or early discontinuation) | 
| Pittsburgh Sleep Quality Index (PSQI) Total Score | The PSQI discriminates between good and poor sleepers. The self-administered scale contains 15 multiple-choice items concerning frequency of sleep disturbances and subjective sleep quality and 4 write-in items that inquire about typical bedtime, wake-up time, sleep latency, and sleep duration over the past month. The PSQI generates 7 scores corresponding to the different sleep domains. Each component score ranges from 0 to 3. Total sleep index is calculated by adding up the 7 component scores (low=0, high=21, the lower the score, the better in sleep quality). | Baseline, endpoint (42 days or early discontinuation) | 
| Epworth Sleepiness Scale (ESS) | The Epworth Sleepiness Scale (ESS) is an 8-item self-rated questionnaire designed to assess the overall level of daytime sleepiness. Each item describes normal daily situations (i.e., watching TV, lying down in the afternoon, sitting inactive in a public place) and subjects rate the likelihood of dozing off or falling asleep in each situation. Responses use a 4-point rating scale (0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing). Item scores are summed to produce a total score (range of 0-24) with lower score suggesting more alertness. | Baseline, endpoint (42 days or early discontinuation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osmotic Release Oral System (OROS®) Extended Release Methylphenidate HCl, CONCERTA® (OROS MPH)