A Study to Evaluate Effectiveness and Safety of Prolonged Release OROS Methylphenidate in Adults With Attention Deficit Hyperactivity Disorder

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of 2 fixed dosages of Prolonged Release (PR) OROS methylphenidate (54 and 72 mg/day) compared with placebo in adult patients with attention deficit/hyperactivity disorder (ADHD).

Detailed Description
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The primary objective of this study is to evaluate the efficacy of 2 fixed dosages of Prolonged Release (PR) OROS methylphenidate (54 and 72 mg/day) compared with placebo in adult patients with attention deficit/hyperactivity disorder (ADHD). The primary efficacy criterion will be the change in the sum of the inattention and hyperactivity/impulsivity subscale scores of the investigator-rated Conners' Adult ADHD Rating Scale (CAARS), from start of treatment to the end of the double-blind treatment. Hypothesis of the primary objective states that either PR OROS methylphenidate dose is more effective than placebo after 13 weeks of treatment in adult patients with ADHD. This is a multicentre, double-blind, randomized, placebo-controlled, parallel group, dose-response study. Patients will be randomized into one of 3 treatment groups to receive oral dosages of PR OROS methylphenidate 54 or 72 mg, or placebo once daily. The study includes a treatment period of 13 weeks. Patients will be titrated from a starting dose of 36 mg/day for 7 days, to 54 or 72 mg/day at Day 8, after which treatment will be administered for 12 weeks. The study will include a screening period of up to 2 weeks, during which current therapy, not allowed during the study can be tapered down and discontinued (with the exception of fluoxetine or MAO (monoamine oxidase) inhibitors for which a maximum screening period of 4 weeks will be allowed). A post-study visit for collection of additional efficacy and safety data will be scheduled for one week after a patient's final dose of study drug. Adults with a diagnosis of ADHD according to DSM-IV criteria with some symptoms before age 7 years that continue to meet these criteria at the time of assessment will be enrolled in this study. ADHD is not diagnosed if the symptoms are better accounted for by another psychiatric disorder (e.g. mood disorder, anxiety disorder, psychotic disorder, personality disorder). The patient (and if possible, informant) must also describe a chronic course of ADHD symptomatology from childhood to adulthood. The description of this chronic course can be patient-based and previous documented diagnosis and/or treatment is not required. Approximately 300 patients (100 in each randomized treatment group) will participate in this study. The primary efficacy criterion will be the change in the sum of the inattention and hyperactivity/impulsivity subscale scores of the investigator-rated CAARS from baseline to the end of treatment (end of 13 weeks or last post-baseline assessment). This variable will be compared between each dosage group and placebo using an ANCOVA model. Other end points will include changes from baseline to the end of the treatment in the CAARS subscales and assessment of the clinical global impression - global change subscale (CGI-C). Onset of therapeutic effect and responder rate will also be determined. In addition, morning / evening (8 pm) CAARS-S:S assessments will be performed at baseline and on Days 34, 35, 90 and 91. Safety evaluations will include monitoring of adverse events (AEs), clinical laboratory tests (hematology; biochemistry), pregnancy testing, vital signs (supine and standing blood pressure, pulse) and weight, ECG. Patients will be randomized to receive PR OROS methylphenidate 54 or 72 mg, or placebo once daily. Study drug will be administered daily in the morning for up to 13 weeks. Since there is no food effect with methylphenidate, drug administration can be under fed or fasted conditions. Patients will start at a dosage of 36 mg. At Week 2, patients will receive 54 or 72 mg PR OROS methylphenidate for 12 weeks.

Official Title
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A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Response Study to Evaluate Efficacy and Safety of Prolonged Release (PR) OROS Methylphenidate (54 and 72 mg/Day) in Adults With Attention Deficit/Hyperactivity Disorder

Conditions
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Attention Deficit/ Hyperactivity Disorder

Intervention / Treatment
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* Drug: prolonged release (PR) OROS methylphenidate 54 mg
* Drug: prolonged release (PR) OROS methylphenidate 72 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ADHD according to the Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition (DSM-IV) and confirmed by the Conners' Adult ADHD Diagnostic Interview for DSM IV Described chronic course of ADHD symptomatology from childhood to adulthood, with some symptoms present before age 7 years and continue to meet DSM-IV criteria at the time of assessment CAARS score of at least or equal to 24 as determined by investigator at screening visit Patient agrees to take only the supplied study drug as treatment for ADHD during the study Patient agrees not to initiate a new behavioral modification program during the study or if currently using a behavioral modification program agrees not to change this program during the study. Exclusion Criteria: Known to be a non-responder to methylphenidate, or patient has a child known to be a non-responder to methylphenidate Has been treated with any methylphenidate-containing medication within 1 month of screening visit Participation in and premature withdrawal from 42603ATT3002, CR002479 or 42603ATT3004, CR011068 study Known allergy or hypersensitivity to methylphenidate, or components of PR OROS methylphenidate Any clinically unstable psychiatric condition including, but not limited to the following: acute mood disorder, bipolar disorder, acute obsessive-compulsive disorder (OCD), anti-social personality disorder, borderline personality disorder.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>prolonged release (PR) OROS methylphenidate 54 mg 18+36mg once daily for 13 weeks | Drug: prolonged release (PR) OROS methylphenidate 54 mg<br>* 18+36mg once daily for 13 weeks<br>|
| Experimental: 002<br>prolonged release (PR) OROS methylphenidate 72 mg 2x36mg once daily for 13 weeks | Drug: prolonged release (PR) OROS methylphenidate 72 mg<br>* 2x36mg once daily for 13 weeks<br>|
| Placebo Comparator: 003<br>Placebo 2xplacebo once daily for 13 weeks | Drug: Placebo<br>* 2xplacebo once daily for 13 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attention Deficit/Hyperactivity Disorder (ADHD) Symptoms Total Score of the Conners Adult ADHD Rating Scale (CAARS) | The primary endpoint was the change in the ADHD symptoms total score of the investigator-rated CAARS from baseline to the last assessment in the double-blind treatment period. CAARS assesses ADHD symptoms and behaviors in adults using a scale ranging from 0 (best) to 54 (worst). For subjects without a post-baseline efficacy measurement, a change of 0 units was imputed. | from baseline to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinical Global Impression-Severity (CGI-S) From Baseline to End of Treatment | The CGI-S rating scale is used to rate the severity of a subject's illness on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe illness). The change in CGI-S was assessed from baseline to end of treatment (week 13 or or last post-baseline assessment) | from baseline to13 weeks | 
| Clinical Global Impression-Change (CGI-C) | The CGI-C rating scale is used to rate the change in severity of the subject's illness compared to baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). | 13 weeks | 
| Change in Conners Adult ADHD Rating Scale Self Report Short Version (CAARS-S:S) Total Score | The CAARS-S:S is a 26-item self-report scale that measures symptoms based on the DSM-IV criteria for ADHD. Respondents were asked to rate items pertaining to their behavior/problems using the following 4-point scale (from 0 = Not at all, never; to 3 = Very much, very frequently). The CAARS-S:S total score range is from 0 (best) to 78 (worse). The change in CAARS-S:S was assessed from baseline to end of treatment (week 13 or or last post-baseline assessment) | from baseline to 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult, ADHD, Concerta