<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02215538</url>
  </required_header>
  <id_info>
    <org_study_id>00012246</org_study_id>
    <nct_id>NCT02215538</nct_id>
  </id_info>
  <brief_title>OROS Methylphenidate (Concerta) in the Treatment of Adult ADHD</brief_title>
  <official_title>Concerta in the Treatment of Adult ADHD and a Comparison of Four Adult ADHD Scales and Effects on Personality</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>McNeil Consumer &amp; Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will look at the effectiveness of osmotic release oral system (OROS)&#xD;
      methylphenidate (Concerta) in treating attention deficit hyperactvity disorder (ADHD) in&#xD;
      adults. Concerta has received FDA approval for childhood ADHD and there is documentation that&#xD;
      it is effective in adult ADHD. However this trial will explore its effectiveness in treating&#xD;
      symptoms not a part of the Diagnostic and Statistical Manual-III (DSM-III) criteria. Subjects&#xD;
      will experience one screening visit and one baseline visit. Those who meet admission criteria&#xD;
      will enter the double-blind phase. This will involve two 4-week treatment periods one of&#xD;
      which will involve the use of Concerta and the other a placebo pill. Subjects who complete&#xD;
      the double-blind phase will be allowed to enter a 180-day, open-label Concerta phase designed&#xD;
      to assess long-term effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ADHD affects from 3 to 5% of children, persists into adolescence 40 to 70% of these children&#xD;
      and continues into adulthood in at least 50% of affected adolescents. Pharmacotherapy for&#xD;
      ADHD in adults has paralleled that used for children, with generally positive results&#xD;
      (Spencer, 1998). Never-the-less, it is not clear that the dimensions of medication response&#xD;
      in adults are the same as in children. The extent to which the symptoms change with age&#xD;
      remains open to question. This trial is created to include a variety of outcome measures&#xD;
      which will enhance the number of symptoms assessed.&#xD;
&#xD;
      Methylphenidate was the first medication shown to be effective in treatment for adults with&#xD;
      ADHD and continues to be widely used. Several studies have demonstrated the usefulness of&#xD;
      methylphenidate in adult ADHD (Wender et al, 1985, Spencer et al, 1995). These studies have&#xD;
      not shown any unexpected drawbacks to treatment with methylphenidate. The extended release&#xD;
      formulations represent an improvement over the immediate release versions for many patients.&#xD;
&#xD;
      This is a double-blind, placebo-controlled, randomized, crossover trial comparing OROS&#xD;
      methylphenidate with placebo. The double-blind trial will be preceded by an enrollment period&#xD;
      consisting of a screening visit followed by a baseline visit. Patients who continue to meet&#xD;
      admission criteria at baseline will be randomized into the first of two 4-week treatment&#xD;
      periods. We will attempt to reach the highest tolerated dose size within 2 weeks and then&#xD;
      observe the response over the last two weeks of each crossover phase. The double-blind period&#xD;
      will be followed by a 180 day open-treatment, flexible-dose phase designed to assess&#xD;
      long-term effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2004</start_date>
  <completion_date type="Actual">June 2006</completion_date>
  <primary_completion_date type="Actual">February 2006</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS)</measure>
    <time_frame>Baseline visit, Double-blind phase Week 4 each arm, Open-Label months 1-6</time_frame>
    <description>This is an investigator rated scale which assessed the 7 domains of the Utah Criteria of Adult ADHD</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impressions-Improvement (CGI-I)</measure>
    <time_frame>Baseline; Double-blind phase Week 4 each arm: Open-Label months 1-6</time_frame>
    <description>This is a global measure in improvement in symptoms that is a Likert type scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Severity (CGI-S)</measure>
    <time_frame>Baseline visit; Double-blind phase Week 4 each arm: Open-Label months 1-6</time_frame>
    <description>This is a general measure of symptom severity assessed using a Likert type scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ADHD rating scale (ADHD-RS)</measure>
    <time_frame>Baselinevisit; Double-blind phase Week 4 each arm: Open-Label final visit month 6</time_frame>
    <description>This is an investigator rated scale which assesses the DSM-IV symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self Report Wender-Reimherr Adult Attention Deficit Disorder Scale (SR-WRAADDS)</measure>
    <time_frame>Baseline; Double-blind phases Week 4 each arm: Final visit of Open-Label period month 6</time_frame>
    <description>This is a patient rated scale that assesses the 7 domains of the Utah Criteria for adult ADHD as well as ODD, Social functioning and Learning difficulties.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wisconsin Personality Inventory - IV (WISPI-IV)</measure>
    <time_frame>Baseline visit; Final Open-Label visit month 6</time_frame>
    <description>This is a computerized personality inventory completed by the patients. It consists of 214 items which address the 10 DSM-IV personality disorders plus passive aggressive personality disorder.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Attention Deficit Hyperactivity Disorder</condition>
  <arm_group>
    <arm_group_label>OROS methylphenidate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This was a 4-week double-blind arm. Medication was initiated at 18 mg/day and increased every 2 or 3 days by 9 mg based on treatment response and side effects. Maximum dose - 90 mg/day. Patients were seen weekly. Generally a stable dose was seen in 2 weeks and maintained the last 2 weeks of the arm. Side effects were assessed at each visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>This arm was identical to the active medication arm except that placebo replaced the active medication.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OROS methylphenidate</intervention_name>
    <arm_group_label>OROS methylphenidate</arm_group_label>
    <other_name>concerta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo medication appears identical to the active medication OROS methylphenidate</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Adults meeting DSM-IV-Text Revision criteria for ADHD, the Utah Criteria for ADHD, and&#xD;
        experiencing at least moderate impairment (a score of 4 or greater on the CGI-Severity&#xD;
        Scale for ADHD at both Screening and Baseline visits) will be enrolled. Other criteria&#xD;
        include:&#xD;
&#xD;
          1. Subjects ages 18 to 65, inclusive;&#xD;
&#xD;
          2. Female subjects are eligible to enter and participate in this study only if:&#xD;
&#xD;
               -  She is of non-childbearing potential; has a male sexual partner who is surgically&#xD;
                  sterilized; is on implant of levonorgestrel, injectable progesterone, or an oral&#xD;
                  contraceptive; has an intrauterine device (IUD); or is sexually inactive with a&#xD;
                  male partner.&#xD;
&#xD;
               -  Or agrees to use a double barrier method of contraception (any combination of&#xD;
                  physical and chemical methods) and has a negative urine pregnancy test at&#xD;
                  screening interview.&#xD;
&#xD;
          3. Subject must be in general good health as determined by medical history, ECG, and&#xD;
             other analysis that, in the judgment of the study physician, would confirm the&#xD;
             patient's good health.&#xD;
&#xD;
          4. Subjects must read and write at a level sufficient to provide written informed consent&#xD;
             and complete study-related materials.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with other current DSM-IV Axis I Disorders including Current or lifetime&#xD;
             history of psychosis, current bipolar disorder type I, current Major Depressive&#xD;
             Disorder, and Current Anxiety Disorder (unless in the opinion of clinic physician ADHD&#xD;
             is the primary disorder and causes the disability seen in the patient);&#xD;
&#xD;
          2. Subjects with any other DSM-IV Axis II diagnosis so severe that it would suggest&#xD;
             non-responsiveness to pharmacotherapy for ADHD or noncompliance with the protocol;&#xD;
&#xD;
          3. Subjects at risk for suicide or a risk to harm others;&#xD;
&#xD;
          4. History of Substance Dependence according to DSM-IV criteria within 3 months of&#xD;
             screening;&#xD;
&#xD;
          5. Subjects currently abusing illegal drugs or alcohol are excluded from the study;&#xD;
&#xD;
          6. Positive urine screen for drugs of abuse at screening for patients who have a&#xD;
             significant history of substance use but still meet criteria 4 and 5. Patients not at&#xD;
             risk for substance abuse will not be given a urine drug screen;&#xD;
&#xD;
          7. Subjects in whom stimulants would represent a risk such as those with a history of&#xD;
             stimulant abuse,&#xD;
&#xD;
          8. History of uncontrolled hypertension or significant cardiovascular disease;&#xD;
&#xD;
          9. Any known or suspected significant medical or psychiatric illnesses (e.g., hepatic or&#xD;
             renal insufficiency, pulmonary (asthma, chronic obstructive pulmonary disease, etc),&#xD;
             gastrointestinal, endocrine, neurological or metabolic disturbances that, in the&#xD;
             judgment of the investigator, may impair interpretation of study results or constitute&#xD;
             a significant safety concern in the context of the clinical trial;&#xD;
&#xD;
         10. Medications, including health food supplements judged by the investigator to be likely&#xD;
             to have central nervous system activity (for example, St John's Wort, gingko leaf, and&#xD;
             melatonin), are not permitted during the study. If the subject is taking the&#xD;
             medication prior to study entry, there must be a 7 day washout period prior to Visit&#xD;
             2. We will ask for an honest report of all medications consumed between visits. In the&#xD;
             event a medication with psychoactive properties is consumed, the patient will be&#xD;
             counseled regarding the use of prohibited medications;&#xD;
&#xD;
         11. Use of any medication not considered acceptable by the clinical investigator or the&#xD;
             medical monitor during the 7-day period before the start of the study (Day 1);&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frederick W Reimherr, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univeristy of Utah Dept of Psychiatry</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mood Disorders Clinic</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Marchant BK, Reimherr FW, Halls C, Williams ED, Strong RE. OROS methylphenidate in the treatment of adults with ADHD: a 6-month, open-label, follow-up study. Ann Clin Psychiatry. 2010 Aug;22(3):196-204.</citation>
    <PMID>20680193</PMID>
  </results_reference>
  <results_reference>
    <citation>Reimherr FW, Marchant BK, Williams ED, Strong RE, Halls C, Soni P. Personality disorders in ADHD Part 3: Personality disorder, social adjustment, and their relation to dimensions of adult ADHD. Ann Clin Psychiatry. 2010 May;22(2):103-12.</citation>
    <PMID>20445837</PMID>
  </results_reference>
  <results_reference>
    <citation>Robison RJ, Reimherr FW, Gale PD, Marchant BK, Williams ED, Soni P, Halls C, Strong RE. Personality disorders in ADHD Part 2: The effect of symptoms of personality disorder on response to treatment with OROS methylphenidate in adults with ADHD. Ann Clin Psychiatry. 2010 May;22(2):94-102.</citation>
    <PMID>20445836</PMID>
  </results_reference>
  <results_reference>
    <citation>Williams ED, Reimherr FW, Marchant BK, Strong RE, Halls C, Soni P, Gale PD, Robison RJ. Personality disorder in ADHD Part 1: Assessment of personality disorder in adult ADHD using data from a clinical trial of OROS methylphenidate. Ann Clin Psychiatry. 2010 May;22(2):84-93.</citation>
    <PMID>20445835</PMID>
  </results_reference>
  <results_reference>
    <citation>Reimherr FW, Williams ED, Strong RE, Mestas R, Soni P, Marchant BK. A double-blind, placebo-controlled, crossover study of osmotic release oral system methylphenidate in adults with ADHD with assessment of oppositional and emotional dimensions of the disorder. J Clin Psychiatry. 2007 Jan;68(1):93-101. doi: 10.4088/jcp.v68n0113.</citation>
    <PMID>17284136</PMID>
  </results_reference>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 8, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>August 12, 2014</last_update_submitted>
  <last_update_submitted_qc>August 12, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 13, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>frederick reimherr</investigator_full_name>
    <investigator_title>Director, Mood Disorders Clinic</investigator_title>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>adult</keyword>
  <keyword>WRAADDS</keyword>
  <keyword>OROS MPH</keyword>
  <keyword>emotional dysregulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Attention Deficit Disorder with Hyperactivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02215538
org study id: 00012246
nct id: NCT02215538
lead sponsor: 
collaborator: 
has dmc: Yes
This study will look at the effectiveness of osmotic release oral system (OROS)
      methylphenidate (Concerta) in treating attention deficit hyperactvity disorder (ADHD) in
      adults. Concerta has received FDA approval for childhood ADHD and there is documentation that
      it is effective in adult ADHD. However this trial will explore its effectiveness in treating
      symptoms not a part of the Diagnostic and Statistical Manual-III (DSM-III) criteria. Subjects
      will experience one screening visit and one baseline visit. Those who meet admission criteria
      will enter the double-blind phase. This will involve two 4-week treatment periods one of
      which will involve the use of Concerta and the other a placebo pill. Subjects who complete
      the double-blind phase will be allowed to enter a 180-day, open-label Concerta phase designed
      to assess long-term effects.
ADHD affects from 3 to 5% of children, persists into adolescence 40 to 70% of these children
      and continues into adulthood in at least 50% of affected adolescents. Pharmacotherapy for
      ADHD in adults has paralleled that used for children, with generally positive results
      (Spencer, 1998). Never-the-less, it is not clear that the dimensions of medication response
      in adults are the same as in children. The extent to which the symptoms change with age
      remains open to question. This trial is created to include a variety of outcome measures
      which will enhance the number of symptoms assessed.

      Methylphenidate was the first medication shown to be effective in treatment for adults with
      ADHD and continues to be widely used. Several studies have demonstrated the usefulness of
      methylphenidate in adult ADHD (Wender et al, 1985, Spencer et al, 1995). These studies have
      not shown any unexpected drawbacks to treatment with methylphenidate. The extended release
      formulations represent an improvement over the immediate release versions for many patients.

      This is a double-blind, placebo-controlled, randomized, crossover trial comparing OROS
      methylphenidate with placebo. The double-blind trial will be preceded by an enrollment period
      consisting of a screening visit followed by a baseline visit. Patients who continue to meet
      admission criteria at baseline will be randomized into the first of two 4-week treatment
      periods. We will attempt to reach the highest tolerated dose size within 2 weeks and then
      observe the response over the last two weeks of each crossover phase. The double-blind period
      will be followed by a 180 day open-treatment, flexible-dose phase designed to assess
      long-term effects.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS)
time frame: Baseline visit, Double-blind phase Week 4 each arm, Open-Label months 1-6
description: This is an investigator rated scale which assessed the 7 domains of the Utah Criteria of Adult ADHD
measure: Clinical Global Impressions-Improvement (CGI-I)
time frame: Baseline; Double-blind phase Week 4 each arm: Open-Label months 1-6
description: This is a global measure in improvement in symptoms that is a Likert type scale
measure: Clinical Global Impression - Severity (CGI-S)
time frame: Baseline visit; Double-blind phase Week 4 each arm: Open-Label months 1-6
description: This is a general measure of symptom severity assessed using a Likert type scale.
measure: ADHD rating scale (ADHD-RS)
time frame: Baselinevisit; Double-blind phase Week 4 each arm: Open-Label final visit month 6
description: This is an investigator rated scale which assesses the DSM-IV symptoms.
measure: Self Report Wender-Reimherr Adult Attention Deficit Disorder Scale (SR-WRAADDS)
time frame: Baseline; Double-blind phases Week 4 each arm: Final visit of Open-Label period month 6
description: This is a patient rated scale that assesses the 7 domains of the Utah Criteria for adult ADHD as well as ODD, Social functioning and Learning difficulties.
measure: Wisconsin Personality Inventory - IV (WISPI-IV)
time frame: Baseline visit; Final Open-Label visit month 6
description: This is a computerized personality inventory completed by the patients. It consists of 214 items which address the 10 DSM-IV personality disorders plus passive aggressive personality disorder.
arm group label: OROS methylphenidate
arm group type: Experimental
description: This was a 4-week double-blind arm. Medication was initiated at 18 mg/day and increased every 2 or 3 days by 9 mg based on treatment response and side effects. Maximum dose - 90 mg/day. Patients were seen weekly. Generally a stable dose was seen in 2 weeks and maintained the last 2 weeks of the arm. Side effects were assessed at each visit.
arm group label: placebo
arm group type: Placebo Comparator
description: This arm was identical to the active medication arm except that placebo replaced the active medication.
intervention type: Drug
intervention name: OROS methylphenidate
arm group label: OROS methylphenidate
other name: concerta
intervention type: Drug
intervention name: Placebo
description: Placebo medication appears identical to the active medication OROS methylphenidate
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Frederick W Reimherr, MD
role: Principal Investigator
affiliation: Univeristy of Utah Dept of Psychiatry
facility: 
country: United States
citation: Marchant BK, Reimherr FW, Halls C, Williams ED, Strong RE. OROS methylphenidate in the treatment of adults with ADHD: a 6-month, open-label, follow-up study. Ann Clin Psychiatry. 2010 Aug;22(3):196-204.
PMID: 20680193
citation: Reimherr FW, Marchant BK, Williams ED, Strong RE, Halls C, Soni P. Personality disorders in ADHD Part 3: Personality disorder, social adjustment, and their relation to dimensions of adult ADHD. Ann Clin Psychiatry. 2010 May;22(2):103-12.
PMID: 20445837
citation: Robison RJ, Reimherr FW, Gale PD, Marchant BK, Williams ED, Soni P, Halls C, Strong RE. Personality disorders in ADHD Part 2: The effect of symptoms of personality disorder on response to treatment with OROS methylphenidate in adults with ADHD. Ann Clin Psychiatry. 2010 May;22(2):94-102.
PMID: 20445836
citation: Williams ED, Reimherr FW, Marchant BK, Strong RE, Halls C, Soni P, Gale PD, Robison RJ. Personality disorder in ADHD Part 1: Assessment of personality disorder in adult ADHD using data from a clinical trial of OROS methylphenidate. Ann Clin Psychiatry. 2010 May;22(2):84-93.
PMID: 20445835
citation: Reimherr FW, Williams ED, Strong RE, Mestas R, Soni P, Marchant BK. A double-blind, placebo-controlled, crossover study of osmotic release oral system methylphenidate in adults with ADHD with assessment of oppositional and emotional dimensions of the disorder. J Clin Psychiatry. 2007 Jan;68(1):93-101. doi: 10.4088/jcp.v68n0113.
PMID: 17284136
responsible party type: Principal Investigator
investigator affiliation: University of Utah
investigator full name: frederick reimherr
investigator title: Director, Mood Disorders Clinic
mesh term: Attention Deficit Disorder with Hyperactivity
mesh term: Methylphenidate