Effects of Methylphenidate on Cellular Abnormalities in Children With Attention Deficit Hyperactivity Disorder (ADHD)

• The Number of Chromosomal Aberrations Per 100 Cells Excluding Gaps at Baseline and at the End of Treatment i.e Day 84 (Week 12) [ Time Frame: baseline and at end of treatment (Week 12) ] [ Designated as safety issue: Yes ]
  The number of chromosomal aberrations per 100 cells excluding gaps at Baseline (n=33, n=32) and at Week 12 (n=33, n=32) was counted in blood samples cultured for 48 hours using a standard protocol. The types of abnormalities included translocations (reciprocal and non-reciprocal), insertions, dicentrics, fragments, inversions, chromatid exchanges (quadriradials and triradials), breaks, and other unusual observations, eg, aneuploidy, tetraploidy or endoreduplication.
• The Number of Micronuclei Per 1000 Binucleated Cells Endpoints at Baseline and at the End of Treatment i.e Day 84 (Week 12) [ Time Frame: baseline and at end of treatment (Week 12) ] [ Designated as safety issue: Yes ]
  The number of micronuclei per 1000 binucleated cells was measured at Baseline ( n=34 , n=29 ) and at the end of treatment, Week 12 (n =34, n= 29), in blood cultured for 48 hours using a standard protocol.

• Number of Sister Chromatoid Exchanges Per Cell [ Time Frame: baseline and at end of treatment (Week 12) ] [ Designated as safety issue: Yes ]
  Blood collected at baseline (n=20, n=14) and at the end of treatment, Week 12, (n= 20, n= 14) was cultured for 48 hours using a standard protocol. Giemsa staining and/or fluorescent in situ hybridization (FISH) chromosome painting was done on the cells in metaphase and the number of chromatoid exchanges per cell was recorded by blinded raters.
• Pharmacokinetic/Pharmacodynamic Relationship of Methylphenidate Blood Levels and Cytogenetic Changes [ Time Frame: End of treatment (Week 12) ] [ Designated as safety issue: No ]
  Since no cytogenetic effects were observed, blood samples were not analyzed for pharmacokinetics/pharmacodynamics.
• Change From Baseline to End of Treatment (Week 12) on the Conners' ADHD/DSM-IV Scale for Parents (CADS-P) [ Time Frame: Baseline to end of treatment (Week 12) ] [ Designated as safety issue: No ]
  Parents completed the Conners' ADHD/DSM-IV Scale for Parents (CADS-P) consisting of the ADHD Index (12 items) and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)( 18 items). Parents rated their child's behavior of the previous week from a list of common problems. When asked "How much of a problem has this been in the last week?" parents selected 0 = none, not at all, seldom, or very infrequently; 3 = very much true, or it occurs very often or frequently; or 1 or 2 for ratings in between. A score of 50 is considered normal and more than 70 markedly atypical.
• Change From Baseline to the End of Treatment (Week 12) on the Global Improvement Rating of the Clinical Global Impression Scale (CGI-I) [ Time Frame: From baseline to the end of treatment (Week 12) ] [ Designated as safety issue: No ]
  The Clinical Global Impression scale (CGI-I) is a clinician-rated instrument designed to assess the overall change of illness relative to baseline. The CGI-I consists of 7 ratings as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. CGI-I assessments are relative to the patient's status at the Baseline visit.
• Change From Baseline to the End of Treatment (Week 12) on the Severity of Illness Rating of the Clinical Global Impression Scale (CGI-S) [ Time Frame: From baseline to the end of treatment (Week 12) ] [ Designated as safety issue: No ]
  The Clinical Global Impression scale (CGI-S) is a clinician-rated instrument designed to assess the severity of illness. The CGI-S rating indicates illness severity at each time-point on a scale as follows: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = extremely ill. CGI-S assessments are relative to the patient's status at the Baseline visit.

• Frequency of persistent chromosomal changes (stable translocations)
• Pharmacokinetic/Pharmacodynamic relationship of methylphenidate blood levels and cytogenetic changes
• Efficacy evaluation measured through Connors ADHD/DSM-IV Scale for parents, global Improvement rating of the Clinical Global Impression scale, and severity of illness rating of the Clinical Global Impression scale.

This study will assess the frequency of chromosomal abnormalities measured in circulating lymphocytes in treatment-naive children with Attention Deficit Hyperactivity Disorder (ADHD) treated for 3 months with either extended release methylphenidate or behavioral therapy.

This study will determine whether the administration of extended-release methylphenidate in treatment-naïve children with Attention Deficit Hyperactivity Disorder (ADHD) affects the frequency of chromosomal abnormalities.

• Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy
  Other Name: Ritalin LA
• Behavioral: Behavior Therapy

• Active Comparator: 1
  Intervention: Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy
• 2
  Intervention: Behavioral: Behavior Therapy

Inclusion Criteria:

• Children of both genders, 6-12 years old
• Written informed consent by the parent and the patient (over 7)
• Diagnosis of ADHD
• Age-appropriate cognitive functioning
• All patients who had at least one post-baseline cytogenetic assessment in the core study can enter the observation phase.

Exclusion Criteria:

• History of malignant neoplasm
• History of seizures (except childhood febrile seizures)
• Hyperthyroidism
• Concurrent medical condition which may interfere with study

Other protocol-defined inclusion/exclusion criteria may apply