An Effectiveness and Safety Study Evaluating OROS Methylphenidate Hydrochloride (HCl), Ritalin (Methylphenidate HCl) and Placebo in Children With Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder Clinical Trial

Official title:

Screening, Efficacy, and Safety Study Evaluating OROS (Methylphenidate HCl), Ritalin and Placebo in Children With ADHD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00269776
• Other study ID #: CR005989
• Secondary ID: CONCERTAATT3019C
• Status: Completed
• Phase: Phase 3
• First received: December 22, 2005
• Last updated: July 8, 2011
• Start date: November 1998
• Est. completion date: January 1999

Study information

• Verified date: July 2011
• Source: Alza Corporation, DE, USA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to provide data on the effectiveness of the OROS Methylphenidate Hydrochloride (HCl) formulation compared to placebo and standard immediate-release Ritalin with respect to improving attention and behavior, and decreasing hyperactivity in children with Attention Deficit Hyperactivity Disorder (ADHD). Both OROS Methylphenidate HCl and Ritalin contain the central nervous system stimulant, methylphenidate HCl. The safety associated with the two methylphenidate formulations will also be compared with placebo.

Description:

Attention Deficit Hyperactivity Disorder (ADHD) represents the most common neurobehavioral disorder in children, affecting 3% to 5% of the school-age population. Behavioral pediatricians, child psychiatrists, and child neurologists indicate that referrals for ADHD may constitute up to 50% of their practices. This is a double-blind, double-dummy, randomized, placebo-controlled, active-controlled, 3-treatment, 3-period crossover trial to compare the safety and effectiveness (onset of effect, time to loss of effect and overall efficacy) of OROS Methylphenidate Hydrochloride (HCl), with standard immediate-release Ritalin and placebo. During this study, patients receive each of the three treatments (OROS Methylphenidate HCl 18, 36 or 54 milligrams per day, Ritalin 5, 10 or 15 milligrams three times per day, or placebo) for 7 days, and are assigned to one of three dosage levels depending upon their prestudy methylphenidate dose and regimen. The total study participation for each patient will be 21 days. Since ADHD is manifested in a variety of settings and can affect attention and behavior, this study assesses efficacy in home, community school, and laboratory school settings using numerous assessments designed to evaluate various aspects of the disorder. These assessments are completed by a variety of raters, including the parents/caregivers, community school teachers, and laboratory school teachers. The primary measure of effectiveness is the community school teacher's rating on the IOWA Conners Inattention/Overactivity subscale. Additional measures of effectiveness include the IOWA Conners (Inattention/Overactivity and Oppositional/Defiance subscale) ratings, SKAMP attention and deportment ratings, peer interaction and other behavioral ratings, global assessments, SNAP-IV ratings, activity levels during structured activities, accuracy and productivity of independent assigned academic seatwork, and a home situation questionnaire. Safety evaluations include the incidence of adverse events, physical examinations, clinical laboratory tests, vital signs, sleep quality, actigraphy (sleep latency, duration, and arousals), appetite, and the presence/severity of tics (hard-to-control, repeated twitching of any parts of the body or hard-to-control repeating of sounds or words). Patients will be given oral doses of: OROS (methylphenidate HCl) 1, 2, or 3 of the 18-milligram tablets once daily, or Ritalin 5, 10, or 15 mg (encapsulated/single capsule) three times a day, or placebo. There are three treatment groups, each group dosing for 7 days for a total of 21 days on study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: January 1999
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 12 Years

Eligibility

Inclusion Criteria:

• Patients having a diagnosis of one of the three subtypes of Attention Deficit Hyperactivity Disorder (ADHD) verified by both a parent/child interview and a teacher assessment using SNAP-IV questionnaires

• taking or have taken in the past 5 - 20 mg of immediate-release methylphenidate (Ritalin) at least twice a day, 20 - 60 mg of sustained-release methylphenidate (Ritalin-SR) per day, or a combination of immediate-release and sustained-release methylphenidate up to a daily dose not exceeding 60 mg

• having used methylphenidate for at least 3 months at some time in the past without any significant adverse experiences, considered to be positive responders to methylphenidate therapy, and agreeing to take to take only the supplied study drug as treatment for ADHD during the three-week treatment phase of the study

• able to comply with the study visit schedule and whose parent(s) and teacher are willing and able to complete the protocol-specified assessments

• agreeing not to ingest any caffeine containing beverages (e.g., coffee or soda) or foods (e.g., chocolate) on days 7, 14, and 21 of the study.

Exclusion Criteria:

• Patients having clinically significant gastrointestinal problems, including narrowing of the gastrointestinal tract

• having glaucoma, an ongoing seizure disorder, a psychotic disorder, or have a diagnosis of Tourette's syndrome

• whose primary treatment focus is oppositional-defiant disorder, conduct disorder, or tics, or whose primary treatment focus is psychiatric conditions such as depressive disorders, bipolar disorders, or other mood disorders

• having a mean of two blood pressure measurements (systolic or diastolic) equal to or greater than the 95th percentile for age, sex, and height at screening

• if female, have begun menstruation.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Hyperkinesis

Intervention

Drug:
• Placebo
Treatment C: Three OROS placebo tablets once daily + 1 placebo capsule 3x times/day for 7 days. Each patient will be randomized to 1 of 9 treatment sequences each consisting of 3 7-day treatment periods of Treatment A, B, and C.
• OROS (methylphenidate HCl)
Treatment A: 1, 2, or 3 OROS methylphenidate 18-mg tablets + 0, 1, or 2 OROS placebo tablets (3 tablets in total) once daily + 1 placebo capsule 3x/day for 7 days. Each patient will be randomized to 1 of 9 treatment sequences each consisting of 3 7-day treatment periods of Treatment A, B, and C.
• Ritalin (methylphenidate)
Treatment B: 5, 10, or 15-mg tablets (encapsulated/single capsule) 3 times a day + 3 OROS placebo tablets once daily for 7 days. Each patient will be randomized to 1 of 9 treatment sequences each consisting of 3 7-day treatment periods of Treatment A, B, and C.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Alza Corporation, DE, USA

References & Publications (1)

Swanson J, Gupta S, Lam A, Shoulson I, Lerner M, Modi N, Lindemulder E, Wigal S. Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies. A — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IOWA Conners Inattention/Overactivity subscale ratings by the Community School Teacher		Up to Day 6 of each treatment period for a total of approximatly 18 days	No
Secondary	SKAMP attention and deportment ratings		Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days	No
Secondary	Peer interaction ratings		Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days	No
Secondary	Laboratory School Teacher Global Assessments		Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days	No
Secondary	SNAP-IV ratings		Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days	No
Secondary	Incidence of adverse events		Up to Day 7 of each of 3 treatment periods for a total of approximately 21 days	No