Open-label Extension Evaluating Methylphenidate Hydrochloride Extended Release in Adults With Attention Deficit/Hyperactivity Disorder

A 6-month, Open-label Extension to a 40-week, Randomized, Double-blind, Placebo-controlled, Multicenter Efficacy and Safety Study of Methylphenidate Hydrochloride Extended Release in the Treatment of Adult Patients With Childhood-onset ADHD

This study will evaluate the long-term safety of methylphenidate hydrochloride extended release in adults with attention deficit/hyperactivity disorder

Study Overview

• Status: Completed
• Conditions: Attention Deficit/Hyperactivity Disorder
• Intervention / Treatment: Drug: Ritalin LA (methylphenidate hydrochloride extended release)

• Study Type: Interventional
• Enrollment (Actual): 299
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, 8310
    • Novartis Investigative Site
  • Heusden-Zolder, Belgium, 3550
    • Novartis Investigative Site
  • Kessel-Lo, Belgium, 3010
    • Novartis Investigative Site
  • Mechelen, Belgium, 2800
    • Novartis Investigative Site
  • Uccle, Belgium, 1180
    • Novartis Investigative Site
• Colombia
  • Antioquia, Colombia, 0000
    • Novartis Investigative Site
  • Antioquia, Colombia
    • Novartis Investigative Site
• Denmark
  • Århus C, Denmark, 8000
    • Novartis Investigative Site
• Germany
  • Bamberg, Germany, 96047
    • Novartis Investigative Site
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Berlin, Germany, 10629
    • Novartis Investigative Site
  • Dresden, Germany, 01129
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Freiburg, Germany, 79104
    • Novartis Investigative Site
  • Hamburg, Germany, 20259
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Landau, Germany, 76829
    • Novartis Investigative Site
  • Leipzig, Germany, 04157
    • Novartis Investigative Site
  • Limburg, Germany, 65549
    • Novartis Investigative Site
  • Ludwigsburg, Germany, 71636
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Mannheim, Germany, 68159
    • Novartis Investigative Site
  • München, Germany, 80333
    • Novartis Investigative Site
  • Naumburg, Germany, 06618
    • Novartis Investigative Site
  • Nürnberg, Germany, 90419
    • Novartis Investigative Site
  • Siegen, Germany, 57076
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Westerstede/Oldenburg, Germany, 26655
    • Novartis Investigative Site
  • Wolfsburg, Germany, 38444
    • Novartis Investigative Site
  • Würzburg, Germany, 97070
    • Novartis Investigative Site
• Sweden
  • Luleå, Sweden, 972 35
    • Novartis Investigative Site
  • Malmö, Sweden, 211 53
    • Novartis Investigative Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Novartis Investigative Site
  • California
    • Beverly Hills, California, United States, 90210
      • Novartis Investigative Site
    • Spring Valley, California, United States, 91978-1522
      • Novartis Investigative Site
  • Florida
    • Bradenton, Florida, United States, 34208
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32806
      • Novartis Investigative Site
    • West Plam Beach, Florida, United States, 33407
      • Novartis Investigative Site
  • Illinois
    • Libertyville, Illinois, United States, 60048
      • Novartis Investigative Site
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Novartis Investigative Site
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Novartis Investigative Site
    • Las Vegas, Nevada, United States, 89128
      • Novartis Investigative Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Novartis Investigative Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19149
      • Novartis Investigative Site
  • Texas
    • Houston, Texas, United States, 77007
      • Novartis Investigative Site
  • Washington
    • Bellevue, Washington, United States, 98004
      • Novartis Investigative Site
    • Seattle, Washington, United States, 98104
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Completion of the 40-week core study CRIT124D2302 and Week 40 (End of Study) assessments or Patients who meet predefined criteria for treatment failure, were withdrawn from the core study, and have completed core-study week 40 assessments (Premature Discontinuation Visit)

Exclusion Criteria:

1. Patients who, during the core study, developed any psychiatric condition that requires treatment with medication or that may interfere with study participation and /or study assessments.
2. Patients who during the core study developed cardiovascular disorders.
3. Pregnant women.
4. Patients who developed seizures during the core study.
5. Diagnosis of glaucoma, hyperthyroidism, pheochromocytoma.
6. Diagnosis or family history of Tourette's syndrome.
7. Patients who during the core study developed cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis and stroke

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ritalin LA; All participants started with Ritalin LA 20 mg/day and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 40, 60 or 80 mg/day).

Drug: Ritalin LA (methylphenidate hydrochloride extended release); Ritalin LA 20 mg or 30 mg (a racemic mixture of d- and l-thre-Methylphenidate Hydrocloride (MPH), Extended release hard capsules) taken orally once daily in doses of 40, 60, or 80 mg. For 40mg dose patients took (2) Ritalin LA 20mg daily, for 60mg patients took (2) Ritalin LA 30mg daily and for 80mg patients took (2) Ritalin LA 30mg daily + (1) Ritalin LA 20mg daily for their optimal dose.; Other Names: Ritalin LA, methylphenidate hydrochloride extended release, RIT124D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events, Serious Adverse Events and Deaths.	Adverse Events, Serious Adverse Events and Deaths were monitored from week 40 to week 66.	Week 40 - Week 66

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Extension Baseline (Week 40) to End of Study (Week 66) in on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score.	Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) total score consists of 18 items directly adapted from the ADHD symptom list according to the DSM-IV. The DSM-IV ADHD RS total score was calculated as the sum of the Inattentive and the Hyperactive-Impulsive subscores. The 18 items are rated from 0 ("rarely or never") to 3 ("Very often"). The total score ranges from 0 to 54. Decrease in the DSM-IV ADHD RS total score indicates improvement, therefore a greater decrease (change at Final Visit compared to baseline) indicates a greater improvement in ADHD symptoms. Last Observation Carried Forward (LOCF) applied for each patient with data in extension period. If no post-baseline is available, it is considered as missing.	week 40 - week 66
Change From Extension Baseline (Week 40) to End of Study (Week 66) on Sheehan Disability Scale (SDS) Total Score	SDS,5-self-rated questionnaire to measure the extent a pt's disability due to an illness/health problem interferes with work/school,social life/leisure,family life/home. First 3 items, pts are asked how their symptoms disrupted their regular activities over the past 7d in each using a scale from 0(not at all)-10(extremely) Each subscale(work disability, social life disability, family life disability)can be scored independently or combined into a total score(sum of the non-missing responses for items 1-3)from 0-30,higher scores indicate significant functional impairment. Subscale scores>5 suggest impairment in that subscale area. Final 2 items ask pts about the # of days their symptoms caused them to miss school/work and # of days their symptoms caused them to be underproductive at school/work.(These items were not included in the total score.) Before responding to SDS items 1-3, pts were verbally instructed to recall the past 7d, items 4-5 refer to the last week w/in the item wording.	week 40 - week 66

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Boesen K, Paludan-Muller AS, Gotzsche PC, Jorgensen KJ. Extended-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2022 Feb 24;2(2):CD012857. doi: 10.1002/14651858.CD012857.pub2.
• Ginsberg Y, Arngrim T, Philipsen A, Gandhi P, Chen CW, Kumar V, Huss M. Long-term (1 year) safety and efficacy of methylphenidate modified-release long-acting formulation (MPH-LA) in adults with attention-deficit hyperactivity disorder: a 26-week, flexible-dose, open-label extension to a 40-week, double-blind, randomised, placebo-controlled core study. CNS Drugs. 2014 Oct;28(10):951-62. doi: 10.1007/s40263-014-0180-4.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: April 18, 2011
• First Posted (Estimate): April 20, 2011

Study Record Updates

• Last Update Posted (Estimate): November 24, 2014
• Last Update Submitted That Met QC Criteria: November 4, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: hyperactivity; Attention Deficit /Hyperactivity Disorder,
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: CRIT124D2302E1; 2011-000210-19