Efficacy and Safety Study of Methylphenidate Hydrochloride Extended Release in Adults With Childhood-onset Attention Deficit/Hyperactivity Disorder (ADHD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01259492
First received: December 11, 2010
Last updated: September 29, 2014
Last verified: September 2014
  Purpose

This study will evaluate efficacy and safety of methylphenidate hydrochloride extended release compared to placebo in adult patients with childhood-onset attention deficit/hyperactivity disorder (ADHD).


Condition Intervention Phase
Attention Deficit/Hyperactivity Disorder
Drug: Placebo
Drug: Ritalin LA 20 mg
Drug: Ritalin LA 30 mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 40-week, Randomized, Double-blind, Placebo-controlled, Multicenter Efficacy and Safety Study of Methylphenidate HCl Extended Release in the Treatment of Adult Patients With Childhood-onset ADHD

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment [ Time Frame: Baseline 1 to End of Period 1 (Week 9) ] [ Designated as safety issue: No ]
    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 ("Never") to 4 ("Very often"). The total score ranges from 0(least symptomatic) to 72 (most symptomatic). 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. 30% improvement: 100×(DSM-IV ADHD RS total score during Period 1 - DSM-IV ADHD RS total score at randomization(visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) <= - 30%.

  • Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment [ Time Frame: Baseline 1 to End of Period 1 (Week 9) ] [ Designated as safety issue: No ]
    SDS, a 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 reg. activities over the past 7d in ea. using a scale from 0(not at all)-10(extremely) Ea. 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 impairmt. 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.

  • Percentage of Participants With Treatment Failures During Period 3 [ Time Frame: Baseline Period 1 (Baseline 1) and Baseline Period 3 (Baseline 2) to End of Week 40 ] [ Designated as safety issue: No ]
    Treatment failure is defined as: 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at re-randomization (visit 13))/DSM-IV ADHD RS total score at re-randomization (visit 13) >= 30% AND 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at randomization (visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) > - 30%. The ADHD-RS-IV is an 180item clinician rated scale to assess ADHD by DSM-IV-TR, defined criteria using symptom terminology appropriate for the adult population. Each item pertains to inattention (odd-numbered) or hyperactivity/impulsivity (even-numbered) and is scored on a scale of 0 (no symptoms) to 3 (severe symptoms). A total added score can range from 0-54


Secondary Outcome Measures:
  • Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1 [ Time Frame: Baseline 1 to End of Period 1 (Week 9) ] [ Designated as safety issue: No ]
    On the CGI-I scale, a lower score reflects greater improvement between 1 and 3, a score of 4 is "no change", scores higher than 4 reflect worsening. The CGI-I consists of 7 ratings that range from 1 = "Very much improved" to 7 ="Very much worse". Improvement on the CGI-I scale is defined as a visit rating of 1 "very much improved" or 2 "much improved" on the CGI-I scale. Percentage has been calculated from the evaluable patients (N) as Percentage = n/N * 100.

  • Change From Baseline 1 in DSM-IVADHD RS Total Score, SDS Total Score, The Conners' Adult ADHD Rating Scale Observer Short Version (CAARS-O:S) Total Score and Adult Self-Report Scale (ASRS) Total Score at the End of Period 2 (Visit 13/ Week 14) [ Time Frame: Baseline 1 to End of Period 2 (Week 14) ] [ Designated as safety issue: No ]
    DSM-IV ADHD RS consists of 18 items directly adapted from the ADHD symptom list according to the DSM-IV. The SDS is a five-item, self-rated questionnaire that has been used widely in clinical trials and observational studies. CAARS-O: S consists of 26 items and 6 subscales: Inattention/Memory Problems, Hyperactivity/Restlessness, Impulsivity/Emotional Lability, Problems with Self-Concept, ADHD Index, and Inconsistency Index and is rated by someone close to the patient in their daily life such as a spouse, friend, or coworker. The Adult Self-Report Scale (ASRS) is a self-rating scale designed to assess Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. The 18 items are written to reflect the DSM-IV diagnostic criteria for ADHD and are rated from 0 ("Never") to 4 ("Very often").

  • Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14) [ Time Frame: Baseline 1 to End of Period 2 (Week 14) ] [ Designated as safety issue: No ]
    CGI-I assesses the overall change of illness relative to baseline. CGI-I consists of 7 ratings that range from 1 = "very much improved", 2 = "much improved", 3 = "minimally improved", 4 = "no change from baseline", 5 = "minimally worse", 6 = "much worse" 7 = "very much worse"

  • Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14) [ Time Frame: Baseline 1 to End of Period 2 (Week 14) ] [ Designated as safety issue: No ]
    CGI-S assesses the patient's current illness state. CGI-S consists of 7 ratings that range from 1 = "normal, not at all ill" , 2 = "borderline mentally ill", 3 =" mildly ill", 4 = "moderately ill", 5 = "markedly ill", 6 = "severely ill", 7 = "among the most extremely ill patients"

  • Change From Baseline Period 3 (Baseline 2) to End of Period 3 on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale ADHD RS Total Score by Treatment [ Time Frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) ] [ Designated as safety issue: No ]
    The ADHD-RS-IV is an 180 item clinician rated scale to assess ADHD by DSM-IV-TR, defined criteria using symptom terminology appropriate for the adult population. Each item pertains to inattention (odd-numbered) or hyperactivity/impulsivity (even-numbered) and is scored on a scale of 0 (no symptoms) to 3 (severe symptoms). A total added score can range from 0-54.

  • Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment [ Time Frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) ] [ Designated as safety issue: No ]
    The Sheehan Disability Scale (SDS) is a self-rating scale designed to assess the extent to which the patient's work social life/leisure activities and home life are impaired by his or her symptoms. The scale generates 4 scores: a work disability score, a social life disability score, a family life disability score and a total score. To get a total score the 3 individual scores (work: social life: family life) are totaled. The maximum possible score is 30 The higher the score, the more "impaired" a patient's work, social life, family life is.

  • Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment [ Time Frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) ] [ Designated as safety issue: No ]
    On the CGI-I scale, a lower score reflects greater improvement between 1 and 3, a score of 4 is "no change", scores higher than 4 reflect worsening. The CGI-I consists of 7 ratings that range from 1 = "Very much improved" to 7 ="Very much worse". Improvement on the CGI-I scale is defined as a visit rating of 1 "very much improved" or 2 "much improved" on the CGI-I scale.

  • Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment [ Time Frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) ] [ Designated as safety issue: No ]
    CGI-S assesses the patient's current illness state. CGI-S consists of 7 ratings that range from 1 = "normal, not at all ill" , 2 = "borderline mentally ill", 3 =" mildly ill", 4 = "moderately ill", 5 = "markedly ill", 6 = "severely ill", 7 = "among the most extremely ill patients"

  • Change From Baseline Period 3 (Baseline 2) to End of Period 3 in Conners Adult ADHD Rating Scales Observer: Short Version (CAARS-O:S:) Total Score by Treatment [ Time Frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) ] [ Designated as safety issue: No ]
    CAARS is an instrument to assess ADHD symptoms and behaviors in adults. This study utilizes the Observer Short Version (CAARS-O: S), consisting of 26 items and 6 subscales: Inattention/Memory Problems, Hyperactivity/Restlessness, Impulsivity/Emotional Lability, Problems with Self-Concept, ADHD Index (to distinguish ADHD adults from non-clinical adults), and Inconsistency Index (to identify random or careless responding) and is rated by someone close to the patient in their daily life such as a spouse, friend, or coworker. The observer is asked to notice the patient carefully and decide how much or how frequently each of the 26 items of the scale describes the patient recently. The response to every question in increasing order of severity is "not at all, never = 0; Just a little, once in a while = 1; Pretty much, often = 2; Very much, very frequently = 3". The total score combined from all the 26 items ranges from 0 to 88.

  • Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment [ Time Frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks) ] [ Designated as safety issue: No ]
    The ASRS is a self-rating scale designed to assess ADHD symptoms in adults and is now part of the World Health Organization Composite International Diagnostic Interview. It consists of 18 items written to reflect the DSM-IV diagnostic criteria for ADHD and are rated from 0 ("Never") to 4 ("Very often"). The total score ranges from 0 to 72.


Enrollment: 725
Study Start Date: November 2010
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ritalin LA 40 mg
In period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2, continued in same dose till week 9. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 40 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14. In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40.
Drug: Ritalin LA 20 mg
Ritalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 40, 60, or 80 mg.
Experimental: Ritalin LA 60 mg
In period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2 and to 60 mg at week 3. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 60 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14.In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40.
Drug: Ritalin LA 20 mg
Ritalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 40, 60, or 80 mg.
Drug: Ritalin LA 30 mg
Ritalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 60, or 80 mg.
Experimental: Ritalin LA 80 mg
In period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2 and to 60 mg at week 3 and to 80 mg at week 4. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 60 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14. In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40.
Drug: Ritalin LA 20 mg
Ritalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 40, 60, or 80 mg.
Drug: Ritalin LA 30 mg
Ritalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 60, or 80 mg.
Placebo Comparator: Placebo
Period 1- Placebo controlled Period 2 - The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose (40, 60 or 80 mg). In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40.
Drug: Placebo
Placebo Comparator: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Diagnosis of attention deficit/hyperactivity disorder (ADHD) which started in childhood
  2. Female patients of childbearing potential must be practicing an acceptable method of contraception.

Exclusion criteria:

  1. Patients with body mass index (BMI) less than 18.5 kg/m2 or more than 35 kg/m2
  2. History of alcohol or substance abuse within the last six months.
  3. History of seizures or use of anticonvulsant medication.
  4. Any psychiatric condition that requires medication or may interfere with study participation.
  5. Pre-existing cardiovascular disorders including severe hypertension, heart failure, myocardial infraction, etc.
  6. Significant respiratory, hepatic, gastrointestinal, renal, hematological or oncologic disorder
  7. Diagnosis of glaucoma, hyperthyroidism, pheochromocytoma
  8. Diagnosis or family history of Tourette's syndrome
  9. Pre-existing cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or stroke

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01259492

  Show 68 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01259492     History of Changes
Other Study ID Numbers: CRIT124D2302, 2010-021533-31
Study First Received: December 11, 2010
Results First Received: August 6, 2013
Last Updated: September 29, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Institute for Drugs and Medical Devices
Norway: Norwegian Medicines Agency
Denmark: Danish Medicines Agency
Sweden: Medical Products Agency
Singapore: Health Sciences Authority
South Africa: Medicines Control Council

Keywords provided by Novartis:
Attention Deficit /Hyperactivity Disorder, hyperactivity

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Disease
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Dyskinesias
Mental Disorders
Mental Disorders Diagnosed in Childhood
Nervous System Diseases
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Methylphenidate
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014