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

Attention Deficit/Hyperactivity Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01259492
• Other study ID #: CRIT124D2302
• Secondary ID: 2010-021533-31
• Status: Completed
• Phase: Phase 3
• First received: December 11, 2010
• Last updated: September 29, 2014
• Start date: November 2010
• Est. completion date: August 2012

Study information

• Verified date: September 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosBelgium: Federal Agency for Medicinal Products and Health ProductsGermany: Institute for Drugs and Medical DevicesNorway: Norwegian Medicines AgencyDenmark: Danish Medicines AgencySweden: Medical Products AgencySingapore: Health Sciences AuthoritySouth Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 725
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Placebo
Placebo Comparator: Placebo
• 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.
• 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.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Heusden-Zolder
Belgium	Novartis Investigative Site	Kessel-Lo
Belgium	Novartis Investigative Site	Kortenberg
Belgium	Novartis Investigative Site	Mechelen
Belgium	Novartis Investigative Site	Uccle
Colombia	Novartis Investigative Site	Antioquia
Colombia	Novartis Investigative Site	Antioquia
Colombia	Novartis Investigative Site	Bogotá
Denmark	Novartis Investigative Site	Århus C
Germany	Novartis Investigative Site	Ahrensburg
Germany	Novartis Investigative Site	Bamberg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Ellwangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Hagen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Landau
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Limburg
Germany	Novartis Investigative Site	Ludwigsburg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Naumburg
Germany	Novartis Investigative Site	Nürnberg
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Westerstede/Oldenburg
Germany	Novartis Investigative Site	Wolfsburg
Germany	Novartis Investigative Site	Würzburg
Norway	Novartis Investigative Site	Porsgrunn
Norway	Novartis Investigative Site	Skien
Singapore	Novartis Investigative Site	Singapore
South Africa	Novartis Investigative Site	Benoni
South Africa	Novartis Investigative Site	Melrose Arch
South Africa	Novartis Investigative Site	Pretoria
Sweden	Novartis Investigative Site	Luleå
Sweden	Novartis Investigative Site	Malmö
Sweden	Novartis Investigative Site	Stockholm
United States	Novartis Investigative Site	Bellevue	Washington
United States	Novartis Investigative Site	Beverly Hills	California
United States	Novartis Investigative Site	Bradenton	Florida
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Fargo	North Dakota
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Libertyville	Illinois
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Owensboro	Kentucky
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Spring Valley	California
United States	Novartis Investigative Site	Troy	Michigan
United States	Novartis Investigative Site	West Plam Beach	Florida
United States	Novartis Investigative Site	Willingboro	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Colombia,  Denmark,  Germany,  Norway,  Singapore,  South Africa,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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%.	Baseline 1 to End of Period 1 (Week 9)	No
Primary	Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment	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.	Baseline 1 to End of Period 1 (Week 9)	No
Primary	Percentage of Participants With Treatment Failures During Period 3	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	Baseline Period 1 (Baseline 1) and Baseline Period 3 (Baseline 2) to End of Week 40	No
Secondary	Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1	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.	Baseline 1 to End of Period 1 (Week 9)	No
Secondary	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)	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").	Baseline 1 to End of Period 2 (Week 14)	No
Secondary	Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14)	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"	Baseline 1 to End of Period 2 (Week 14)	No
Secondary	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)	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"	Baseline 1 to End of Period 2 (Week 14)	No
Secondary	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	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.	Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)	No
Secondary	Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment	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.	Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)	No
Secondary	Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment	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.	Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)	No
Secondary	Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment	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"	Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)	No
Secondary	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	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.	Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)	No
Secondary	Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment	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.	Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)	No