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

NCT01259492 | Completed Phase 3 Results

• 2 other identifiers: CRIT124D23022010-021533-31
• Study Type: interventional
• Target: 725
• Locations: 9 countries
• Sites: 68

Brief 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).

Conditions

Attention Deficit/Hyperactivity Disorder

Keywords

Attention Deficit /Hyperactivity Disorder, hyperactivity

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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

Secondary Outcomes (10)

• Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1

  Baseline 1 to End of Period 1 (Week 9)

• 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)

  Baseline 1 to End of Period 2 (Week 14)

• Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14)

  Baseline 1 to End of Period 2 (Week 14)

• 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)

  Baseline 1 to End of Period 2 (Week 14)

• 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

  Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)

Study Arms (4)

Ritalin LA 40 mg

EXPERIMENTAL

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 60 mg

EXPERIMENTAL

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; Drug: Ritalin LA 30 mg

Ritalin LA 80 mg

EXPERIMENTAL

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; Drug: Ritalin LA 30 mg

Placebo

PLACEBO COMPARATOR

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

Interventions

Placebo DRUG

Placebo Comparator: Placebo

Placebo

Ritalin LA 20 mg DRUG

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 40 mg; Ritalin LA 60 mg; Ritalin LA 80 mg

Ritalin LA 30 mg DRUG

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.

Ritalin LA 60 mg; Ritalin LA 80 mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (68)

Novartis Investigative Site

Little Rock, Arkansas, 72205, United States

Location

Novartis Investigative Site

Beverly Hills, California, 90210, United States

Location

Novartis Investigative Site

Spring Valley, California, 91978-1522, United States

Location

Novartis Investigative Site

Bradenton, Florida, 34208, United States

Location

Novartis Investigative Site

Miami, Florida, 33173, United States

Location

Novartis Investigative Site

Orlando, Florida, 32806, United States

Location

Novartis Investigative Site

West Plam Beach, Florida, 33407, United States

Location

Novartis Investigative Site

Libertyville, Illinois, 60048, United States

Location

Novartis Investigative Site

Owensboro, Kentucky, 42301, United States

Location

Novartis Investigative Site

Troy, Michigan, 48083, United States

Location

Novartis Investigative Site

Las Vegas, Nevada, 89119, United States

Location

Novartis Investigative Site

Las Vegas, Nevada, 89128, United States

Location

Novartis Investigative Site

Willingboro, New Jersey, 08046, United States

Location

Novartis Investigative Site

Fargo, North Dakota, 58103, United States

Location

Novartis Investigative Site

Columbus, Ohio, 43210, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73112, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19149, United States

Location

Novartis Investigative Site

Houston, Texas, 77007, United States

Location

Novartis Investigative Site

Houston, Texas, 77008, United States

Location

Novartis Investigative Site

Bellevue, Washington, 98004, United States

Location

Novartis Investigative Site

Seattle, Washington, 98104, United States

Location

Novartis Investigative Site

Bruges, Belgium, 8310, Belgium

Location

Novartis Investigative Site

Heusden-Zolder, Belgium, 3550, Belgium

Location

Novartis Investigative Site

Kortenberg, Belgium, 3070, Belgium

Location

Novartis Investigative Site

Uccle, Belgium, 1180, Belgium

Location

Novartis Investigative Site

Kessel-Lo, 3010, Belgium

Location

Novartis Investigative Site

Mechelen, 2800, Belgium

Location

Novartis Investigative Site

Santa Fe de Antioquia, Antioquia, 0000, Colombia

Location

Novartis Investigative Site

Antioquia, Colombia

Location

Novartis Investigative Site

Bogotá, Colombia

Location

Novartis Investigative Site

Århus C, 8000, Denmark

Location

Novartis Investigative Site

Ahrensburg, Germany, 22926, Germany

Location

Novartis Investigative Site

Bamberg, Germany, 96047, Germany

Location

Novartis Investigative Site

Berlin, Germany, 12200, Germany

Location

Novartis Investigative Site

Essen, Germany, 45147, Germany

Location

Novartis Investigative Site

Hamburg, Germany, 20259, Germany

Location

Novartis Investigative Site

Kiel, Germany, 24105, Germany

Location

Novartis Investigative Site

Ludwigsburg, Germany, 71636, Germany

Location

Novartis Investigative Site

Mainz, Germany, 55131, Germany

Location

Novartis Investigative Site

München, Germany, 80333, Germany

Location

Novartis Investigative Site

Naumburg, Germany, 06618, Germany

Location

Novartis Investigative Site

Nuremberg, Germany, 90419, Germany

Location

Novartis Investigative Site

Wolfsburg, Germany, 38444, Germany

Location

Novartis Investigative Site

Berlin, 10629, Germany

Location

Novartis Investigative Site

Dresden, 01129, Germany

Location

Novartis Investigative Site

Ellwangen, 73479, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79104, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Hagen, 58093, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Homburg, 66421, Germany

Location

Novartis Investigative Site

Landau, 76829, Germany

Location

Novartis Investigative Site

Leipzig, 04157, Germany

Location

Novartis Investigative Site

Limburg, 65549, Germany

Location

Novartis Investigative Site

Mannheim, 68159, Germany

Location

Novartis Investigative Site

Siegen, 57076, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Westerstede/Oldenburg, 26655, Germany

Location

Novartis Investigative Site

Würzburg, 97070, Germany

Location

Novartis Investigative Site

Porsgrunn, Norway, 3922, Norway

Location

Novartis Investigative Site

Skien, 3725, Norway

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Benoni, South Africa

Location

Novartis Investigative Site

Melrose Arch, 2196, South Africa

Location

Novartis Investigative Site

Pretoria, 0001, South Africa

Location

Novartis Investigative Site

Luleå, 972 35, Sweden

Location

Novartis Investigative Site

Malmo, 211 53, Sweden

Location

Novartis Investigative Site

Stockholm, 141 86, Sweden

Location

Related Publications (1)

• Huss M, Ginsberg Y, Tvedten T, Arngrim T, Philipsen A, Carter K, Chen CW, Kumar V. Methylphenidate hydrochloride modified-release in adults with attention deficit hyperactivity disorder: a randomized double-blind placebo-controlled trial. Adv Ther. 2014 Jan;31(1):44-65. doi: 10.1007/s12325-013-0085-5. Epub 2013 Dec 27.

  PMID: 24371021 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

8627788300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2010
• First Posted: December 14, 2010
• Study Start: November 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 7, 2014
• Results First Posted: April 29, 2014

Record last verified: 2014-09

Locations

NO (2); ZA (3); BE (6); SE (3); DK (1); SG (1); DE (28); US (21); CO (3)