An Efficacy and Safety Study of Osmotic Release Oral System (OROS) Methylphenidate in Participants With Attention Deficit Hyperactivity Disorder (ADHD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier:
NCT01012622
First received: November 5, 2009
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to evaluate the safety and efficacy of Osmotic Release Oral System (OROS) methylphenidate in participants with Attention Deficit Hyperactivity Disorder (ADHD).


Condition Intervention Phase
Attention Deficit Disorder With Hyperactivity
Drug: Osmotic Release Oral System (OROS) Methylphenidate Hydrochloride
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Prospective Trial to Evaluate Functional Outcomes of OROS Methylphenidate in Children With ADHD (FOSCO)

Resource links provided by NLM:


Further study details as provided by Janssen Korea, Ltd., Korea:

Primary Outcome Measures:
  • Change From Baseline in Korean Version of the Attention-Deficit Hyperactivity Disorder (K-ADHD) Rating Scale (K-ARS) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    K-ARS measures the 18 symptoms based on Diagnostic and Statistical Manual of Mental Disorders-forth edition (DSM-IV 1994). Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often), whereas the rating of 2 points or more was regarded as abnormal. Total scores range from 0 (no symptoms) to 54 (highly symptomatic), higher score indicates worsening of condition.

  • Number of Participants With Response Based on K-ARS Total Score at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Response is defined as at least 25 percent (%) decrease in total score of K-ARS compared to baseline. K-ARS measures the 18 symptoms based on DSM-IV (1994). Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often), whereas the rating of 2 points or more was regarded as abnormal. Total scores range from 0 (no symptoms) to 54 (highly symptomatic), higher score indicates worsening of condition.

  • Number of Participants With Remission Based on K-ARS Total Score and Clinical Global Impression - Improvement (CGI-I) Scale Score at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Remission is defined by all of the following criteria; 1) K-ARS Total score of 18 or less. 2) "Very much improved" or "Much improved" in CGI-I. K-ARS total score ranges from 0 (no symptoms) to 54 (highly symptomatic), higher score indicates worsening of condition. CGI-I is a 7-point scale ranging from 1 to 7, where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse, higher score indicates worsening of condition.


Secondary Outcome Measures:
  • Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CHIP was designed to assess the physical, psychological health conditions and functional well-being of children. The instrument has sub-domains such satisfaction (11 items) ranges from 0 to 44, stability (22 items) ranges from 0 to 88, elasticity (19 items) ranges from 0 to 76, risk aversion (14 items) ranges from 0 to 56, achievement (10 items) ranges from 0 to 40. Good health is in the range from 44 to 56 points for all sub-domains. A score of 43 or below indicates poor health in that domain. A score of 57 or higher indicates excellent health. The total score is an average of the scores for the 5 domains and ranges from 0 to 304. Higher total score indicates better health.

  • Change From Baseline in Visual Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CAT was developed to properly reflect brain function in childhood. It provided measurement of simple visual selective attention in terms of omission (number of missing response to target stimulus [0-150], higher score indicate greater omission), false alarm (number of response to non-target stimulus [0-150], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus [200-1100, low score means faster response to target stimulus]), Response (consistency of response time to target stimulus [30-650, Low score means good consistency of response]).

  • Change From Baseline in Auditory Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CAT was developed to properly reflect brain function in childhood. It provided measurement of simple auditory selective attention in terms of omission (number of missing response to target stimulus [0-150], higher score indicate greater omission), false alarm (number of response to non-target stimulus [0-150], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus [200-1100, low score means faster response to target stimulus]), Response (consistency of response time to target stimulus [30-650, Low score means good consistency of response]).

  • Change From Baseline in Inhibition-Sustained Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CAT was developed to properly reflect brain function in childhood. It provided measurement of simple inhibition-sustained attention in terms of omission(number of missing response to target stimulus [0-150], higher score indicate greater omission), false alarm(number of response to non-target stimulus [0-150], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus [200-1100, low score means faster response to target stimulus]), Response (consistency of response time to target stimulus [30-650, Low score means good consistency of response]).

  • Change From Baseline in Interference-Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CAT was developed to properly reflect brain function in childhood. It provided measurement of simple interference-selective attention in terms of omission(number of missing response to target stimulus[0-150], higher score indicate greater omission), false alarm(number of response to non-target stimulus[0-150], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus [200-1100, low score means faster response to target stimulus]), Response (consistency of response time to target stimulus [30-650, Low score means good consistency of response]).

  • Change From Baseline in Divided Attention Subtest of Comprehensive Attention Test (CAT) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CAT was developed to properly reflect brain function in childhood. It provided measurement of simple divided attention in terms of omission(number of missing response to target stimulus[0-150], higher score indicate greater omission), false alarm(number of response to non-target stimulus[0-150], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus [200-1100, low score means faster response to target stimulus]), Response (consistency of response time to target stimulus [30-650, Low score means good consistency of response]).

  • Change From Baseline in Working Memory Forward Subtest of Comprehensive Attention Test (CAT) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CAT was developed to properly reflect brain function in childhood. The test battery provided a comprehensive measurement of simple visual auditory attention, interventional visual-auditory selective attention, divided attention, continuous attention, and operational memory. Working memory forward was measured in terms of width of space and number of correct responses ranging from 0 to 10. For width of space boxes were presented on the screen and participants remembered the order of presented box. Participants pressed the box using mouse in the forward order. Maximum number that participants correctly memorized box in the screen in the respective order was reported and overall number of times a participant responded correctly was also reported.

  • Change From Baseline in Working Memory Backward Subtest of Comprehensive Attention Test (CAT) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CAT was developed to properly reflect brain function in childhood. The test battery provided a comprehensive measurement of simple visual auditory attention, interventional visual-auditory selective attention, divided attention, continuous attention, and operational memory. Working memory forward was measured in terms of width of space and number of correct responses ranging from 0 to 10. For width of space boxes were presented on the screen and participants remembered the order of presented box. Participants pressed the box using mouse in the backward order. Maximum number that participants correctly memorized box in the screen in the respective order was reported and overall number of times a participant responded correctly was also reported.

  • Change From Baseline in Academic Performance Rating Scale (APRS) Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    APRS scale measures four factors in elementary school children such as learning ability, academic performance, impulse control, and social withdrawal. In particular, it is excellent in assessing drug effect on the academic performance not measured by other scales. Score ranges from 19 to 95, higher score means better academic performance.

  • Change From Baseline in Beck Depression Inventory (BDI) Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Beck Depression Inventory (BDI) consisted of 21 items for measuring the subjective severity of depression and emotional, cognitive, motivational, physiological symptoms of depression. Each question has a set of 4 possible answer choices, ranging in intensity, each answer being scored on a scale value of 0 (no symptom) to 3 (the most severe symptom). Accordingly, the total score ranges from 0 (no symptom) to 63 (the most severe symptom) for 21 questions.

  • Change From Baseline in Parenting Stress Index (PSI) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Parenting Stress Index (PSI) was designed to assess parent or guardian child-rearing stress index on a 5-rating scale from "never" to "very truly". Out of 30 items, 20 items are scored, being consisted of 8 child characteristics-related stress items; 9 parent-child interaction-related stress items; and 3 achievement expectation-related stress items. A possible total score ranges from 20 to 100; Increase in score indicates higher stress perceived by the parent.

  • Change From Baseline in Clinical Global Impression-severity (CGI-S) Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher change scores indicate worsening.

  • Clinical Global Impression - Improvement (CGI-I) Scale Score at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Improved very much, Improved much and Improved a little are defined as improvement and No change, Aggravated a little, Aggravated much and Aggravated very much were defined as aggravation.


Enrollment: 142
Study Start Date: September 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OROS Methylphenidate Hydrochloride Drug: Osmotic Release Oral System (OROS) Methylphenidate Hydrochloride
OROS methylphenidate hydrochloride (HCL) will be given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose will be increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.

Detailed Description:

This is an open-label (all people involved know the identity of the intervention), single arm, multicenter (when more than one hospital or medical school team work on a medical research study), prospective study (study following participants forward in time) to evaluate the efficacy and safety of OROS methylphenidate in participants with ADHD (behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity). The study duration will be of 12 weeks per participant, which is divided into 2 parts Screening (within 14 days before study commences on Day -1) and treatment (8 weeks and will include titration period [from the initiation of the study treatment to determination of the individual's maintenance dose] and maintenance period [at least 4 weeks after determination of maintenance dose]). Participants will receive initial dose depending on their body weight. OROS methylphenidate hydrochloride (HCL) will be given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose will be increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability. Efficacy will be evaluated by Korean Version, ADHD Rating Scale (K-ARS) total score and Clinical Global Impression)-Severity / Impression rating scale CGI-S/I. Participants safety will be monitored throughout the trial.

  Eligibility

Ages Eligible for Study:   6 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants voluntarily provided informed consent to participate in the study
  • Participants with written informed consent to participate in the study voluntarily by caregivers/legal representatives
  • Participants who were capable to follow the study visit schedule well and their parents/caregivers who were willing to complete the assessments specified in the protocol and were capable to complete them
  • Participant and his/her parent/guardian able to understand the study participation and to request withdrawal from the study voluntarily at any time
  • Participants who were satisfied in diagnosis of Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) Attention Deficit Hyperactivity Disorder (ADHD) and determined to require drug therapy

Exclusion Criteria:

  • Participants who have known hypersensitivity (altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen) to methylphenidate HCL
  • Participants who have significant suicidal ideation
  • Participants with mental retardation
  • Participants who meet DSM-IV diagnostic criteria for current major depressive disorder or anxiety disorder requiring drug therapy
  • Participants who have abnormalities in the Electrocardiography (ECG) or show clinically significant abnormalities of laboratory results, including serum chemistries and hematology
  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: NCT01012622

Sponsors and Collaborators
Janssen Korea, Ltd., Korea
Investigators
Study Director: Janssen Korea, Ltd. Clinical Trial Janssen Korea, Ltd.
  More Information

No publications provided by Janssen Korea, Ltd., Korea

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier: NCT01012622     History of Changes
Other Study ID Numbers: CR015481, CON-KOR-4020
Study First Received: November 5, 2009
Results First Received: April 30, 2013
Last Updated: February 17, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Janssen Korea, Ltd., Korea:
Attention Deficit Hyperactivity Disorder
Methylphenidate Hydrochloride

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

ClinicalTrials.gov processed this record on August 01, 2014