Clinical Trial Results:
The Effective and Tolerable Titration Scheme and Dosage in Children with Attention-deficit hyperactivity disorder Treated with Osmotic controlled-release oral delivery system (OROS)-Methylphenidate
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Summary
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EudraCT number |
2015-001070-18 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
28 Jun 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Jul 2016
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First version publication date |
16 Jul 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
42603ATT4040
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00518232 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Janssen-Cilag Taiwan
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Sponsor organisation address |
8th Floor, #319, Section 2, Tunhwa South Road, Taipei 106, Taiwan,
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Public contact |
Clinical Registry Group-JB BV, Janssen Research and Development, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group-JB BV, Janssen Research and Development, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Jun 2007
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Jun 2007
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of the study is to investigate the clinical benefit of switching children with ADHD (attention deficit/hyperactive disorder) from immediate-release methylphenidate (IR-MPH) to Osmotic controlled-release oral delivery system (OROS)-methylphenidate under the correct dosage conversion scheme.
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Protection of trial subjects |
Safety was evaluated based on the following variables: adverse events and serious adverse events, measurement of vital signs and the performance of physical examinations. Barkley’s Side Effect Rating Scale (Barkley’s SERS) was used to measure side effects.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Sep 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Taiwan: 507
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Worldwide total number of subjects |
507
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
364
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Adolescents (12-17 years) |
143
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted from 18 September 2006 to 28 June 2007 and recruited subjects from 6 clinical centers. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
Total 521 subjects were enrolled in the study and 439 subjects completed the study. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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OROS Methylphenidate | ||||||||||||||||||||
Arm description |
Subjects receiving IR-MPH therapy at daily dosage of less than or equal to (<=) 15 milligram (mg) per day, were switched to receive OROS methylphenidate 18mg once daily orally up to 6 weeks. Subjects receiving IR-MPH therapy at a daily dosage of greater than >15 mg per day and <=30 mg per day, received OROS methylphenidate 36 mg once daily orally up to 6 weeks. Subjects receiving IR-MPH >30 mg per day, received OROS methylphenidate 54 mg once daily orally up to 6 weeks. Dose of OROS methylphenidate was up titrated or down titrated based on the optimal response and adverse event. The maximum daily dose of OROS methylphenidate was 54 mg per day. The final titration dose of OROS methylphenidate was continued for next 4 weeks. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
OROS Methylphenidate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
OROS Methylphenidate in a dose of 18 mg or 36 mg or 54 mg once daily orally.
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Baseline characteristics reporting groups
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Reporting group title |
OROS Methylphenidate
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Reporting group description |
Subjects receiving IR-MPH therapy at daily dosage of less than or equal to (<=) 15 milligram (mg) per day, were switched to receive OROS methylphenidate 18mg once daily orally up to 6 weeks. Subjects receiving IR-MPH therapy at a daily dosage of greater than >15 mg per day and <=30 mg per day, received OROS methylphenidate 36 mg once daily orally up to 6 weeks. Subjects receiving IR-MPH >30 mg per day, received OROS methylphenidate 54 mg once daily orally up to 6 weeks. Dose of OROS methylphenidate was up titrated or down titrated based on the optimal response and adverse event. The maximum daily dose of OROS methylphenidate was 54 mg per day. The final titration dose of OROS methylphenidate was continued for next 4 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
OROS Methylphenidate
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Reporting group description |
Subjects receiving IR-MPH therapy at daily dosage of less than or equal to (<=) 15 milligram (mg) per day, were switched to receive OROS methylphenidate 18mg once daily orally up to 6 weeks. Subjects receiving IR-MPH therapy at a daily dosage of greater than >15 mg per day and <=30 mg per day, received OROS methylphenidate 36 mg once daily orally up to 6 weeks. Subjects receiving IR-MPH >30 mg per day, received OROS methylphenidate 54 mg once daily orally up to 6 weeks. Dose of OROS methylphenidate was up titrated or down titrated based on the optimal response and adverse event. The maximum daily dose of OROS methylphenidate was 54 mg per day. The final titration dose of OROS methylphenidate was continued for next 4 weeks. | ||
Subject analysis set title |
Intent-to-treat (ITT) population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Subject analysis set description: Intent to treat (ITT) population included all enrolled subjects who received study drug and participated in at least one post-baseline evaluation.
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Subject analysis set title |
Efficacy Population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Efficacy population included all enrolled subjects who received study drug and completed the 10 week study duration.
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Subject analysis set title |
Safety analysis Set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety analysis set included all enrolled subjects who received study drug and participated on at least one post-baseline evaluation.
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End point title |
Percentage of Subjects With Optimal Response at Week 10 [1] | ||||||||
End point description |
Optimal response is defined as a score of 0 or 1 on each of the first 18 Attention-deficit/hyperactivity disorder (ADHD) items in Swanson, Nolan and Pelham-Fourth Edition (SNAP-IV) rating scale. SNAP-IV rating scale consists of 18 ADHD items and 8 Oppositional Defiant Disorder (ODD) items. Each item was scored for severity on a 4-point scale ranging from 0-3, where 0=not at all and 3=very much.
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End point type |
Primary
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End point timeframe |
Week 10
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not reported for this endpoint as inferential analysis was not planned. |
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| Notes [2] - ITT Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Optimal Response as per the Dose of OROS Methylphenidate [3] | ||||||||||||||
End point description |
Subjects with optimal response as per dose of OROS methylphenidate (18, 36 and 54 mg per day) were reported. Optimal response is defined as a score of 0 or 1 on each of the first 18 Attention- deficit/hyperactivity disorder (ADHD) items in Swanson, Nolan and Pelham-Fourth Edition (SNAP-IV) rating scale. SNAP-IV rating scale consists of 18 ADHD items and 8 Oppositional Defiant Disorder (ODD) items. Each item was scored for severity on a 4-point scale ranging from 0-3, where 0=not at all and 3=very much.
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End point type |
Primary
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End point timeframe |
Up to Week 10
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not reported for this endpoint as inferential analysis was not planned. |
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| Notes [4] - ITT Population |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change from Baseline in Swanson, Nolan, and Pelham Questionnaire (SNAP-IV) Total Score at Week 10 | ||||||||||||
End point description |
SNAP-IV rating scale consists of 18 ADHD items and 8 Oppositional Defiant Disorder (ODD) items. Each item was scored for severity on a 4-point scale ranging from 0-3, where 0=not at all and 3=very much.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 10
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| Notes [5] - Efficacy population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Clinical Global Impression (CGI) Scale Score | ||||||||||||||||
End point description |
The Clinical Global Impression Severity (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 scores indicate worsening. CGI Improvement scale is a 7 point scale that requires the clinician to assess how much the subject’s illness has improved or worsened relative to a baseline state at the beginning of the intervention: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 10
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| Notes [6] - Efficacy Population |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Global Satisfaction at Week 10 | ||||||||||||||||
End point description |
Global satisfaction included ratings from parent/caregiver, subjects/patients rationings, observations during study period and adverse effects. This scale ranges from 1=completely dissatisfied to 5=complete satisfied.Global satisfaction was assessed by parent/caregiver and subject.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 10
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| Notes [7] - Efficacy population |
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to end of treatment (week 10)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
OROS Methylphenidate
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Reporting group description |
Subjects receiving IR-MPH therapy at daily dosage of less than or equal to (<=) 15 milligram (mg) per day, were switched to receive OROS methylphenidate 18mg once daily orally up to 6 weeks. Subjects receiving IR-MPH therapy at a daily dosage of greater than >15 mg per day and <=30 mg per day, received OROS methylphenidate 36 mg once daily orally up to 6 weeks. Subjects receiving IR-MPH >30 mg per day, received OROS methylphenidate 54 mg once daily orally up to 6 weeks. Dose of OROS methylphenidate was up titrated or down titrated based on the optimal response and adverse event. The maximum daily dose of OROS methylphenidate was 54 mg per day. The final titration dose of OROS methylphenidate was continued for next 4 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
