Lisdexamfetamine Dimesylate 2-year Safety Study in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01328756
First received: March 29, 2011
Last updated: July 9, 2015
Last verified: October 2014
Results First Received: May 15, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label
Condition: Attention Deficit Hyperactivity Disorder (ADHD)
Intervention: Drug: Lisdexamfetamine dimesylate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study enrolled participants from 3 antecedent studies (SPD489-317 [NCT01106430], SPD489-325 [NCT00763971], and SPD489-326 [NCT00784654]), or directly enrolled.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
If participants from previous SDP489 studies had a gap of more than 7 days before participation in this study, they were required to have baseline Attention-Deficit/Hyperactivity Disorder (ADHD) total score of at least 28, to be enrolled. Of 348 participants screened, 314 participants were enrolled and treated.

Reporting Groups
  Description
Lisdexamfetamine Dimesylate

Lisdexamfetamine dimesylate (SPD489) 30, 50 and 70 milligram (mg) capsules once daily orally during the 4-week dose optimization period and the 100-week maintenance period.

At optimization period, participants started SPD489 30 mg and dose was titrated until acceptable response (30% reduction from baseline in ADHD Rating Scale-IV total score, clinical global impression-improvement [CGI-I]score of 1 or 2 with tolerable side effects) was achieved. Maximum dose was 70mg. Dose adjustments were done in dose maintenance period.


Participant Flow:   Overall Study
    Lisdexamfetamine Dimesylate  
STARTED     314  
COMPLETED     191  
NOT COMPLETED     123  
Protocol Violation                 4  
Adverse Event                 39  
Lack of Efficacy                 5  
Withdrawal by Subject                 41  
Lost to Follow-up                 5  
Unspecified                 29  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Lisdexamfetamine Dimesylate Lisdexamfetamine dimesylate (SPD489) 30, 50 and 70 mg capsules once daily orally during the 4-week dose optimization period and the 100-week maintenance period.

Baseline Measures
    Lisdexamfetamine Dimesylate  
Number of Participants  
[units: participants]
  314  
Age  
[units: years]
Mean (Standard Deviation)
  11.4  (2.88)  
Gender  
[units: participants]
 
Female     64  
Male     250  
Clinical Global Impressions – Severity of Illness (CGI-S) Rating [1]
[units: participants]
 
Normal, not all ill     0  
Borderline mentally ill     0  
Mildly ill     1  
Moderately ill     69  
Markedly ill     152  
Severely ill     81  
Among the most extremely ill participants     11  
Body Weight  
[units: kilogram(s)]
Mean (Standard Deviation)
  46.13  (16.434)  
Height  
[units: centimeters]
Mean (Standard Deviation)
  152.29  (16.633)  
Body Mass Index (BMI) [2]
[units: kilogram per square meter]
Mean (Standard Deviation)
  19.22  (3.389)  
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV): Total Score [3]
[units: scores on a scale]
Mean (Standard Deviation)
  41.1  (7.03)  
ADHD-RS-IV: Inattention Subscale Score [4]
[units: scores on a scale]
Mean (Standard Deviation)
  22.1  (3.52)  
ADHD-RS-IV: Hyperactivity/Impulsivity Subscore [5]
[units: scores on a scale]
Mean (Standard Deviation)
  19  (5.86)  
[1] The Clinical Global Impressions (CGI) Scale permits a global evaluation of the participant’s severity and improvement over time. This assessment will help guide the clinician on dosing adjustments. The CGI has been used extensively in clinical studies of ADHD. CGI-S was a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants), evaluated by the Investigator.
[2] BMI was calculated as (weight [kilogram] per height [square meter]) at screening.
[3] ADHD-RS-IV consisted of 18 items designed to reflect current symptomatology of ADHD based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition – Text Revision (DSM-IV-TR) criteria, completed by the Investigator. Each item was scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items were grouped into 2 sub-scales: hyperactivity/impulsivity (even number items 2-18 with score range of 0 to 27) and inattention (odd number items 1-17 with score range of 0 to 27). Higher scores depicted worse symptoms.
[4] ADHD-RS-IV consisted of 18 items designed to reflect current symptomatology of ADHD based on DSM-IV-TR criteria, completed by the Investigator. Each item was scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items were grouped into 2 sub-scales: hyperactivity/impulsivity and inattention. Inattention subscale score consisted of odd number items 1-17 with scores ranging from 0 to 27. Higher score indicated worse symptom.
[5] ADHD-RS-IV consisted of 18 items designed to reflect current symptomatology of ADHD based on DSM-IV-TR criteria, completed by the Investigator. Each item was scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items were grouped into 2 sub-scales: hyperactivity/impulsivity and inattention. Hyperactivity/impulsivity subscale score consisted of even number items 2-18 with scores ranging from 0 to 27. Higher score indicated worse symptom.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With All Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs   [ Time Frame: Baseline up to 3 days after the last dose of study treatment (up to 2 years) ]

2.  Primary:   Change From Baseline in Pulse Rate at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

3.  Primary:   Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

4.  Primary:   Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

5.  Primary:   Change From Baseline in Body Weight at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

6.  Primary:   Change From Baseline in Height at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

7.  Primary:   Change From Baseline in Body Mass Index (BMI) at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

8.  Primary:   Change From Baseline in Heart Rate at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

9.  Primary:   Change From Baseline in QT Interval at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

10.  Primary:   Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

11.  Primary:   Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRSC) Total Scores at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

12.  Secondary:   Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Total Score at Last On-treatment Assessment (LOTA)   [ Time Frame: Baseline (Week 0), LOTA (Week 104) ]

13.  Secondary:   Number of Participants With Clinical Global Impression-Global Improvement (CGI-I) at Last On-treatment Assessment (LOTA)   [ Time Frame: LOTA (Week 104) ]

14.  Secondary:   Number of Participants With Clinical Global Impression-Severity of Illness (CGI-S) at Last On-treatment Assessment (LOTA)   [ Time Frame: LOTA (Week 104) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Since this study is an open-label trial, results should be interpreted with caution.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Physician
Organization: Shire
phone: 1 866-842-5335


No publications provided


Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01328756     History of Changes
Obsolete Identifiers: NCT01413165
Other Study ID Numbers: SPD489-404, 2010-020951-30
Study First Received: March 29, 2011
Results First Received: May 15, 2015
Last Updated: July 9, 2015
Health Authority: United States: Food and Drug Administration