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Trial record 36 of 592 for:    binge eating disorder

Evaluate the Maintenance of Efficacy of SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder

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ClinicalTrials.gov Identifier: NCT02009163
Recruitment Status : Completed
First Posted : December 11, 2013
Results First Posted : April 1, 2016
Last Update Posted : April 1, 2016
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Binge Eating Disorder
Interventions Drug: Lisdexamfetamine dimesylate
Other: Placebo
Enrollment 418
Recruitment Details  
Pre-assignment Details  
Arm/Group Title SPD489 (Open-label Period) Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description SPD489 treatment was taken orally once daily at approximately 7:00 AM. All participants began treatment with SPD489 at the lowest dose level (30mg) during the 4-week open-label dose-optimization period. After 1 week of treatment at 30mg, all participants were titrated to the next dose level (50mg). After 1 week of treatment at 50mg, all participants were titrated to the highest dose level (70mg), as tolerated and as clinically indicated. After 1 week of treatment at the highest dose, the participant could have been down-titrated to 50mg; no further dose adjustments were permitted. The optimal daily dose of 50 or 70mg achieved during dose-optimization was maintained throughout the 8-week dose-maintenance period. The total time of the open-label period was 12 weeks. During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week. For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26­week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Period Title: Open-label Period (Non-randomized)
Started 418 0 0
Completed 275 0 0
Not Completed 143 0 0
Reason Not Completed
Failure to Meet Randomization Criteria             48             0             0
Withdrawal by Subject             29             0             0
Adverse Event             22             0             0
Lost to Follow-up             20             0             0
Protocol Violation             10             0             0
Pregnancy             1             0             0
Not specified             13             0             0
Period Title: Randomized-withdrawal Period
Started 0 [1] 138 [2] 137 [2]
Completed 0 50 102
Not Completed 0 88 35
Reason Not Completed
Withdrawal by Subject             0             25             9
Lost to Follow-up             0             13             6
Adverse Event             0             0             6
Relapse Criteria Met             0             40             5
Protocol Violation             0             1             2
Pregnancy             0             0             2
Not specified             0             9             5
[1]
The open-label treatment group is not an arm of the randomized-withdrawal period.
[2]
The total who started the Placebo and SPD489 arms equals those who completed the open-label period.
Arm/Group Title Open-label Safety Population
Hide Arm/Group Description The Open-label Safety Population included all participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment.
Overall Number of Baseline Participants 411
Hide Baseline Analysis Population Description
The Open-label Safety Population (OSP) was defined as all participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment. Seven participants were enrolled but not treated and thus not included in the OSP.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 411 participants
38.3  (10.40)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 411 participants
< 40 years of age 217
>/= 40 years of age 194
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 411 participants
Female
358
  87.1%
Male
53
  12.9%
1.Primary Outcome
Title Time to Relapse From Date of Randomization to Endpoint of The Randomized-withdrawal Period
Hide Description Relapse status was assessed during the double-blind treatment phase and was defined as having 2 or more binge days per week for 2 consecutive weeks (14 consecutive days) prior to any visit and having an increase in Clinical Global Impressions-Severity (CGI-S) score of 2 or more points compared to the randomized-withdrawal baseline (date of relapse – date of randomization). Binge eating information was captured via a self-report paper diary. The binge diary captured the number of binges per day, total hours per day spent binging, type of binge (at mealtime or at another time other than mealtime), and a description of the binge (amounts and types of foods). Binge frequency was reviewed by the clinician with the subject to confirm reported binge episodes per day. The CGI-S was performed to rate the severity of a subject’s condition using a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill).
Time Frame Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS): participants in the Randomized Safety Analysis Set (RSAS) with at least 1 post-randomization CGI-S assessment. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 131 136
Median (Inter-Quartile Range)
Unit of Measure: days
NA [1] 
(55.0 to NA)
NA [1] 
(NA to NA)
[1]
As neither treatment group had over 50% of subjects experiencing relapse during the 26-week randomized-withdrawal phase, the median time to relapse and inter-quartile range was not calculable.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Randomized-withdrawal Period), SPD489 (Randomized-withdrawal Period)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value based on a log-rank test, stratified by 4-week cessation status (Yes, No). 4-week cessation was defined as a subject having no binge days during the 4 weeks prior to randomization.
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Change From Randomized-Withdrawal Baseline in The Number of Binge­ Eating Days Per Week During The Randomized-withdrawal Period
Hide Description A binge day was defined as days during which at least 1 binge episode occurred. As assessed by clinical interview based on subject binge diary. Binge eating information was captured via a self-report paper diary. The binge diary captured the number of binges per day, total hours per day spent binging, type of binge (at mealtime or at another time other than mealtime), and a description of the binge (amounts and types of foods). Binge frequency was reviewed by the clinician with the subject to confirm reported binge episodes per day. A negative change from Baseline indicates that binge-related behavior decreased. The randomized ­withdrawal-baseline was defined as the weekly average number of binge days for the 14 days prior to the Randomization Visit (Visit 8).
Time Frame Randomized­-withdrawal baseline (Visit 8; 12 weeks after start of open­ label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38])
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 included only participants who completed randomized treatment (placebo: n=50; SPD489: n=102).
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized­-Withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70 mg was continued throughout the 26-week double-blind randomized-­withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 131 136
Least Squares Mean (Standard Error)
Unit of Measure: days
0.63  (0.076) 0.02  (0.061)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Randomized-withdrawal Period), SPD489 (Randomized­-Withdrawal Period)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal P-value not adjusted for multiplicity.
Method mixed­ effects model for repeated measur
Comments MMRM over all post-randomization visits during the randomized-withdrawal phase. Value for change from baseline = outcome variable.
Method of Estimation Estimation Parameter difference in LS mean
Estimated Value -0.61
Confidence Interval (2-Sided) 95%
-0.81 to -0.42
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period
Hide Description The CGI-S permits a global evaluation of a subject’s condition and severity of symptoms. The CGI-S was performed to rate the severity of a subject’s condition based on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill).
Time Frame Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 131 136
Measure Type: Number
Unit of Measure: percentage of participants
Normal, Not at All Ill 45.0 81.6
Borderline Mentally Ill 10.7 11.8
Mildly Ill 14.5 2.2
Moderately Ill 22.1 2.2
Markedly Ill 6.9 2.2
Severely Ill 0.0 0.0
Among the Most Extremely Ill 0.8 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Randomized-withdrawal Period), SPD489 (Randomized-withdrawal Period)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Unadjusted P-value for the difference in distribution between treatment groups in CGI-S.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test with a modified ridit score, adjusting for Visit 8 (Week 12) CGI-S as the covariate.
4.Secondary Outcome
Title Change From Randomized-Withdrawal Baseline in The Total Score of The Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) During The Randomized-withdrawal Period
Hide Description The Y-BOCS-BE measures the obsession of binge eating thoughts and compulsiveness of binge eating behaviors. The scale is a clinician rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms). The scale includes questions regarding the amount of time spent on obsessions, impairment or distress experienced, and resistance and control over these thoughts. The same types of questions were asked about compulsions (ie, time spent, interference, etc.).Total scores range from 0 to 40. A total score of 0-7 is sub-clinical, 8-15 is mild, 16-23 is moderate, 24-31 is severe, and 32-40 is extreme. A decrease from baseline in Y-BOCS-BE Total Score represents an improvement in obsession with binge-eating thoughts or compulsiveness of binge-eating behaviors.
Time Frame Randomized-withdrawal baseline (Visit 8; 12 weeks after start of open-label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38])
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 included only participants who completed randomized treatment (placebo: n=54; SPD489: n=107).
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 131 136
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
5.5  (0.66) -0.0  (0.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Randomized-withdrawal Period), SPD489 (Randomized-withdrawal Period)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal P-value not adjusted for multiplicity.
Method mixed-effects model for repeated measure
Comments MMRM over all post-randomization visits during the randomized-withdrawal phase. Value for change from baseline = outcome variable.
Method of Estimation Estimation Parameter difference in LS mean
Estimated Value -5.6
Confidence Interval (2-Sided) 95%
-7.2 to -3.9
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility at Endpoint of The Open-label Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The Open-label Safety Population (OSP), defined as participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
Arm/Group Title Open-label Safety Population
Hide Arm/Group Description:
The Open-label Safety Population included all participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment.
Overall Number of Participants Analyzed 397
Measure Type: Number
Unit of Measure: percentage of participants
I have no problems in walking about 87.9
I have slight problems in walking about 9.8
Moderate problems in walking about 1.5
I have severe problems in walking about 0.8
I am unable to walk about 0
6.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5­-Dimension 5­-Level Self­-Report Questionnaire (EQ­-5D­-5L) For Mobility at Endpoint of The Randomized-withdrawal Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 116 127
Measure Type: Number
Unit of Measure: percentage of participants
I have no problems in walking about 83.6 91.3
I have slight problems in walking about 14.7 6.3
Moderate problems in walking about 1.7 1.6
I have severe problems in walking about 0.0 0.8
I am unable to walk about 0.0 0.0
7.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Open-label Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
Arm/Group Title Open-label Safety Population
Hide Arm/Group Description:
The Open-label Safety Population included all participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment.
Overall Number of Participants Analyzed 397
Measure Type: Number
Unit of Measure: percentage of participants
I have no problems washing or dressing myself 98.7
I have slight problems washing or dressing myself 0.8
Moderate problems washing or dressing myself 0.3
I have severe problems washing or dressing myself 0.3
I am unable to wash or dress myself 0
8.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS. Three participants in the placebo group were randomized and included in the RSAS but not included in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 116 127
Measure Type: Number
Unit of Measure: percentage of participants
I have no problems washing or dressing myself 98.3 98.4
I have slight problems washing or dressing myself 0.9 0.8
Moderate problems washing or dressing myself 0.9 0.8
I have severe problems washing or dressing myself 0.0 0.0
I am unable to wash or dress myself 0.0 0.0
9.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Open-label Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
Arm/Group Title Open-label Safety Population
Hide Arm/Group Description:
The Open-label Safety Population included all participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment.
Overall Number of Participants Analyzed 397
Measure Type: Number
Unit of Measure: percentage of participants
I have no problems doing my usual activities 88.9
I have slight problems doing my usual activities 8.1
Moderate problems doing my usual activities 2.3
I have severe problems doing my usual activities 0.8
I am unable to do my usual activities 0
10.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 116 127
Measure Type: Number
Unit of Measure: percentage of participants
I have no problems doing my usual activities 79.3 86.6
I have slight problems doing my usual activities 16.4 11.0
Moderate problems doing my usual activities 2.6 0.8
I have severe problems doing my usual activities 0.0 1.6
I am unable to do my usual activities 1.7 0.0
11.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Open-label Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
Arm/Group Title Open-label Safety Population
Hide Arm/Group Description:
The Open-label Safety Population included all participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment.
Overall Number of Participants Analyzed 397
Measure Type: Number
Unit of Measure: percentage of participants
I have no pain or discomfort 72.3
I have slight pain or discomfort 20.9
Moderate pain or discomfort 5.3
I have severe pain or discomfort 1.3
I have extreme pain or discomfort 0.3
12.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS. Three participants in the placebo group were randomized and included in the RSAS but not included in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 116 127
Measure Type: Number
Unit of Measure: percentage of participants
I have no pain or discomfort 75.0 71.7
I have slight pain or discomfort 16.4 18.1
Moderate pain or discomfort 8.6 8.7
I have severe pain or discomfort 0.0 0.0
I have extreme pain or discomfort 0.0 1.6
13.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Open-label Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Hide Outcome Measure Data
Hide Analysis Population Description
The OSP. Not all participants had data collected for this outcome. Visit 8 could include participants who discontinued but completed a safety and efficacy assessment.
Arm/Group Title Open-label Safety Population
Hide Arm/Group Description:
The Open-label Safety Population included all participants who had taken at least 1 dose of SPD489 in the open-label period and who had a post-baseline safety assessment.
Overall Number of Participants Analyzed 397
Measure Type: Number
Unit of Measure: percentage of participants
I am not anxious or depressed 80.9
I am slightly anxious or depressed 15.6
Moderately anxious or depressed 2.3
I am severely anxious or depressed 1.0
I am extremely anxious or depressed 0.3
14.Secondary Outcome
Title Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period
Hide Description The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.
Time Frame Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
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Hide Analysis Population Description
The FAS. Three participants in the placebo group were randomized and included in the RSAS but not in the FAS. Not all participants in the FAS had data collected for this outcome. Visit 21 could include participants who discontinued but completed a final safety and efficacy assessment.
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 116 127
Measure Type: Number
Unit of Measure: percentage of participants
I am not anxious or depressed 66.4 79.5
I am slightly anxious or depressed 26.7 15.7
Moderately anxious or depressed 4.3 3.1
I am severely anxious or depressed 2.6 0.8
I am extremely anxious or depressed 0.0 0.8
15.Secondary Outcome
Title Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Open-label Period
Hide Description The C-SSRS is a semistructured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answer to the first 2 ideation questions was "yes," the clinician asked questions 3-5. Active suicidal ideation included any participant who answered "yes" to questions 2-5. If the answers to ideation questions 1 and 2 were "No," then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide.
Time Frame Visit 8 (12 weeks after start of open-label treatment [Week 12])
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Hide Analysis Population Description
The OSP. Three participants in the OSP did not have data collected for this outcome. Visit 8 included only participants who completed open-label treatment.
Arm/Group Title Open-label Safety Population
Hide Arm/Group Description:
The Open-label Safety Population included all participants who had taken at least 1 dose of SPD489 in the open-label phase and who had a post-baseline safety assessment.
Overall Number of Participants Analyzed 408
Measure Type: Number
Unit of Measure: participants
Suicidal Behavior 0
Active Suicidal Ideation 0
Non-Suicidal Self-Injurious Behavior 2
16.Secondary Outcome
Title Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period
Hide Description The C-SSRS is a semistructured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answer to the first 2 ideation questions was "yes," the clinician asked questions 3-5. Active suicidal ideation included any participant who answered "yes" to questions 2-5. If the answers to ideation questions 1 and 2 were "No," then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide.
Time Frame Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
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Hide Analysis Population Description
The Randomized Safety Analysis Set (RSAS), defined as participants in the SAS who were randomized and took at least 1 dose of investigational product in the randomized-withdrawal period. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS. Three participants had no data for this outcome.
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 131 136
Measure Type: Number
Unit of Measure: participants
Suicidal Behavior 0 0
Active Suicidal Ideation 0 0
Non-Suicidal Self-Injurious Behavior 0 1
17.Secondary Outcome
Title Total Scores For The Amphetamine Cessation Symptom Assessment (ACSA) Scale During Follow-up
Hide Description The ACSA was used in this study to assess potential withdrawal symptoms associated with chronic use of SPD489. The ACSA is a self-completed scale used to assess withdrawal symptoms. The scale has 16 symptom items rated on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The ACSA total score ranges from 0-64, where a higher score indicates greater withdrawal symptom severity.
Time Frame Visit 21 (26 weeks after randomization [Week 38] or Early Termination) and Visit 22 (7 days post last dose)
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Hide Analysis Population Description
The RSAS. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS. Visits 21 and 22 could include participants who discontinued but completed a final safety and efficacy assessment. Not all participants had data for this outcome.
Arm/Group Title Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description:
During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
Overall Number of Participants Analyzed 134 136
Mean (Standard Deviation)
Unit of Measure: units on a scale
Visit 21, n=88, 94 7.6  (8.33) 4.9  (7.81)
Visit 22, n=75, 78 4.6  (5.84) 5.3  (7.98)
Time Frame [Not Specified]
Adverse Event Reporting Description Treatment emergent AEs are reported for the Open-label Safety Population and Randomized Safety Analysis Set (Randomized-withdrawal Period). Seven participants were enrolled but not treated or included in the Open-label Safety Population. Four (placebo) and one (SPD489) participants were randomized but not treated and thus not included in the RSAS.
 
Arm/Group Title SPD489 (Open-label Period) Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Hide Arm/Group Description SPD489 treatment was taken orally once daily at approximately 7:00 AM. All participants began treatment with SPD489 at the lowest dose level (30mg) during the 4-week open-label dose-optimization period. After 1 week of treatment at 30mg, all participants were titrated to the next dose level (50mg). After 1 week of treatment at 50mg, all participants were titrated to the highest dose level (70mg), as tolerated and as clinically indicated. After 1 week of treatment at the highest dose, the participant could have been down-titrated to 50mg; no further dose adjustments were permitted. The optimal daily dose of 50 or 70mg achieved during dose-optimization was maintained throughout the 8-week dose-maintenance period. The total time of the open-label period was 12 weeks. During the 26-week double-blind randomized-withdrawal phase, participants randomized to placebo received matching placebo capsules daily. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week . For participants randomized to SPD489, the optimal daily dose of 50 or 70mg was continued throughout the 26-week double-blind randomized-withdrawal phase. After the 26-week double-blind randomized-withdrawal phase, participants were followed for 1 week.
All-Cause Mortality
SPD489 (Open-label Period) Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
SPD489 (Open-label Period) Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/411 (0.73%)      0/134 (0.00%)      2/136 (1.47%)    
Congenital, familial and genetic disorders       
Congenital Anomaly in Offspring  1  1/411 (0.24%)  1 0/134 (0.00%)  0 0/136 (0.00%)  0
Infections and infestations       
Pneumonia  1  1/411 (0.24%)  1 0/134 (0.00%)  0 0/136 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast Cancer  1  0/411 (0.00%)  0 0/134 (0.00%)  0 1/136 (0.74%)  1
Nervous system disorders       
Convulsion  1  1/411 (0.24%)  1 0/134 (0.00%)  0 0/136 (0.00%)  0
Nerve Root Compression  1  0/411 (0.00%)  0 0/134 (0.00%)  0 1/136 (0.74%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
SPD489 (Open-label Period) Placebo (Randomized-withdrawal Period) SPD489 (Randomized-withdrawal Period)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   303/411 (73.72%)      45/134 (33.58%)      59/136 (43.38%)    
Cardiac disorders       
Tachycardia  1  17/411 (4.14%)  20 0/134 (0.00%)  0 2/136 (1.47%)  3
Palpitations  1  13/411 (3.16%)  13 0/134 (0.00%)  0 1/136 (0.74%)  1
Gastrointestinal disorders       
Dry mouth  1  139/411 (33.82%)  145 2/134 (1.49%)  2 7/136 (5.15%)  7
Nausea  1  35/411 (8.52%)  37 3/134 (2.24%)  3 6/136 (4.41%)  6
Constipation  1  28/411 (6.81%)  29 1/134 (0.75%)  1 4/136 (2.94%)  4
Diarrhoea  1  21/411 (5.11%)  24 3/134 (2.24%)  3 2/136 (1.47%)  2
Abdominal pain upper  1  9/411 (2.19%)  10 1/134 (0.75%)  1 2/136 (1.47%)  2
Dyspepsia  1  3/411 (0.73%)  3 1/134 (0.75%)  1 3/136 (2.21%)  3
General disorders       
Feeling jittery  1  21/411 (5.11%)  26 0/134 (0.00%)  0 0/136 (0.00%)  0
Irritability  1  19/411 (4.62%)  22 4/134 (2.99%)  5 4/136 (2.94%)  4
Fatigue  1  18/411 (4.38%)  19 7/134 (5.22%)  7 4/136 (2.94%)  4
Thirst  1  9/411 (2.19%)  11 0/134 (0.00%)  0 0/136 (0.00%)  0
Infections and infestations       
Nasopharyngitis  1  20/411 (4.87%)  20 9/134 (6.72%)  9 13/136 (9.56%)  15
Upper respiratory tract infection  1  11/411 (2.68%)  11 5/134 (3.73%)  7 11/136 (8.09%)  12
Urinary tract infection  1  7/411 (1.70%)  7 4/134 (2.99%)  4 4/136 (2.94%)  4
Bronchitis  1  5/411 (1.22%)  5 0/134 (0.00%)  0 3/136 (2.21%)  3
Rhinitis  1  0/411 (0.00%)  0 0/134 (0.00%)  0 3/136 (2.21%)  3
Gastroenteritis  1  5/411 (1.22%)  5 3/134 (2.24%)  3 2/136 (1.47%)  2
Investigations       
Blood pressure increased  1  15/411 (3.65%)  17 0/134 (0.00%)  0 1/136 (0.74%)  1
Heart rate increased  1  14/411 (3.41%)  16 0/134 (0.00%)  0 1/136 (0.74%)  1
Weight decreased  1  14/411 (3.41%)  14 1/134 (0.75%)  1 1/136 (0.74%)  1
Weight increased  1  0/411 (0.00%)  0 1/134 (0.75%)  1 3/136 (2.21%)  3
Metabolism and nutrition disorders       
Decreased appetite  1  38/411 (9.25%)  44 0/134 (0.00%)  0 0/136 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Musculoskeletal pain  1  4/411 (0.97%)  5 0/134 (0.00%)  0 4/136 (2.94%)  4
Arthralgia  1  7/411 (1.70%)  8 1/134 (0.75%)  1 3/136 (2.21%)  3
Back pain  1  2/411 (0.49%)  2 0/134 (0.00%)  0 3/136 (2.21%)  3
Nervous system disorders       
Headache  1  66/411 (16.06%)  84 9/134 (6.72%)  9 12/136 (8.82%)  14
Dizziness  1  10/411 (2.43%)  11 0/134 (0.00%)  0 1/136 (0.74%)  4
Somnolence  1  1/411 (0.24%)  1 3/134 (2.24%)  3 5/136 (3.68%)  5
Psychiatric disorders       
Insomnia  1  46/411 (11.19%)  46 2/134 (1.49%)  2 1/136 (0.74%)  1
Anxiety  1  29/411 (7.06%)  32 2/134 (1.49%)  2 2/136 (1.47%)  2
Initial insomnia  1  6/411 (1.46%)  7 2/134 (1.49%)  3 4/136 (2.94%)  4
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain  1  5/411 (1.22%)  6 2/134 (1.49%)  2 3/136 (2.21%)  3
Skin and subcutaneous tissue disorders       
Hyperhidrosis  1  23/411 (5.60%)  24 0/134 (0.00%)  0 3/136 (2.21%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Name/Title: Study Physician
Organization: Shire Development LLC
Phone: +1 866 842 5335
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02009163     History of Changes
Other Study ID Numbers: SPD489-346
2012-004457-88 ( EudraCT Number )
First Submitted: December 6, 2013
First Posted: December 11, 2013
Results First Submitted: January 28, 2016
Results First Posted: April 1, 2016
Last Update Posted: April 1, 2016