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Safety and Efficacy of SPD489 on Executive Function Behaviors in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01101022
Recruitment Status : Completed
First Posted : April 9, 2010
Results First Posted : February 13, 2012
Last Update Posted : February 6, 2014
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 ADHD Specifically With Executive Function Impairment
Interventions Drug: SPD489
Other: Placebo
Enrollment 161
Recruitment Details  
Pre-assignment Details 161 subjects were enrolled and randomized, but 2 never received any investigational product, and therefore were not included in subject disposition going forward (n = 159).
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose). Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Period Title: Overall Study
Started 79 80
Completed 62 53
Not Completed 17 27
Reason Not Completed
Adverse Event             6             2
Protocol Violation             4             3
Withdrawal by Subject             3             8
Lost to Follow-up             1             4
Lack of Efficacy             0             7
Sponsor decision             1             1
Non-compliance             1             0
Work schedule             1             1
Vacation             0             1
Arm/Group Title SPD489 Placebo Total
Hide Arm/Group Description Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose). Dosed orally once a day at approximately 7:00 AM for 10 weeks. Total of all reporting groups
Overall Number of Baseline Participants 79 80 159
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 80 participants 159 participants
34.2  (10.58) 34.9  (11.02) 34.6  (10.77)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 80 participants 159 participants
<18 years 0 0 0
18 to 55 years 79 80 159
>55 years 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 80 participants 159 participants
Female
39
  49.4%
37
  46.3%
76
  47.8%
Male
40
  50.6%
43
  53.8%
83
  52.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 79 participants 80 participants 159 participants
79 80 159
1.Primary Outcome
Title Change From Baseline in Subject-reported Behavior Rating Inventory of Executive Function - Adult Version Global Executive Composite T-score (BRIEF-A GEC T) at up to 10 Weeks
Hide Description BRIEF-A Global Executive Composite assesses behavioral aspects of executive function. Items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline and up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) defined as all subjects who took 1 dose of investigational product in the double-blind evaluation phase and had 1 primary efficacy assessment.
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Least Squares Mean (Standard Error)
Unit of Measure: T-scores
-22.3  (1.67) -11.1  (1.72)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -11.2
Confidence Interval (2-Sided) 95%
-15.9 to -6.4
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Adult ADHD Impact Module (AIM-A) Multi-Item Scales Total Score at up to 10 Weeks
Hide Description The AIM-A was developed to assess impact of core ADHD symptoms on daily functioning and quality of life. For multi-item scales, subjects respond to items using a Likert scale with responses ranging from 1 (strongly agree) to 5 (strongly disagree). Scores were computed by deriving the mean of the item sets and transforming the scale score on a continuum from 0 to 100 using a standard formula. Higher scores indicate a better quality of life.
Time Frame Baseline and up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Performance and Daily Functioning 38.8  (2.84) 17.2  (2.91)
Impact of symptoms: Daily Interference 30.6  (2.52) 15.7  (2.58)
Impact of symptoms: Bother/Concern 29.3  (2.53) 15.8  (2.60)
Relationships/Communication 21.2  (2.49) 13.4  (2.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Performance and Daily Functioning
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 21.6
Confidence Interval (2-Sided) 95%
13.5 to 29.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Daily Interference
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.9
Confidence Interval (2-Sided) 95%
7.8 to 22.0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Bother/Concern
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 13.5
Confidence Interval (2-Sided) 95%
6.3 to 20.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Relationships/Communication
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0302
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.8
Confidence Interval (2-Sided) 95%
0.8 to 14.9
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Informant-reported BRIEF-A T-scores at up to 10 Weeks
Hide Description BRIEF-A is a validated 75-item questionnaire composed of three indexes (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline and up to10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 71 71
Least Squares Mean (Standard Error)
Unit of Measure: T-scores
Global Executive Composite -10.2  (1.06) -5.3  (1.06)
Behavioral Regulation Index -8.6  (1.04) -5.5  (1.04)
Metacognition Index -10.3  (1.07) -4.6  (1.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Global Executive Composite
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.9
Confidence Interval (2-Sided) 95%
-7.8 to -1.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Behavioral Regulation Index
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0355
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.1
Confidence Interval (2-Sided) 95%
-6.0 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Metacognition Index
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.7
Confidence Interval (2-Sided) 95%
-8.7 to -2.7
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Subject-reported BRIEF-A T-scores at up to 10 Weeks
Hide Description BRIEF-A is a validated 75-item questionnaire composed of three indexes (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Global Executive Composite was reported as the Primary Outcome. Items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline and up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Mean (Standard Error)
Unit of Measure: T-scores
Behavioral Regulation Index -17.5  (1.54) -9.2  (1.58)
Metacognition Index -22.8  (1.63) -11.2  (1.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Behavioral Regulation Index
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.4
Confidence Interval (2-Sided) 95%
-12.7 to -4.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Metacognition Index
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -11.6
Confidence Interval (2-Sided) 95%
-16.3 to -7.0
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Subject-reported BRIEF-A Clinical Subscales T-scores at up to 10 Weeks
Hide Description BRIEF-A clinical subscales items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline and up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Least Squares Mean (Standard Error)
Unit of Measure: T-scores
Inhibit -17.8  (1.50) -9.5  (1.54)
Shift -14.5  (1.46) -7.8  (1.50)
Emotional control -10.9  (1.28) -5.7  (1.31)
Self-monitor -16.6  (1.44) -8.4  (1.48)
Initiate -17.9  (1.38) -8.6  (1.41)
Working memory -23.2  (1.67) -11.9  (1.71)
Plan/Organize -20.8  (1.58) -9.9  (1.62)
Task monitor -20.1  (1.64) -10.8  (1.68)
Organization of materials -16.5  (1.26) -7.6  (1.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Inhibit
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.3
Confidence Interval (2-Sided) 95%
-12.6 to -4.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Shift
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.7
Confidence Interval (2-Sided) 95%
-10.8 to -2.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Emotional control
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0056
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.2
Confidence Interval (2-Sided) 95%
-8.8 to -1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Sef-monitor
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.2
Confidence Interval (2-Sided) 95%
-12.3 to -4.1
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Initiate
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.3
Confidence Interval (2-Sided) 95%
-13.2 to -5.4
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Working memory
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -11.3
Confidence Interval (2-Sided) 95%
-16.0 to -6.6
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Plan/Organize
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.9
Confidence Interval (2-Sided) 95%
-15.4 to -6.4
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Task monitor
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.3
Confidence Interval (2-Sided) 95%
-14.0 to -4.7
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Organization of materials
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.9
Confidence Interval (2-Sided) 95%
-12.5 to -5.3
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Informant-reported BRIEF-A Clinical Subscales T-scores at up to 10 Weeks
Hide Description BRIEF-A clinical subscales items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline and up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 71 71
Least Squares Mean (Standard Error)
Unit of Measure: T-scores
Inhibit -10.2  (1.08) -5.8  (1.08)
Shift -9.1  (1.17) -4.3  (1.17)
Emotional control -5.9  (0.99) -4.6  (0.99)
Self-monitor -6.8  (1.04) -4.6  (1.04)
Initiate -8.6  (1.00) -3.2  (1.00)
Working memory -12.0  (1.22) -5.7  (1.22)
Plan/Organize -9.9  (1.07) -5.0  (1.07)
Task monitor -9.7  (1.21) -3.4  (1.21)
Organization of materials -6.2  (0.97) -3.0  (0.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Inhibit
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0048
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.4
Confidence Interval (2-Sided) 95%
-7.4 to -1.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Shift
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0045
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-8.0 to -1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Emotional control
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3605
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-4.0 to 1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Self-monitor
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1468
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-5.1 to 0.8
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Initiate
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.5
Confidence Interval (2-Sided) 95%
-8.3 to -2.7
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Working memory
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.3
Confidence Interval (2-Sided) 95%
-9.8 to -2.9
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Plan/Organize
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.9
Confidence Interval (2-Sided) 95%
-7.9 to -1.9
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Task monitor
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.3
Confidence Interval (2-Sided) 95%
-9.7 to -2.9
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Organization of materials
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0234
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-5.9 to -0.4
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) With Adult Prompts Total Score at up to 10 Weeks
Hide Description The ADHD-RS consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. Lower scores indicate reduction in symptoms.
Time Frame Baseline and up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-21.4  (1.35) -10.3  (1.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -11.1
Confidence Interval (2-Sided) 95%
-14.9 to -7.3
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Baseline
Hide Description CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Measure Type: Number
Unit of Measure: Percent of participants
Normal, not at all ill 0 0
Borderline mentally ill 0 0
Mildly ill 0 0
Moderately ill 48.1 42.7
Markedly ill 38.0 49.3
Severely ill 13.9 8.0
Among the most extremely ill 0 0
9.Secondary Outcome
Title Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at up to 10 Weeks
Hide Description CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time Frame Up to 10 weeks post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Measure Type: Number
Unit of Measure: Percent of participants
Normal, not at all ill 13.9 6.7
Borderline mentally ill 38.0 16.0
Mildly ill 21.5 10.7
Moderately ill 15.2 37.3
Markedly ill 8.9 25.3
Severely ill 2.5 4.0
Among the most extremely ill 0 0
10.Secondary Outcome
Title Percent of Participants With Improvement on Clinical Global Impression - Global Improvement (CGI-I) at up to 10 Weeks
Hide Description Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Time Frame Up to 10 weeks post-dose
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FAS
Arm/Group Title SPD489 Placebo
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Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Measure Type: Number
Unit of Measure: Percent of participants
78.5 34.7
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Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in AIM-A Multi-Item Scales of Living With ADHD and General Well-being Score at up to 10 Weeks
Hide Description The AIM-A was developed to assess impact of core ADHD symptoms on daily functioning and quality of life. For multi-item scales, subjects respond to items using a Likert scale with responses ranging from 1 (strongly agree) to 5 (strongly disagree). Scores were computed by deriving the mean of the item sets and transforming the scale score on a continuum from 0 to 100 using a standard formula. Higher scores indicate a better quality of life.
Time Frame Baseline and up to 10 weeks
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FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Living with ADHD 14.0  (1.30) 4.9  (1.33)
General Well-being 19.7  (1.69) 9.0  (1.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Living with ADHD
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.1
Confidence Interval (2-Sided) 95%
5.4 to 12.7
Estimation Comments [Not Specified]
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Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments General Well-being
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.8
Confidence Interval (2-Sided) 95%
6.0 to 15.5
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in AIM-A Quality of Life Questions 1 and 4 Scores at up to 10 Weeks
Hide Description

Question 1: 'On a scale of 1 to 10, how would you rate the overall quality of life right now?' It is rated on a scale of 1 (worst) to 10 (best). Higher scores representing a more positive rating.

Question 4: 'How much do you agree with this statement: Over the past few weeks, I've had more good days than bad days?' This is rated on a scale of 1 (strongly agree) to 5 (strongly disagree). Lower scores represent better quality of life.

Time Frame Baseline and up to 10 weeks
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FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 79 75
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Question 1 1.6  (0.16) 1.0  (0.16)
Question 4 -1.0  (0.11) -0.4  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Question 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0184
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
0.1 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Question 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-0.9 to -0.3
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Conner's Adult ADHD Rating Scale-Observer: Short Version (CAARS-O:S) ADHD Index T-score at up to 10 Weeks
Hide Description The CAARS-O:S is an assessment tool with prompts provided to an observer who describes ADHD-related symptoms in an adult subject. The 26-item scale is scored on a 4-point scale from 0 (not at all) to 3 (very much, very frequently). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline and up to 10 weeks
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FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 71 71
Least Squares Mean (Standard Error)
Unit of Measure: T-scores
-11.3  (1.24) -5.8  (1.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.5
Confidence Interval (2-Sided) 95%
-9.0 to -2.1
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in CAARS-O:S Factor-derived Subscale T-scores at up to 10 Weeks
Hide Description The CAARS-O:S is an assessment tool with prompts provided to an observer who describes ADHD-related symptoms in an adult subject. The 26-item scale is scored on a 4-point scale from 0 (not at all) to 3 (very much, very frequently). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline and up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 71 71
Least Squares Mean (Standard Error)
Unit of Measure: T-scores
Inattention/Memory Problems -10.0  (1.12) -4.9  (1.12)
Hyperactivity/Restlessness -9.1  (1.20) -5.0  (1.20)
Impulsivity/Emotional Liability -8.0  (1.01) -4.0  (1.01)
Problems with Self-concept -7.7  (1.10) -3.3  (1.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Inattention/Memory Problems
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.1
Confidence Interval (2-Sided) 95%
-8.2 to -1.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Hyperactivity/Restlessness
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0174
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-7.5 to -0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Impulsivity/Emotional Liability
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0063
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.0
Confidence Interval (2-Sided) 95%
-6.8 to -1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Problems with Self-concept
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0059
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.4
Confidence Interval (2-Sided) 95%
-7.5 to -1.3
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Adult ADHD Quality of Life (AAQoL) Scale Total Score at up to 10 Weeks
Hide Description AAQoL is a validated 29-item scale consisting of 4 subscales. The AAQoL yields a total score and 4 subscale scores. Subjects rate each item on a 5-point Likert scale ranging from 1 (not at all/never) to 5 (extremely/very often). These scores are then transformed to a 0-100 point scale with higher scores indicating better quality of life.
Time Frame Baseline and up to 10 weeks
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FAS
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description:
Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose).
Dosed orally once a day at approximately 7:00 AM for 10 weeks.
Overall Number of Participants Analyzed 28 26
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Life Productivity 38.0  (4.34) 17.0  (4.51)
Psychological Health 19.3  (3.61) 7.2  (3.74)
Life Outlook 18.5  (2.85) 6.0  (2.96)
Relationships 17.1  (3.69) 9.8  (3.83)
Total Score 25.9  (3.04) 11.1  (3.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Life Productivity
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 21.0
Confidence Interval (2-Sided) 95%
8.4 to 33.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Psychological Health
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0242
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 12.1
Confidence Interval (2-Sided) 95%
1.6 to 22.5
Estimation Comments [Not Specified]
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Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Life Outlook
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0038
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 12.5
Confidence Interval (2-Sided) 95%
4.2 to 20.8
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Relationships
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1752
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
-3.4 to 18.0
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection SPD489, Placebo
Comments Total Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.7
Confidence Interval (2-Sided) 95%
5.9 to 23.6
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description Safety Population defined as all subjects who took at least 1 dose of investigational product in the double-blind evaluation phase.
 
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description Dosed orally once a day at approximately 7:00 AM at either 30, 50 or 70 mg for 10 weeks (a 4-week dose optimization period followed by a 6-week dose maintenance period at an optimal dose). Dosed orally once a day at approximately 7:00 AM for 10 weeks.
All-Cause Mortality
SPD489 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
SPD489 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/79 (0.00%)   0/80 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SPD489 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   62/79 (78.48%)   41/80 (51.25%) 
Gastrointestinal disorders     
Diarrhea  6/79 (7.59%)  2/80 (2.50%) 
Dry Mouth  25/79 (31.65%)  6/80 (7.50%) 
Nausea  2/79 (2.53%)  5/80 (6.25%) 
General disorders     
Fatigue  6/79 (7.59%)  3/80 (3.75%) 
Feeling Jittery  10/79 (12.66%)  0/80 (0.00%) 
Irritability  8/79 (10.13%)  3/80 (3.75%) 
Infections and infestations     
Nasopharyngitis  4/79 (5.06%)  4/80 (5.00%) 
Upper Respiratory Tract Infection  5/79 (6.33%)  1/80 (1.25%) 
Investigations     
Heart Rate Increased  4/79 (5.06%)  2/80 (2.50%) 
Weight Decreased  8/79 (10.13%)  0/80 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  4/79 (5.06%)  0/80 (0.00%) 
Decreased Apetite  26/79 (32.91%)  5/80 (6.25%) 
Nervous system disorders     
Headache  20/79 (25.32%)  2/80 (2.50%) 
Psychiatric disorders     
Initial Insomnia  8/79 (10.13%)  5/80 (6.25%) 
Insomnia  10/79 (12.66%)  3/80 (3.75%) 
Libido Decreased  4/79 (5.06%)  0/80 (0.00%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis  5/79 (6.33%)  0/80 (0.00%) 
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
Layout table for Results Point of Contact information
Name/Title: Study Physician
Organization: Shire Pharmaceutical
Phone: 1 866-842-5335
Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01101022     History of Changes
Other Study ID Numbers: SPD489-403
First Submitted: April 7, 2010
First Posted: April 9, 2010
Results First Submitted: September 6, 2011
Results First Posted: February 13, 2012
Last Update Posted: February 6, 2014