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Maintenance of Efficacy of Extended-Release Guanfacine HCl in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01081145
First received: March 3, 2010
Last updated: November 25, 2014
Last verified: May 2014
History of Changes
Results First Received: May 9, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Attention-deficit/Hyperactivity Disorder
Interventions: Drug: Extended-release Guanfacine Hydrochloride
Other: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight
Placebo Administered as a once-daily oral dose

Participant Flow for 2 periods

 Period 1:   Open-Label Phase
    Guanfacine Hydrochloride   Placebo
STARTED   528   0 
COMPLETED   316   0 
NOT COMPLETED   212   0 
Lack of Efficacy                56                0 
Response criteria not met                46                0 
Adverse Event                42                0 
Withdrawal by Subject                41                0 
Not specified                12                0 
Lost to Follow-up                11                0 
Protocol Violation                4                0 

Period 2:   Double-Blind Randomized-Withdrawal Phase
    Guanfacine Hydrochloride   Placebo
STARTED   157   159 
COMPLETED   76   53 
NOT COMPLETED   81   106 
Adverse Event                3                2 
Protocol Violation                1                0 
Withdrawal by Subject                10                8 
Lost to Follow-up                3                2 
Lack of Efficacy                13                20 
Treatment failure criteria met                47                71 
Not specified                4                3 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Open-label Safety Population defined as all subjects who took at least 1 dose of any investigational product during the study. Two subjects did not receive investigational product, therefore n = 526.

Reporting Groups
  Description
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Baseline Measures
   Guanfacine Hydrochloride 
Overall Participants Analyzed 
[Units: Participants]
 		 526 
Age 
[Units: Years]
Mean (Standard Deviation) 		 10.7  (2.7) 
Age, Customized 
[Units: Participants]
 		 
6-12 years   391 
13-17 years   135 
Gender 
[Units: Participants]
 		 
Female   130 
Male   396 
Region of Enrollment 
[Units: Participants]
 		 
BELGIUM   19 
CANADA   30 
FRANCE   14 
GERMANY   27 
ITALY   31 
NETHERLANDS   29 
SPAIN   68 
SWEDEN   5 
UNITED KINGDOM   25 
UNITED STATES   278 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase   [ Time Frame: 26 weeks ]

Measure Type Primary
Measure Title Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase
Measure Description Treatment failure was defined as >= 50% increase (worsening) in ADHD-RS-IV total score and a >= 2 point increase (worsening) in CGI-S score compared with the respective scores at the Double-blind Randomized-withdrawal Baseline Visit at 2 consecutive Double-blind Randomized-withdrawal Phase visits. Subjects meeting these criteria were regarded as treatment failures regardless of whether or not they were withdrawn. All subjects who discontinued the study for any reason were regarded as treatment failures for the primary analysis.
Time Frame 26 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized Full Analysis Set (FAS) defined as all subjects who were randomized and took at least 1 dose of investigational product during the Double-blind Randomized-withdrawal Phase. Subjects from Site 801 were excluded from the Randomized FAS.

Reporting Groups
  Description
Placebo Administered as a once-daily oral dose
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Placebo   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 151   150 
Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase 
[Units: Percentage of treatment failures]
Number (95% Confidence Interval) 		 64.9 
 (57.3 to 72.5)  		 49.3 
 (41.3 to 57.3) 


Statistical Analysis 1 for Percentage of Participants With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Cochran-Mantel-Haenszel
P Value [4] 0.006
Difference in treatment failures [5] -15.6
95% Confidence Interval -26.6 to -4.5
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



2.  Secondary:   Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase   [ Time Frame: 26 weeks ]

Measure Type Secondary
Measure Title Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase
Measure Description Treatment failure was defined as >= 50% increase (worsening) in ADHD-RS-IV total score and a >= 2 point increase (worsening) in CGI-S score compared with the respective scores at the Double-blind Randomized-withdrawal Baseline Visit at 2 consecutive Double-blind Randomized-withdrawal Phase visits. Subjects meeting these criteria were regarded as treatment failures regardless of whether or not they were withdrawn. All subjects who discontinued the study for any reason were regarded as treatment failures for the primary analysis.
Time Frame 26 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized FAS

Reporting Groups
  Description
Placebo Administered as a once-daily oral dose
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Placebo   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 151   150 
Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase 
[Units: Days]
Median (95% Confidence Interval) 		 56.0 
 (44.0 to 97.0)  		 218.0 [1] 
 (118.0 to N/A) 
[1] There were not enough treatment failure events by study completion to calculate an upper CI.


Statistical Analysis 1 for Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.003
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



3.  Secondary:   Change From Double-Blind Randomized-Withdrawal Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - Last Observation Carried Forward (LOCF)   [ Time Frame: Baseline and week 26 ]

Measure Type Secondary
Measure Title Change From Double-Blind Randomized-Withdrawal Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - Last Observation Carried Forward (LOCF)
Measure Description The ADHD-RS-IV 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.
Time Frame Baseline and week 26  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized FAS

Reporting Groups
  Description
Placebo Administered as a once-daily oral dose
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Placebo   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 151   150 
Change From Double-Blind Randomized-Withdrawal Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - Last Observation Carried Forward (LOCF) 
[Units: Units on a scale]
Least Squares Mean (Standard Error) 		 15.89  (1.225)   9.64  (1.21) 


Statistical Analysis 1 for Change From Double-Blind Randomized-Withdrawal Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - Last Observation Carried Forward (LOCF)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] ANCOVA
P Value [4] <0.001
Difference in Least Squares Mean [5] -6.24
95% Confidence Interval -9.01 to -3.48
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Nominal p-value uncorrected for multiplicity.
[5] Other relevant estimation information:
  No text entered.



4.  Secondary:   Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale During the Double-Blind Randomized-Withdrawal Phase - LOCF   [ Time Frame: 26 weeks ]

Measure Type Secondary
Measure Title Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale During the Double-Blind Randomized-Withdrawal Phase - LOCF
Measure Description CGI-S assesses the severity of the subject's condition on a 7-point scale: 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill)
Time Frame 26 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized FAS

Reporting Groups
  Description
Placebo Administered as a once-daily oral dose
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Placebo   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 151   150 
Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale During the Double-Blind Randomized-Withdrawal Phase - LOCF 
[Units: Percentage of subjects]
 		 32.5   50.0 


Statistical Analysis 1 for Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on Clinical Global Impression-Severity of Illness (CGI-S) Scale During the Double-Blind Randomized-Withdrawal Phase - LOCF
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Cochran-Mantel-Haenszel
P Value [4] 0.001
Difference in percent of subjects [5] 17.5
95% Confidence Interval 6.6 to 28.5
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Nominal p-value uncorrected for multiplicity.
[5] Other relevant estimation information:
  No text entered.



5.  Secondary:   Change From Double-Blind Randomized-Withdrawal Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - LOCF   [ Time Frame: Baseline and week 26 ]

Measure Type Secondary
Measure Title Change From Double-Blind Randomized-Withdrawal Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - LOCF
Measure Description The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.
Time Frame Baseline and week 26  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized FAS

Reporting Groups
  Description
Placebo Administered as a once-daily oral dose
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Placebo   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 151   150 
Change From Double-Blind Randomized-Withdrawal Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - LOCF 
[Units: Units on a scale]
Least Squares Mean (Standard Error) 		 0.23  (0.036)   0.16  (0.035) 


Statistical Analysis 1 for Change From Double-Blind Randomized-Withdrawal Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 26 of the Double-Blind Randomized-Withdrawal Phase - LOCF
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] ANCOVA
P Value [4] 0.118
Difference in Least Squares Mean [5] -0.06
95% Confidence Interval -0.14 to 0.02
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Nominal p-value uncorrected for multiplicity.
[5] Other relevant estimation information:
  No text entered.



6.  Secondary:   Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF   [ Time Frame: 26 weeks ]

Measure Type Secondary
Measure Title Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF
Measure Description HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.
Time Frame 26 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized FAS

Reporting Groups
  Description
Placebo Administered as a once-daily oral dose
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Placebo   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 142   138 
Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF 
[Units: Units on a scale]
Mean (Standard Deviation) 		 0.899  (0.1272)   0.900  (0.1229) 

No statistical analysis provided for Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF



7.  Secondary:   Columbia-Suicide Severity Rating Scale During Double-Blind Randomized-Withdrawal Phase   [ Time Frame: 26 weeks ]

Measure Type Secondary
Measure Title Columbia-Suicide Severity Rating Scale During Double-Blind Randomized-Withdrawal Phase
Measure Description C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. 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 assessment is done by the nature of the responses, not by a numbered scale.
Time Frame 26 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized Safety Population defined as all subjects who were randomized and who took at least 1 dose of investigational product during the Double-blind Randomized-withdrawal Phase.

Reporting Groups
  Description
Placebo Administered as a once-daily oral dose
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Placebo   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 158   157 
Columbia-Suicide Severity Rating Scale During Double-Blind Randomized-Withdrawal Phase 
[Units: Participants]
 		   
Suicidal ideation   2   2 
Suicidal behavior   0   0 

No statistical analysis provided for Columbia-Suicide Severity Rating Scale During Double-Blind Randomized-Withdrawal Phase



8.  Secondary:   Change From Open-Label Baseline in ADHD-RS-IV Total Score at Week 13 of the Open-Label Phase - LOCF   [ Time Frame: Baseline and 13 weeks ]

Measure Type Secondary
Measure Title Change From Open-Label Baseline in ADHD-RS-IV Total Score at Week 13 of the Open-Label Phase - LOCF
Measure Description The ADHD-RS-IV 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.
Time Frame Baseline and 13 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Open-label Full Analysis Set (FAS) defined as all subjects who took at least 1 dose of any investigational product during the study. The Subjects from Site 801 were excluded from the Open-label FAS.

Reporting Groups
  Description
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 497 
Change From Open-Label Baseline in ADHD-RS-IV Total Score at Week 13 of the Open-Label Phase - LOCF 
[Units: Units on a scale]
Mean (Standard Deviation) 		 -25.2  (11.97) 


Statistical Analysis 1 for Change From Open-Label Baseline in ADHD-RS-IV Total Score at Week 13 of the Open-Label Phase - LOCF
Groups [1] Guanfacine Hydrochloride
Statistical Test Type [2] Superiority or Other
Statistical Method [3] t-test, 2 sided
P Value [4] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Nominal p-value uncorrected for multiplicity.



9.  Secondary:   Percentage of Responders in the Open-Label Phase - LOCF   [ Time Frame: 13 weeks ]

Measure Type Secondary
Measure Title Percentage of Responders in the Open-Label Phase - LOCF
Measure Description Response is defined as a percentage decrease (improvement) from Baseline in the ADHD-RS-IV total score of >=30% and a CGI-S score of 1 or 2.
Time Frame 13 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Open-label FAS

Reporting Groups
  Description
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 497 
Percentage of Responders in the Open-Label Phase - LOCF 
[Units: Percentage of participants]
 		 68.6 

No statistical analysis provided for Percentage of Responders in the Open-Label Phase - LOCF



10.  Secondary:   Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores During Open-Label Phase - LOCF   [ Time Frame: 13 weeks ]

Measure Type Secondary
Measure Title Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores During Open-Label Phase - LOCF
Measure 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 13 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Open-label FAS

Reporting Groups
  Description
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 497 
Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores During Open-Label Phase - LOCF 
[Units: Percentage of participants]
 		 76.1 

No statistical analysis provided for Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores During Open-Label Phase - LOCF



11.  Secondary:   Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on CGI-S Scale During the Open-Label Phase - LOCF   [ Time Frame: 13 weeks ]

Measure Type Secondary
Measure Title Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on CGI-S Scale During the Open-Label Phase - LOCF
Measure Description CGI-S assesses the severity of the subject's condition on a 7-point scale: 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill)
Time Frame 13 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Open-label FAS

Reporting Groups
  Description
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 503 
Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on CGI-S Scale During the Open-Label Phase - LOCF 
[Units: Percentage of participants]
 		 68.9 

No statistical analysis provided for Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on CGI-S Scale During the Open-Label Phase - LOCF



12.  Secondary:   Change From Open-Label Baseline in WFIRS-P Global Score at Week 13 of the Open-Label Phase - LOCF   [ Time Frame: Baseline and week 13 ]

Measure Type Secondary
Measure Title Change From Open-Label Baseline in WFIRS-P Global Score at Week 13 of the Open-Label Phase - LOCF
Measure Description The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.
Time Frame Baseline and week 13  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Open-label FAS

Reporting Groups
  Description
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 405 
Change From Open-Label Baseline in WFIRS-P Global Score at Week 13 of the Open-Label Phase - LOCF 
[Units: Units on a scale]
Mean (Standard Deviation) 		 -0.35  (0.414) 


Statistical Analysis 1 for Change From Open-Label Baseline in WFIRS-P Global Score at Week 13 of the Open-Label Phase - LOCF
Groups [1] Guanfacine Hydrochloride
Statistical Test Type [2] Superiority or Other
Statistical Method [3] t-test, 2 sided
P Value [4] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Nominal p-value uncorrected for multiplicity.



13.  Secondary:   HUI 2/3 Scores During the Open-Label Phase - LOCF   [ Time Frame: 13 weeks ]

Measure Type Secondary
Measure Title HUI 2/3 Scores During the Open-Label Phase - LOCF
Measure Description HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.
Time Frame 13 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Open-label FAS

Reporting Groups
  Description
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 417 
HUI 2/3 Scores During the Open-Label Phase - LOCF 
[Units: Units on a scale]
Mean (Standard Deviation) 		 0.892  (0.1230) 

No statistical analysis provided for HUI 2/3 Scores During the Open-Label Phase - LOCF



14.  Secondary:   Columbia-Suicide Severity Rating Scale During Open-Label Phase   [ Time Frame: 13 weeks ]

Measure Type Secondary
Measure Title Columbia-Suicide Severity Rating Scale During Open-Label Phase
Measure Description C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. 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 assessment is done by the nature of the responses, not by a numbered scale.
Time Frame 13 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Open-label Safety Population defined as all subjects who took at least 1 dose of any investigational product during the study.

Reporting Groups
  Description
Guanfacine Hydrochloride Administered as a once-daily oral dose between 1-7mg/day depending on age and weight

Measured Values
   Guanfacine Hydrochloride 
Participants Analyzed 
[Units: Participants]
 		 526 
Columbia-Suicide Severity Rating Scale During Open-Label Phase 
[Units: Participants]
 		 
Suicidal ideation   1 
Suicidal behavior   2 

No statistical analysis provided for Columbia-Suicide Severity Rating Scale During Open-Label Phase




  Serious Adverse Events
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  Other Adverse Events
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  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01081145     History of Changes
Other Study ID Numbers: SPD503-315
2009-018161-12 ( EudraCT Number )
Study First Received: March 3, 2010
Results First Received: May 9, 2014
Last Updated: November 25, 2014