Clinical Trial Results:
A Phase 3, Double-Blind, Placebo-Controlled, Multicentre, Randomised-Withdrawal, Long-Term Maintenance of Efficacy and Safety Study of Extended-Release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 with Attention-deficit/Hyperactivity Disorder
Summary
|
|
EudraCT number |
2009-018161-12 |
Trial protocol |
GB DE NL ES SE BE IT |
Global end of trial date |
09 Jul 2013
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
04 Sep 2018
|
First version publication date |
07 Dec 2014
|
Other versions |
v1 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
SPD503-315
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01081145 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Shire Development LLC
|
||
Sponsor organisation address |
725 Chesterbrook Boulevard, Wayne, United States, 19087
|
||
Public contact |
Study Physician, Shire Development LLC, 1 866 842 5335 ,
|
||
Scientific contact |
Study Physician, Shire Development LLC, 1 866 842 5335 ,
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000745-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
11 Feb 2014
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
09 Jul 2013
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The primary objective of this study is to evaluate the long-term maintenance of efficacy of SPD503 in children and adolescents (6-17 years) with attention-deficit/hyperactivity disorder (ADHD) who respond to an initial open label, short-term treatment with SPD503.
|
||
Protection of trial subjects |
The role of the DMC was to protect the interests of subjects in the study and of potential subjects, by review of accumulating safety and tolerability data as it was generated. This study was conducted in accordance with International Conference on Harmonisation of good clinical practice (GCP), the principles of the Declaration of Helsinki, as well as other applicable local ethical and legal requirements.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 May 2010
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Netherlands: 29
|
||
Country: Number of subjects enrolled |
Spain: 68
|
||
Country: Number of subjects enrolled |
Sweden: 5
|
||
Country: Number of subjects enrolled |
United Kingdom: 25
|
||
Country: Number of subjects enrolled |
Belgium: 19
|
||
Country: Number of subjects enrolled |
France: 14
|
||
Country: Number of subjects enrolled |
Germany: 27
|
||
Country: Number of subjects enrolled |
Italy: 31
|
||
Country: Number of subjects enrolled |
Canada: 30
|
||
Country: Number of subjects enrolled |
United States: 280
|
||
Worldwide total number of subjects |
528
|
||
EEA total number of subjects |
218
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
334
|
||
Adolescents (12-17 years) |
194
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
||||||||||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||||||||||
Recruitment details |
Participants took part in the study at 67 investigative sites in Belgium, Canada, France, Italy, Germany, the Netherlands, Spain, Sweden, the United Kingdom, and the United States from 11 May 2010 to 9 July 2013. | |||||||||||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||||||||||
Screening details |
Children and adolescents aged 6-17 with attention-deficit/hyperactivity disorder were enrolled in 1 of 2 [guanfacine hydrochloride 1-7 mg once daily (QD); placebo QD] treatment groups. | |||||||||||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||||||||||
Period 1 title |
Open-Label Phase
|
|||||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||||||||
Arm title
|
Guanfacine Hydrochloride | |||||||||||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Guanfacine Hydrochloride
|
|||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||
Dosage and administration details |
Administered as a once-daily oral dose between 1-7mg/day depending on age and weight
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Period 2
|
||||||||||||||||||||||||||||||||||
Period 2 title |
Double-Blind Randomized-Withdrawal Phase
|
|||||||||||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||||||||
Blinding implementation details |
The actual treatment given to individual subjects during the Double-Blind
Randomized-Withdrawal Phase was determined by a randomization schedule. The associated
treatment assignments giving details of individual subject treatment were automatically
assigned by the interactive response technology (IRT).
|
|||||||||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||||||||
Arm title
|
Guanfacine Hydrochloride | |||||||||||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Guanfacine Hydrochloride
|
|||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||
Dosage and administration details |
Administered as a once-daily oral dose between 1-7mg/day depending on age and weight
|
|||||||||||||||||||||||||||||||||
Arm title
|
Placebo | |||||||||||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||
Dosage and administration details |
Administered as a once-daily oral dose
|
|||||||||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Open-Label Phase
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Guanfacine Hydrochloride
|
||
Reporting group description |
- | ||
Reporting group title |
Guanfacine Hydrochloride
|
||
Reporting group description |
- | ||
Reporting group title |
Placebo
|
||
Reporting group description |
- |
|
|||||||||||||
End point title |
Percentage of Subjects With Treatment Failures During the Double-Blind Randomized-Withdrawal Phase | ||||||||||||
End point 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.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
26 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment Failures | ||||||||||||
Comparison groups |
Guanfacine Hydrochloride v Placebo
|
||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.006 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Difference in Treatment Failures | ||||||||||||
Point estimate |
-15.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-26.6 | ||||||||||||
upper limit |
-4.5 |
|
||||||||||
End point title |
Time to Treatment Failure During the Double-Blind Randomized-Withdrawal Phase | |||||||||
End point 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.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
26 weeks
|
|||||||||
|
||||||||||
Statistical analysis title |
Time to Treatment Failure | |||||||||
Comparison groups |
Placebo v Guanfacine Hydrochloride
|
|||||||||
Number of subjects included in analysis |
301
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.003 | |||||||||
Method |
Logrank | |||||||||
Confidence interval |
|
|||||||||||||
End point 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) | ||||||||||||
End point 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 26
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Change From Baseline in ADHD-RS-IV Score Week 26 | ||||||||||||
Comparison groups |
Guanfacine Hydrochloride v Placebo
|
||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [1] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Difference in Least Squares Mean | ||||||||||||
Point estimate |
-6.24
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-9.01 | ||||||||||||
upper limit |
-3.48 | ||||||||||||
Notes [1] - Nominal p-value uncorrected for multiplicity. |
|
|||||||||||||
End point title |
Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on the Clinical Global Impression-Severity of Illness (CGI-S) Scale During the Double-Blind Randomized-Withdrawal Phase - LOCF | ||||||||||||
End point 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)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
26 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Clinical Global Impressions - Severity | ||||||||||||
Comparison groups |
Guanfacine Hydrochloride v Placebo
|
||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.001 [2] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Difference in Percent of Subjects | ||||||||||||
Point estimate |
17.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
6.6 | ||||||||||||
upper limit |
28.5 | ||||||||||||
Notes [2] - Nominal p-value uncorrected for multiplicity. |
|
|||||||||||||
End point 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 | ||||||||||||
End point 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 26
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Change from Baseline WFIRS-P Global Score Week 26 | ||||||||||||
Comparison groups |
Guanfacine Hydrochloride v Placebo
|
||||||||||||
Number of subjects included in analysis |
301
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.118 [3] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Difference in Least Squares Mean | ||||||||||||
Point estimate |
-0.06
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.14 | ||||||||||||
upper limit |
0.02 | ||||||||||||
Notes [3] - Nominal p-value uncorrected for multiplicity. |
|
|||||||||||||
End point title |
Health Utilities Index-2/3 (HUI 2/3) Scores During the Double-Blind Randomized-Withdrawal Phase - LOCF | ||||||||||||
End point 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
26 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Columbia-Suicide Severity Rating Scale During the Double-Blind Randomized-Withdrawal Phase | |||||||||||||||
End point 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.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
26 weeks
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change From Open-Label Baseline in ADHD-RS-IV Total Score at Week 13 of the Open-Label Phase - LOCF | ||||||||
End point 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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline and 13 weeks
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percentage of Responders in the Open-Label Phase - LOCF | ||||||||
End point 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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
13 Weeks
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percent of Subjects With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores During the Open-Label Phase - LOCF | ||||||||
End point 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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
13 Weeks
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Percent of Subjects With an Assessment of Normal/Borderline Mentally Ill on the CGI-S Scale During the Open-Label Phase - LOCF | ||||||||
End point 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).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
13 Weeks
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Change From Open-Label Baseline in the WFIRS-P Global Score at Week 13 of the Open-Label Phase - LOCF | ||||||||
End point 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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline and week 13
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
HUI 2/3 Scores During the Open-Label Phase - LOCF | ||||||||
End point 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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
13 weeks
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Columbia-Suicide Severity Rating Scale During the Open-Label Phase | ||||||||||
End point 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.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
13 weeks
|
||||||||||
|
|||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
42 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Guanfacine Hydrochloride (Open-Label Phase)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (Randomized-Withdrawal Phase)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Guanfacine Hydrochloride (Randomized-Withdrawal Phase)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
23 Feb 2010 |
*The maximum dose allowed was reduced from 8mg to 7mg. Text
relating to dose titration in certain adolescent weight groups was updated
to remove the 2mg starting dose and to reflect the reduced maximum
dose.
*Inclusion Criterion #10 was added to exclude subjects with a supine and
standing blood pressure measurement within the 95th percentile for age,
gender, and height.
*Instructions to assess the suitability of subjects to remain in the study
were added. |
||
17 Jun 2010 |
*Inclusion Criterion #3 was updated to allow for inclusion of inattentive
subtype of ADHD.
*Exclusion Criterion #5 wording was updated for clarification that only
clinically significant electrocardiograms were exclusionary.
*Exclusion Criterion #15 wording was changed to specifically exclude
past or present active suicidal ideation and to clarify that intermittent
passive suicidal ideation was not necessarily exclusionary.
*Exclusion Criterion #17 wording was updated to exclude those with a
presence of a serious tic disorder.
*Exclusion Criterion #18 was added to exclude subjects if another
member of the same household was currently participating in the study.
*Body mass index was deleted from Visits 13 and 23.
*Follow-up contact was changed to follow-up visit.
*Added that the subject’s lifetime non-pharmacological interventions
(behavioral therapy) for ADHD were to be collected.
*Added that a subject could have continued participation in behavioral
therapy, provided they had been receiving the therapy for at least
1 month at the time of Enrollment/Visit 2/Week 0 and that the behavioral
therapy must have remained stable throughout the study.
*The fasting requirement was removed for biochemistry samples and it
was clarified that samples could have been drawn with the subject in a
fasting or non-fasting state.
*The Prior Psychoactive Medication Questionnaire and the Oppositional
subscale of the CPRS-R:L were added and study assessments and
statistical methods sections were updated accordingly. |
||
01 Mar 2011 |
Following responses from the Ethics Committees in Spain, Germany, and
The Netherlands, Exclusion Criterion #2 was added to exclude subjects who
were well-controlled on their current ADHD medication with acceptable
tolerability and the parent/caregiver did not object to the current ADHD
medication. |
||
27 Nov 2012 |
*Time to treatment failure was added as a key secondary endpoint.
Statistical methods sections were updated accordingly. Time to
treatment failure is the key secondary objective as defined in the final
SAP (Version 3.0 dated 23 May 2013).
*“Temperature” or “oral temperature” was changed to “temperature (oral
or tympanic)” to clarify that a subject’s temperature could have been
obtained via oral or tympanic readings.
*The sentence “Medical history will be summarized by treatment group
using the number of observations and percentages of subjects reporting
each category” was deleted, as medical history was not being coded. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |