Trial Outcomes & Findings for Access to Extended Release Guanfacine HCl for Subjects Who Participated in Studies SPD503-315 or SPD503-316 in Europe (NCT NCT01500694)

Last Updated: 2021-06-16

Results Overview

Systolic Blood pressure was measured at supine and standing position and mean supine systolic blood pressure was reported here. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication \[Visit 19/Early Termination (ET)/Day 714\].

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

215 participants

Primary outcome timeframe

Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Results posted on

2021-06-16

Participant Flow

The study was conducted at 52 sites in 11 countries in Europe: Austria, Belgium, France, Germany, Italy, The Netherlands, Poland, Romania, Spain, Ukraine, and United Kingdom.

Overall 218 participants screened, of them 215 were enrolled and 214 were treated in the study.The first participant's consent was obtained on 20 March 2012 and last participant assessment took place on 15 September 2015.

Participant milestones

Participant milestones
Measure	SPD503 (6-12 Years) Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 milligram \[mg\] or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Overall Study STARTED	131	83
Overall Study COMPLETED	79	54
Overall Study NOT COMPLETED	52	29

Reasons for withdrawal

Reasons for withdrawal
Measure	SPD503 (6-12 Years) Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 milligram \[mg\] or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Overall Study Adverse Event	4	3
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	23	14
Overall Study Lost to Follow-up	2	3
Overall Study Lack of Efficacy	14	5
Overall Study Other	9	3

Baseline Characteristics

Access to Extended Release Guanfacine HCl for Subjects Who Participated in Studies SPD503-315 or SPD503-316 in Europe

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SPD503 (6-12 Years) n=131 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	Total n=214 Participants Total of all reporting groups
Age, Continuous	9.8 years STANDARD_DEVIATION 1.56 • n=5 Participants	14.7 years STANDARD_DEVIATION 1.49 • n=7 Participants	11.7 years STANDARD_DEVIATION 2.82 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	30 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	105 Participants n=5 Participants	53 Participants n=7 Participants	158 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Population: Safety Analysis Set includes all enrolled participants who took at least 1 dose of SPD503. Here, n = number of participants analysed for the specific categories for each arm respectively.

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=131 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Change From Baseline in Mean Systolic Blood Pressure at Final Assessment Baseline (n = 131, 83)	107.5 millimeter of mercury (mmHg) Standard Deviation 8.73	113.5 millimeter of mercury (mmHg) Standard Deviation 9.23
Change From Baseline in Mean Systolic Blood Pressure at Final Assessment Change at Final Assessment (n = 130, 82)	0.9 millimeter of mercury (mmHg) Standard Deviation 9.35	0.3 millimeter of mercury (mmHg) Standard Deviation 9.32

PRIMARY outcome

Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of SPD503. Here, n = number of participants analysed for the specific categories for each arm respectively.

Diastolic Blood pressure was measured at supine and standing position and mean supine diastolic blood pressure was reported here. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=131 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Change From Baseline in Mean Diastolic Blood Pressure at Final Assessment Change at Final Assessment (n = 130, 82)	0.2 millimeter of mercury (mmHg) Standard Deviation 8.96	0.1 millimeter of mercury (mmHg) Standard Deviation 9.55
Change From Baseline in Mean Diastolic Blood Pressure at Final Assessment Baseline (n=131, 83)	64.3 millimeter of mercury (mmHg) Standard Deviation 8.12	66.8 millimeter of mercury (mmHg) Standard Deviation 9.14

PRIMARY outcome

Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of SPD503. Here, n = number of participants analysed for the specific categories for each arm respectively.

Pulse was measured at supine and standing position and mean supine pulse was reported here. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=131 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Change From Baseline in Mean Supine Pulse at Final Assessment Baseline (n = 131, 83)	79.3 beats per minute (bpm) Standard Deviation 11.17	72.1 beats per minute (bpm) Standard Deviation 9.91
Change From Baseline in Mean Supine Pulse at Final Assessment Change at Final Assessment (n = 130, 82)	-7.1 beats per minute (bpm) Standard Deviation 13.52	-2.9 beats per minute (bpm) Standard Deviation 11.71

PRIMARY outcome

Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of SPD503. Here, n = number of participants analysed for the specific categories for each arm respectively.

Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=131 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Change From Baseline in Mean Height at Final Assessment Baseline (n = 131, 83)	142.03 centimeter (cm) Standard Deviation 10.916	166.32 centimeter (cm) Standard Deviation 9.274
Change From Baseline in Mean Height at Final Assessment Change at Final Assessment (n = 128, 79)	8.80 centimeter (cm) Standard Deviation 5.075	5.54 centimeter (cm) Standard Deviation 5.491

PRIMARY outcome

Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of SPD503. Here, n = number of participants analysed for the specific categories for each arm respectively.

Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=131 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Change From Baseline in Mean Weight at Final Assessment Baseline (n = 131, 83)	37.29 kilogram (kg) Standard Deviation 9.256	58.53 kilogram (kg) Standard Deviation 11.478
Change From Baseline in Mean Weight at Final Assessment Change at Final Assessment (n = 128, 79)	8.96 kilogram (kg) Standard Deviation 5.886	6.74 kilogram (kg) Standard Deviation 5.859

PRIMARY outcome

Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of SPD503. Here, n = number of participants analysed for the specific categories for each arm respectively.

Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=131 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Change From Baseline in Electrocardiogram Result (QRS Interval) at Final Assessment Baseline (n=131, 83)	84.9 millisecond (ms) Standard Deviation 7.72	89.7 millisecond (ms) Standard Deviation 6.22
Change From Baseline in Electrocardiogram Result (QRS Interval) at Final Assessment Change at Final Assessment (n=127, 77)	1.8 millisecond (ms) Standard Deviation 6.00	1.8 millisecond (ms) Standard Deviation 6.16

PRIMARY outcome

Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of SPD503. Here, n = number of participants analysed for the specific categories for each arm respectively.

Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=131 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Change From Baseline in Electrocardiogram Result (QT Interval) at Final Assessment Change at Final Assessment (n = 127, 77)	16.9 millisecond (ms) Standard Deviation 27.87	9.5 millisecond (ms) Standard Deviation 29.93
Change From Baseline in Electrocardiogram Result (QT Interval) at Final Assessment Baseline (n = 131, 83)	361.4 millisecond (ms) Standard Deviation 21.40	375.9 millisecond (ms) Standard Deviation 24.93

PRIMARY outcome

Timeframe: Final Assessment (last non missing data/up to Day 714)

Population: Safety Analysis Set included all enrolled participants who took at least 1 dose of SPD503 with number of participants evaluable for this outcome at specific categories.

C-SSRS is a clinician rated assessment of suicidal behavior and / or intent categorized as: Suicidal behavior=a "yes" response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide); Suicidal ideation=a "yes" response to any one of 5 suicidal ideation questions which includes wish to be dead, and 4 different categories of active suicidal ideation (thought, thought with method, thought with intent, thought with plan and intent).

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=131 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Number of Participants With Suicidal Behavior and / or Ideation ("Yes" Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation: Wish to be Dead	0 participants	1 participants
Number of Participants With Suicidal Behavior and / or Ideation ("Yes" Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation: Non-specific Suicidal Thoughts	0 participants	0 participants
Number of Participants With Suicidal Behavior and / or Ideation ("Yes" Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Behaviour: Actual Attempt	0 participants	0 participants
Number of Participants With Suicidal Behavior and / or Ideation ("Yes" Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Behaviour: Non-Suicidal Self-Injurious	0 participants	1 participants
Number of Participants With Suicidal Behavior and / or Ideation ("Yes" Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Behaviour: Interrupted Attempt	0 participants	0 participants
Number of Participants With Suicidal Behavior and / or Ideation ("Yes" Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Behaviour: Aborted Attempt	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

Population: Full Analysis Set included enrolled participants who took at least 1 dose of SPD503, excluding participants from site 403. Here, n = number of participants analysed for the specific categories for each arm respectively.

ADHD-RS-IV was developed to measure the behaviours of children with ADHD with 18 items. Each item is scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items may be grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17) with possible score range from 0 (no symptoms) to 27 (most severe symptoms). The ADHD-RS-IV possible total scores range from 0 (no symptoms) to 54 (most severe symptoms). Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=128 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=81 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Change From Baseline in Attention-deficit and Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) - Total Score at Final Assessment Baseline (n = 127, 81)	40.0 units on a scale Standard Error 0.78	31.2 units on a scale Standard Error 1.19
Change From Baseline in Attention-deficit and Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) - Total Score at Final Assessment Change at Final Assessment (n = 126, 80)	-20.2 units on a scale Standard Error 1.10	-19.3 units on a scale Standard Error 1.31

SECONDARY outcome

Timeframe: Baseline (Day 0) and Final Assessment (last non missing data/up to Day 714)

The CGI-S evaluate each participant's severity and improvement over time. The severity of a participant's condition is rated on a 7-point scale ranging from 1 to 7. The scale measures 0 = Not assessed, 1 = Normal, not at all ill, 2 = Borderline mentally ill (BL-MI), 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severely ill, 7 = Among the most extremely ill participant. Final Assessment is the last valid assessment obtained after Baseline (Visit 2/Day 0) whilst on investigational product and before first dose taper medication (Visit 19/ET/Day 714).

Outcome measures

Outcome measures
Measure	SPD503 (6-12 Years) n=128 Participants Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=81 Participants Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Number of Participants Assessed With Clinical Global Impression Severity of Illness (CGI-S) Scale Baseline: Normal/BL-MI (n=127,81)	0 participants	2 participants
Number of Participants Assessed With Clinical Global Impression Severity of Illness (CGI-S) Scale Baseline: Mildly ill or greater (n=127, 81)	127 participants	79 participants
Number of Participants Assessed With Clinical Global Impression Severity of Illness (CGI-S) Scale Final assessment: Normal/BL-MI (n=127,80)	45 participants	51 participants
Number of Participants Assessed With Clinical Global Impression Severity of Illness (CGI-S) Scale Final Assessment:Mildly ill or greater(n=127,80)	82 participants	29 participants

Adverse Events

SPD503 (6-12 Years)

Serious events: 8 serious events

Other events: 102 other events

Deaths: 0 deaths

SPD503 (13-18 Years)

Serious events: 2 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SPD503 (6-12 Years) n=131 participants at risk Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 participants at risk Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Gastrointestinal disorders Stomatitis	0.76% 1/131 • Number of events 2 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	0.00% 0/83 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Infections and infestations Appendicitis	0.76% 1/131 • Number of events 1 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	0.00% 0/83 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Infections and infestations Gastroenteritis	0.76% 1/131 • Number of events 1 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	0.00% 0/83 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Injury, poisoning and procedural complications Concussion	1.5% 2/131 • Number of events 2 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	0.00% 0/83 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Injury, poisoning and procedural complications Lower limb fracture	0.76% 1/131 • Number of events 1 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	0.00% 0/83 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/131 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	1.2% 1/83 • Number of events 1 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Injury, poisoning and procedural complications Radius fracture	0.76% 1/131 • Number of events 1 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	0.00% 0/83 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Injury, poisoning and procedural complications Upper limb fracture	0.76% 1/131 • Number of events 1 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	0.00% 0/83 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Injury, poisoning and procedural complications Wrist fracture	0.76% 1/131 • Number of events 1 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	0.00% 0/83 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Psychiatric disorders Aggression	0.00% 0/131 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	1.2% 1/83 • Number of events 1 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Reproductive system and breast disorders Testicular torsion	0.76% 1/131 • Number of events 1 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	0.00% 0/83 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	SPD503 (6-12 Years) n=131 participants at risk Participants aged 6-12 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.	SPD503 (13-18 Years) n=83 participants at risk Participants aged 13-18 years received extended-release guanfacine hydrochloride (SPD503) one tablet (1 x 1 mg or 2 mg or 3 mg or 4mg) or two tablets (1 x 2+3 mg or 1 x 2+4 mg, 1 x 3+4 mg) once daily for up to 2 years.
Gastrointestinal disorders Abdominal pain	6.9% 9/131 • Number of events 11 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	4.8% 4/83 • Number of events 4 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Gastrointestinal disorders Abdominal pain upper	6.1% 8/131 • Number of events 11 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	2.4% 2/83 • Number of events 2 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Gastrointestinal disorders Diarrhoea	5.3% 7/131 • Number of events 8 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	3.6% 3/83 • Number of events 3 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Gastrointestinal disorders Nausea	9.2% 12/131 • Number of events 15 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	2.4% 2/83 • Number of events 2 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Gastrointestinal disorders Vomiting	6.1% 8/131 • Number of events 12 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	3.6% 3/83 • Number of events 4 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
General disorders Fatigue	22.9% 30/131 • Number of events 43 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	15.7% 13/83 • Number of events 15 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
General disorders Pyrexia	6.1% 8/131 • Number of events 9 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	2.4% 2/83 • Number of events 2 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Infections and infestations Nasopharyngitis	5.3% 7/131 • Number of events 14 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	21.7% 18/83 • Number of events 24 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Infections and infestations Rhinitis	6.1% 8/131 • Number of events 11 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	3.6% 3/83 • Number of events 3 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Infections and infestations Upper respiratory tract infection	6.9% 9/131 • Number of events 16 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	4.8% 4/83 • Number of events 10 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Nervous system disorders Dizziness	9.2% 12/131 • Number of events 16 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	10.8% 9/83 • Number of events 10 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Nervous system disorders Headache	29.0% 38/131 • Number of events 91 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	27.7% 23/83 • Number of events 43 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Nervous system disorders Somnolence	38.2% 50/131 • Number of events 81 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	32.5% 27/83 • Number of events 37 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Psychiatric disorders Aggression	5.3% 7/131 • Number of events 7 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	2.4% 2/83 • Number of events 2 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Psychiatric disorders Insomnia	7.6% 10/131 • Number of events 10 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	7.2% 6/83 • Number of events 7 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 7/131 • Number of events 8 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)	4.8% 4/83 • Number of events 5 • From the start of the study drug administration up to 9 days after the last dose of study drug administration (up to Week 105)