Trial Outcomes & Findings for Efficacy and Safety of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder (ADHD) (NCT NCT01244490)

NCT ID: NCT01244490

Last Updated: 2021-07-02

Results Overview

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. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 338 participants
• Primary outcome timeframe: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years
• Results posted on: 2021-07-02

Participant Flow

Participant milestones

Measure	Placebo Once daily	Guanfacine Hydrochloride Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Overall Study STARTED	111	115	112
Overall Study COMPLETED	92	91	89
Overall Study NOT COMPLETED	19	24	23

Reasons for withdrawal

Measure	Placebo Once daily	Guanfacine Hydrochloride Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Overall Study Lack of Efficacy	14	5	5
Overall Study Withdrawal by Subject	4	4	9
Overall Study Adverse Event	1	9	5
Overall Study Lost to Follow-up	0	6	3
Overall Study Other	0	0	1

Baseline Characteristics

Efficacy and Safety of Extended-release Guanfacine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)

Baseline characteristics by cohort

Measure	Placebo n=111 Participants Once daily	Guanfacine Hydrochloride n=114 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=112 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)	Total n=337 Participants Total of all reporting groups
Age, Continuous	11.0 Years STANDARD_DEVIATION 2.76 • n=5 Participants	10.9 Years STANDARD_DEVIATION 2.77 • n=7 Participants	10.5 Years STANDARD_DEVIATION 2.81 • n=5 Participants	10.8 Years STANDARD_DEVIATION 2.78 • n=4 Participants
Age, Customized 6-12 years	79 Participants n=5 Participants	81 Participants n=7 Participants	82 Participants n=5 Participants	242 Participants n=4 Participants
Age, Customized 13-17 years	32 Participants n=5 Participants	33 Participants n=7 Participants	30 Participants n=5 Participants	95 Participants n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	38 Participants n=7 Participants	25 Participants n=5 Participants	88 Participants n=4 Participants
Sex: Female, Male Male	86 Participants n=5 Participants	76 Participants n=7 Participants	87 Participants n=5 Participants	249 Participants n=4 Participants
Region of Enrollment AUSTRIA	2 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Region of Enrollment CANADA	6 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants
Region of Enrollment FRANCE	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment GERMANY	23 Participants n=5 Participants	23 Participants n=7 Participants	22 Participants n=5 Participants	68 Participants n=4 Participants
Region of Enrollment IRELAND	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment ITALY	5 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Region of Enrollment POLAND	11 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	37 Participants n=4 Participants
Region of Enrollment ROMANIA	5 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants
Region of Enrollment SPAIN	16 Participants n=5 Participants	18 Participants n=7 Participants	17 Participants n=5 Participants	51 Participants n=4 Participants
Region of Enrollment SWEDEN	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment UKRAINE	21 Participants n=5 Participants	18 Participants n=7 Participants	15 Participants n=5 Participants	54 Participants n=4 Participants
Region of Enrollment UNITED KINGDOM	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment UNITED STATES	18 Participants n=5 Participants	19 Participants n=7 Participants	19 Participants n=5 Participants	56 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set (FAS) defined as all randomized subjects who took at least 1 dose of investigational product. If more than 20% of the items used for summing a score were missing, the score was set to missing.

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. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=111 Participants Once daily	Guanfacine Hydrochloride n=112 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=112 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Week 10/13 - Last Observation Carried Forward (LOCF)	-15.0 units on a scale Standard Error 1.1612	-23.9 units on a scale Standard Error 1.1531	-18.8 units on a scale Standard Error 1.1549

SECONDARY outcome

Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. Not all subjects in the FAS population had data for this outcome.

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. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=111 Participants Once daily	Guanfacine Hydrochloride n=112 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=112 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores	44.1 percentage of participants	67.9 percentage of participants	56.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. If more than 30% of items used to derive the score were missing, the corresponding score was considered as missing.

The WFIRS-P Learning in School Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=100 Participants Once daily	Guanfacine Hydrochloride n=103 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=100 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Learning and School Domain Scores at Week 10/13 - LOCF	-0.419 units on a scale Standard Error 0.0537	-0.636 units on a scale Standard Error 0.0527	-0.581 units on a scale Standard Error 0.0534

SECONDARY outcome

Timeframe: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. If more than 30% of items used to derive the score were missing, the corresponding score was considered as missing.

The WFIRS-P Family Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=106 Participants Once daily	Guanfacine Hydrochloride n=109 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=105 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in the WFIRS-P Family Domain Score at Week 10/13 - LOCF	-0.409 units on a scale Standard Error 0.0568	-0.617 units on a scale Standard Error 0.0558	-0.499 units on a scale Standard Error 0.0566

SECONDARY outcome

Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. Not all subjects in the FAS population had data for this outcome.

CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=111 Participants Once daily	Guanfacine Hydrochloride n=112 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=112 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Clinical Global Impression-Severity of Illness (CGI-S) - LOCF 1 (Normal, not at all ill)	9.9 percentage of participants	14.3 percentage of participants	6.3 percentage of participants
Clinical Global Impression-Severity of Illness (CGI-S) - LOCF 2 (Borderline mentally ill)	15.3 percentage of participants	23.2 percentage of participants	19.6 percentage of participants
Clinical Global Impression-Severity of Illness (CGI-S) - LOCF 3 (Mildly ill)	20.7 percentage of participants	31.3 percentage of participants	32.1 percentage of participants
Clinical Global Impression-Severity of Illness (CGI-S) - LOCF 4 (Moderately ill)	20.7 percentage of participants	22.3 percentage of participants	19.6 percentage of participants
Clinical Global Impression-Severity of Illness (CGI-S) - LOCF 5 (Markedly ill)	25.2 percentage of participants	5.4 percentage of participants	13.4 percentage of participants
Clinical Global Impression-Severity of Illness (CGI-S) - LOCF 6 (Severely ill)	6.3 percentage of participants	3.6 percentage of participants	7.1 percentage of participants
Clinical Global Impression-Severity of Illness (CGI-S) - LOCF 7 (Amongst the most extremely ill)	1.8 percentage of participants	0 percentage of participants	1.8 percentage of participants

SECONDARY outcome

Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. Not all subjects in the FAS population had data for this outcome.

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. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=106 Participants Once daily	Guanfacine Hydrochloride n=110 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=106 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Health Utilities Index-2/3 (HUI 2/3) Scores - LOCF	0.927 units on a scale Standard Deviation 0.0950	0.922 units on a scale Standard Deviation 0.0908	0.913 units on a scale Standard Deviation 0.1052

SECONDARY outcome

Timeframe: Baseline and Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. If more than 30% of items used to derive the score were missing, the corresponding score was considered as missing.

The WFIRS-P Global Score is the mean of 50 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=104 Participants Once daily	Guanfacine Hydrochloride n=110 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=104 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in the WFIRS-P Global Score at Week 10/13 - LOCF	-0.321 units on a scale Standard Error 0.0387	-0.487 units on a scale Standard Error 0.0374	-0.425 units on a scale Standard Error 0.0384

SECONDARY outcome

Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. If more than 30% of items used to derive the score were missing, the corresponding score was considered as missing.

The WFIRS-P Academic Performance Domain is the mean of 4 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=96 Participants Once daily	Guanfacine Hydrochloride n=103 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=101 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in the WFIRS-P Academic Performance Domain Score at Week 10/13 - LOCF	-0.555 units on a scale Standard Error 0.0784	-0.766 units on a scale Standard Error 0.0757	-0.681 units on a scale Standard Error 0.0759

SECONDARY outcome

Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. If more than 30% of items used to derive the score were missing, the corresponding score was considered as missing.

The WFIRS-P Behavior in School Domain is the mean of 6 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=100 Participants Once daily	Guanfacine Hydrochloride n=103 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=100 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in the WFIRS-P Behavior in School Domain Score at Week 10/13 - LOCF	-0.363 units on a scale Standard Error 0.0512	-0.592 units on a scale Standard Error 0.0502	-0.544 units on a scale Standard Error 0.0509

SECONDARY outcome

Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. If more than 30% of items used to derive the score were missing, the corresponding score was considered as missing.

The WFIRS-P Life Skills Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=105 Participants Once daily	Guanfacine Hydrochloride n=110 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=104 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in the WFIRS-P Life Skills Domain Score at Week 10/13 - LOCF	-0.383 units on a scale Standard Error 0.0422	-0.477 units on a scale Standard Error 0.0411	-0.450 units on a scale Standard Error 0.0422

SECONDARY outcome

Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. If more than 30% of items used to derive the score were missing, the corresponding score was considered as missing.

The WFIRS-P Child Self-Concept Domain is the mean of 3 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=101 Participants Once daily	Guanfacine Hydrochloride n=108 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=103 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in the WFIRS-P Child Self-Concept Domain Score at Week 10/13 - LOCF	-0.312 units on a scale Standard Error 0.0544	-0.361 units on a scale Standard Error 0.0528	-0.390 units on a scale Standard Error 0.0536

SECONDARY outcome

Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. If more than 30% of items used to derive the score were missing, the corresponding score was considered as missing.

The WFIRS-P Social Domain is the mean of 7 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=104 Participants Once daily	Guanfacine Hydrochloride n=110 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=104 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in the WFIRS-P Social Domain Score at Week 10/13 - LOCF	-0.322 units on a scale Standard Error 0.0537	-0.555 units on a scale Standard Error 0.0519	-0.434 units on a scale Standard Error 0.0532

SECONDARY outcome

Timeframe: Up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Full Analysis Set. If more than 30% of items used to derive the score were missing, the corresponding score was considered as missing.

The WFIRS-P Risk Domain is the mean of 10 items, ranging from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=99 Participants Once daily	Guanfacine Hydrochloride n=105 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=97 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in the WFIRS-P Risk Domain Score at Week 10/13 - LOCF	-0.134 units on a scale Standard Error 0.0284	-0.190 units on a scale Standard Error 0.0275	-0.173 units on a scale Standard Error 0.0285

SECONDARY outcome

Timeframe: Baseline and up to 10 weeks for children aged 6-12 years and up to 13 weeks for adolescents aged 13-17 years

Population: Safety Population defined as of randomized subjects who took at least 1 dose of investigational product.

The BPRS-C characterizes childhood behavioral and emotional symptomatology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology. Outcome measure is at 10 weeks for ages 6-12 years and at 13 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=102 Participants Once daily	Guanfacine Hydrochloride n=101 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=99 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Weeks 10/13 - LOCF	-5.6 units on a scale Standard Deviation 8.82	-8.3 units on a scale Standard Deviation 8.40	-6.5 units on a scale Standard Deviation 9.23

SECONDARY outcome

Timeframe: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years

Population: Safety Population

The Structured Side-effect Questionnaire is a simple checklist of 17 side effects. The subject indicates whether a side effect has occurred since the last visit by marking 'yes' on the checklist for each of the events listed. Outcome measure is at 12 weeks for ages 6-12 years and at 15 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=111 Participants Once daily	Guanfacine Hydrochloride n=112 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=112 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Structure Side-Effect Questionnaire Nausea	19 participants	30 participants	39 participants
Structure Side-Effect Questionnaire Vomiting	11 participants	7 participants	25 participants
Structure Side-Effect Questionnaire Diarrhea	15 participants	18 participants	8 participants
Structure Side-Effect Questionnaire Abdominal Pain	26 participants	45 participants	42 participants
Structure Side-Effect Questionnaire Decreased Appetite	25 participants	31 participants	48 participants
Structure Side-Effect Questionnaire Increased Appetite	30 participants	40 participants	25 participants
Structure Side-Effect Questionnaire Headache	35 participants	52 participants	34 participants
Structure Side-Effect Questionnaire Dizziness	16 participants	28 participants	23 participants
Structure Side-Effect Questionnaire Fatigue	30 participants	55 participants	35 participants
Structure Side-Effect Questionnaire Nervousnes/Anxiety	25 participants	37 participants	34 participants
Structure Side-Effect Questionnaire Insomnia	19 participants	32 participants	24 participants
Structure Side-Effect Questionnaire Somnolence	26 participants	57 participants	38 participants
Structure Side-Effect Questionnaire Depression	7 participants	7 participants	9 participants
Structure Side-Effect Questionnaire Itching	7 participants	13 participants	10 participants
Structure Side-Effect Questionnaire Rash	4 participants	9 participants	8 participants
Structure Side-Effect Questionnaire Missed Menses	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Up to 12 weeks for children aged 6-12 years and up to 15 weeks for adolescents aged 13-17 years

Population: SP

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. Outcome measure is at 12 weeks for ages 6-12 years and at 15 weeks for ages 13-17 years.

Outcome measures

Measure	Placebo n=111 Participants Once daily	Guanfacine Hydrochloride n=112 Participants Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=112 Participants Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation	2 participants	3 participants	5 participants
Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Behaviour	0 participants	0 participants	0 participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 62 other events

Deaths: 0 deaths

Guanfacine Hydrochloride

Serious events: 1 serious events

Other events: 79 other events

Deaths: 0 deaths

Atomoxetine Hydrochloride

Serious events: 0 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=111 participants at risk Once daily	Guanfacine Hydrochloride n=114 participants at risk Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=112 participants at risk Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Nervous system disorders Syncope	0.90% 1/111 • Number of events 1	0.88% 1/114 • Number of events 1	0.00% 0/112

Other adverse events

Measure	Placebo n=111 participants at risk Once daily	Guanfacine Hydrochloride n=114 participants at risk Tablet, once daily, optimised dose (1mg to 7mg based on age and weight)	Atomoxetine Hydrochloride n=112 participants at risk Capsule, once daily, optimised dose (10mg to 100mg based on weight)
Gastrointestinal disorders Abdominal pain	18.0% 20/111 • Number of events 32	16.7% 19/114 • Number of events 29	17.0% 19/112 • Number of events 31
Gastrointestinal disorders Abdominal pain upper	5.4% 6/111 • Number of events 6	6.1% 7/114 • Number of events 7	1.8% 2/112 • Number of events 3
Gastrointestinal disorders Diarrhoea	13.5% 15/111 • Number of events 18	8.8% 10/114 • Number of events 16	1.8% 2/112 • Number of events 3
Gastrointestinal disorders Nausea	9.9% 11/111 • Number of events 13	15.8% 18/114 • Number of events 19	26.8% 30/112 • Number of events 54
Gastrointestinal disorders Vomiting	7.2% 8/111 • Number of events 9	5.3% 6/114 • Number of events 8	16.1% 18/112 • Number of events 29
General disorders Fatigue	18.0% 20/111 • Number of events 22	25.4% 29/114 • Number of events 45	21.4% 24/112 • Number of events 32
General disorders Pyrexia	3.6% 4/111 • Number of events 4	6.1% 7/114 • Number of events 9	2.7% 3/112 • Number of events 4
Infections and infestations Nasopharyngitis	5.4% 6/111 • Number of events 7	5.3% 6/114 • Number of events 7	2.7% 3/112 • Number of events 3
Metabolism and nutrition disorders Decreased appetite	10.8% 12/111 • Number of events 23	13.2% 15/114 • Number of events 20	27.7% 31/112 • Number of events 44
Metabolism and nutrition disorders Increased appetite	8.1% 9/111 • Number of events 11	10.5% 12/114 • Number of events 15	3.6% 4/112 • Number of events 4
Nervous system disorders Dizziness	8.1% 9/111 • Number of events 9	12.3% 14/114 • Number of events 18	15.2% 17/112 • Number of events 24
Nervous system disorders Headache	24.3% 27/111 • Number of events 46	26.3% 30/114 • Number of events 51	19.6% 22/112 • Number of events 36
Nervous system disorders Somnolence	14.4% 16/111 • Number of events 18	43.9% 50/114 • Number of events 94	17.9% 20/112 • Number of events 32
Psychiatric disorders Anxiety	7.2% 8/111 • Number of events 15	7.9% 9/114 • Number of events 16	6.2% 7/112 • Number of events 18
Psychiatric disorders Insomnia	6.3% 7/111 • Number of events 7	11.4% 13/114 • Number of events 21	7.1% 8/112 • Number of events 10
Psychiatric disorders Nervousness	5.4% 6/111 • Number of events 7	5.3% 6/114 • Number of events 7	5.4% 6/112 • Number of events 6

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

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