Trial Outcomes & Findings for Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-deficit/Hyperactivity Disorder (ADHD) (NCT NCT03260205)

Results Overview

ADHD-RS-IV Preschool Version was adapted from the ADHD Rating Scale-IV and provided examples appropriate for the developmental level of preschool children. The ADHD-RS-IV Preschool Version was an 18-item questionnaire that required the respondent to rate the frequency of occurrence of ADHD symptoms as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria. Each item was scored on a 4-point scale ranging from 0 (never or rarely) to 3 (very often) with total scores ranging from 0-54. The 18 items were grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17). Full analysis set (FAS) consisted of all participants in the safety analysis set who had at least 1 post-dose ADHD RS IV preschool version total score assessment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

199 participants

Primary outcome timeframe

Baseline, Week 6

Results posted on

2021-06-08

Participant Flow

The study was conducted at 49 sites in United States between 06 September 2017 (first participant enrolled) and 23 October 2018 (last participant completed).

A total of 284 participants were screened of them 85 participants were screen failures and did not receive any treatment. 199 participants (153 participants for SPD489 treatment and 46 participants for placebo treatment) were randomized, out of them 150 participants completed the study.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	SPD489 5 mg Participants received SPD489 5 mg capsule orally once daily for 6 weeks.	SPD489 10 mg Participants received SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 20 mg Participants received SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 30 mg Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Study STARTED	46	40	37	37	39
Overall Study Received Treatment	45	39	35	34	38
Overall Study COMPLETED	37	32	26	30	25
Overall Study NOT COMPLETED	9	8	11	7	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	SPD489 5 mg Participants received SPD489 5 mg capsule orally once daily for 6 weeks.	SPD489 10 mg Participants received SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 20 mg Participants received SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 30 mg Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Study Adverse Event	2	0	2	2	4
Overall Study Lost to Follow-up	2	2	1	1	5
Overall Study Protocol Violation	0	0	2	0	1
Overall Study Withdrawal by Participant or Parent/LAR	4	5	1	0	2
Overall Study Other: Unspecified	0	0	3	1	1
Overall Study Participant Who Did Not Received AnyDose	1	1	2	3	1

Baseline Characteristics

Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-deficit/Hyperactivity Disorder (ADHD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=45 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	SPD489 5 mg n=39 Participants Participants received SPD489 5 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=35 Participants Participants received SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 20 mg n=34 Participants Participants received SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 30 mg n=38 Participants Participants received SPD489 30 mg capsule orally once daily for 6 weeks.	Total n=191 Participants Total of all reporting groups
Age, Continuous	61.9 months STANDARD_DEVIATION 6.32 • n=5 Participants	60.7 months STANDARD_DEVIATION 6.32 • n=7 Participants	60.9 months STANDARD_DEVIATION 7.18 • n=5 Participants	61.1 months STANDARD_DEVIATION 5.88 • n=4 Participants	61.2 months STANDARD_DEVIATION 7.23 • n=21 Participants	61.2 months STANDARD_DEVIATION 6.54 • n=10 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	10 Participants n=4 Participants	11 Participants n=21 Participants	62 Participants n=10 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	27 Participants n=7 Participants	22 Participants n=5 Participants	24 Participants n=4 Participants	27 Participants n=21 Participants	129 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants	32 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	33 Participants n=7 Participants	24 Participants n=5 Participants	32 Participants n=4 Participants	33 Participants n=21 Participants	159 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race/Ethnicity, Customized Race · White	19 Participants n=5 Participants	17 Participants n=7 Participants	18 Participants n=5 Participants	18 Participants n=4 Participants	17 Participants n=21 Participants	89 Participants n=10 Participants
Race/Ethnicity, Customized Race · Black or African American	23 Participants n=5 Participants	20 Participants n=7 Participants	15 Participants n=5 Participants	15 Participants n=4 Participants	16 Participants n=21 Participants	89 Participants n=10 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants
Race/Ethnicity, Customized Race · Multiple	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	6 Participants n=10 Participants
Race/Ethnicity, Customized Race · Other: Not specified	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	5 Participants n=10 Participants
Race/Ethnicity, Customized Race · Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Full analysis set. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. This outcome was pre-specified to collect and analyze pooled groups of SPD489 doses. The data were planned, analyzed, and reported only for the placebo and the pooled 10, 20, 30 mg doses of SPD489 arms.

ADHD-RS-IV Preschool Version was adapted from the ADHD Rating Scale-IV and provided examples appropriate for the developmental level of preschool children. The ADHD-RS-IV Preschool Version was an 18-item questionnaire that required the respondent to rate the frequency of occurrence of ADHD symptoms as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria. Each item was scored on a 4-point scale ranging from 0 (never or rarely) to 3 (very often) with total scores ranging from 0-54. The 18 items were grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17). Full analysis set (FAS) consisted of all participants in the safety analysis set who had at least 1 post-dose ADHD RS IV preschool version total score assessment.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=84 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6	-9.1 Score on a scale Standard Error 2.36	-14.2 Score on a scale Standard Error 1.57	—	—	—

SECONDARY outcome

Timeframe: Week 6

Population: Full analysis set. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. This outcome was pre-specified to collect and analyze pooled groups of SPD489 doses. The data were planned, analyzed, and reported only for the placebo and the pooled 10, 20, 30 mg doses of SPD489 arms.

CGI-I was an overall assessment of global symptom improvement by evaluation of the participant's condition severity and improvement over time. Scoring was done based on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), where higher score reported worse condition. The scoring was elaborated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. FAS consisted of all participants in the safety analysis set who had at least 1 post-dose ADHD RS IV preschool version total score assessment.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=84 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Clinical Global Impressions Global Improvement (CGI-I) at Week 6	3.4 Score on a scale Standard Error 0.18	2.8 Score on a scale Standard Error 0.13	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Dose response analysis set. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Each SPD489 arm is compared with placebo sequentially, with the highest dose level first.

Dose response relationship was evaluated by using the ADHD-RS Preschool Version Total Score. ADHD-RS-IV Preschool Version was adapted from the ADHD Rating Scale-IV and provided examples appropriate for the developmental level of preschool children. The ADHD-RS-IV Preschool Version was an 18-item questionnaire that requires the respondent to rate the frequency of occurrence of ADHD symptoms as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria. Each item was scored on a 4-point scale ranging from 0 (never or rarely) to 3 (very often) with total scores ranging from 0-54. The 18 items were grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17). Dose response analysis set consisted of all participants in the safety analysis set who had at least 1 valid primary efficacy measurement on the randomized target dose level of the investigational product.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=26 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg n=30 Participants Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=26 Participants Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg n=33 Participants Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Dose Response Relationship for Change From Baseline in ADHD-RS-IV Preschool Version Total Score in Preschool Children at Week 6	-9.1 Score on a scale Standard Error 2.36	-15.3 Score on a scale Standard Error 2.62	-17.0 Score on a scale Standard Error 2.90	-10.8 Score on a scale Standard Error 2.63	-13.5 Score on a scale Standard Error 2.53

SECONDARY outcome

Timeframe: From start of study drug administration up to follow-up (Week 7)

Population: Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a investigational product (IP) and that does not necessarily had a causal relationship with this treatment. TEAEs were defined as AEs that start or deteriorate on or after the date of the first dose of IP and no later than 3 days following the last dose of IP.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=39 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg n=35 Participants Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=34 Participants Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg n=38 Participants Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	19 Participants	13 Participants	15 Participants	18 Participants	22 Participants

SECONDARY outcome

Timeframe: Week 6

Population: Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Vital sign assessments included blood pressure (systolic and diastolic), average pulse rate. Number of participants with potentially clinically significant changes in vital signs were reported. mmHg represents millimetre of mercury in the outcome measure data.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=34 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg n=32 Participants Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=33 Participants Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg n=32 Participants Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Number of Participants With Potentially Clinically Significant Changes in Vital Signs Pulse: >=130 beats per minute (bpm), Week 6	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs Pulse: <=55 bpm, Week 6	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs Systolic Blood Pressure (BP): >=120 mmHg, Week 6	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs Systolic BP: <75 mmHg, Week 6	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs Diastolic BP: >=85 mmHg, Week 6	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs Diastolic BP: <40 mmHg, Week 6	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Height was measured in inche without shoes, with the participant stood on a flat surface and with chin parallel to the floor.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=34 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg n=32 Participants Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=33 Participants Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg n=32 Participants Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Change From Baseline in Height at Week 6	0.7 Centimeter Standard Deviation 1.21	0.7 Centimeter Standard Deviation 1.50	0.7 Centimeter Standard Deviation 1.08	1.0 Centimeter Standard Deviation 1.29	0.5 Centimeter Standard Deviation 1.20

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Body weight was measured in percentile without shoes. Body weight percentile was normalized by sex and age using the Centers for Disease Control and Prevention (CDC) growth charts. Body weight percentiles were categorized as lesser than (\<) 5th, 5th to \< 95th, and greater than or equal to (\>=) 95th percentiles. Change from baseline in body weight at Week 6 was reported.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=34 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg n=32 Participants Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=33 Participants Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg n=32 Participants Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Change From Baseline in Body Weight at Week 6	-1.1 Weight percentile Standard Deviation 5.94	-1.0 Weight percentile Standard Deviation 8.00	-2.8 Weight percentile Standard Deviation 6.37	-4.8 Weight percentile Standard Deviation 9.59	-5.8 Weight percentile Standard Deviation 8.05

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

BMI was derived from height and weight. BMI percentile was normalized by sex and age using the CDC growth charts. BMI percentiles were categorized as: Underweight (BMI \< 5th percentile); Healthy weight (BMI 5th percentile up to \< 85th percentile); Overweight (BMI 85th percentile \< 95th percentile); Obese (BMI \>= 95th percentile). Change from baseline in body mass index at Week 6 was reported.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=34 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg n=32 Participants Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=33 Participants Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg n=32 Participants Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Change From Baseline in Body Mass Index (BMI) at Week 6	-1.6 BMI percentile Standard Deviation 11.17	-0.9 BMI percentile Standard Deviation 14.06	-5.1 BMI percentile Standard Deviation 10.49	-6.7 BMI percentile Standard Deviation 14.28	-7.4 BMI percentile Standard Deviation 11.91

SECONDARY outcome

Timeframe: Week 6

Population: Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure and at the specific categories.

Clinical laboratory evaluations included biochemistry and endocrinology, hematology, and urinalysis. Number of participants with potentially clinically significant changes in clinical laboratory values were reported. ULN in measure data represents upper limit of normal, mcmol/L represents to Micromoles Per Litre, \> = represents greater than or equal to.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=33 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg n=31 Participants Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=30 Participants Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg n=28 Participants Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Eosinophils/Leukocytes: Greater than (>)10%	1 Participants	0 Participants	2 Participants	5 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Lymphocytes/Leukocytes: Greater than (>) 70%	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Neutrophils/Leukocytes: Less than (<) 30%	6 Participants	2 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Platelets: >600x10^9/Litre (L)	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Alanine aminotransferase: >= 3x ULN	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Aspartate aminotransferase: >=3x ULN	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Creatinine: >176.8 mcmol/L or >1.5x ULN	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Glucose: <3.05 Millimole per liter (mmol/L)	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Glucose: >8.88 Millimole per liter (mmol/L)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Potassium: >5.5 Millimole per liter (mmol/L)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Ketones: Positive value (excluding trace)	1 Participants	0 Participants	2 Participants	3 Participants	3 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Occult blood: Positive value (excluding trace)	1 Participants	0 Participants	1 Participants	1 Participants	3 Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values Protein: Positive value (excluding trace)	7 Participants	1 Participants	3 Participants	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Week 6

Population: Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure and at the specific categories.

Number of participants with potentially clinically significant changes in ECG parameters were reported. QTcF interval represents QT Fridericia's Correction Formula interval, QTcB interval represents QTc corrected by Bazett's in measure data.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=34 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg n=31 Participants Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=32 Participants Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg n=32 Participants Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters Heart Rate (< 55 Beats per minute)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters Heart Rate (> 130 Beats per minute)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters QRS Interval (> = 90 millisecond [msec])	1 Participants	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters QT Interval (> = 440 msec)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters QTcB Interval (> =440 msec and <480 msec)	1 Participants	1 Participants	2 Participants	3 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters QTcB Interval (>=480 msec and <500 msec)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters QTcB Interval (>=500 msec)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters QTcF Interval (> =440 msec and <480 msec)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters QTcF Interval (>=480 msec and <500 msec)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters QTcF Interval (>=500 msec)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters ECG Abnormality - Rhythm	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 6

Population: Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure at the specific categories.

Children's Sleep Habits Questionnaire was a tool designed to screen the most common sleep problems in children, and consisted of 33 items for scoring. The instrument evaluated the child's sleep based on behavior within 8 different subscales: bedtime resistance, sleep-onset delay, sleep duration, sleep anxiety, night walkings, parasomnias, sleep-disordered breathing, and daytime sleepiness. Each item receives a score from 1 (problem occurs rarely) to 3 (problem usually occurs); therefore, a higher score is the worse outcome. Scale ranges are as follows: bedtime resistance: 6 to 18, sleep onset delay: 1 to 3, sleep duration: 3 to 9, sleep anxiety: 4 to 12, night walkings: 3 to 9, parasomnias: 7 to 21, sleep-disordered breathing: 3 to 9, daytime sleepiness: 8 to 24, and total disturbance (items from all scales): 33 to 99.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.	Pooled SPD489 Doses (10, 20, and 30 mg) n=39 Participants Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.	SPD489 20 mg n=35 Participants Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.	SPD489 10 mg n=34 Participants Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.	SPD489 5 mg n=38 Participants Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Children's Sleep Habits Questionnaire (CSHQ) at Week 6 Bedtime resistance: Week 6	9.7 Score on scale Standard Deviation 3.22	9.4 Score on scale Standard Deviation 3.30	10.3 Score on scale Standard Deviation 3.36	10.2 Score on scale Standard Deviation 3.60	10.3 Score on scale Standard Deviation 3.30
Children's Sleep Habits Questionnaire (CSHQ) at Week 6 Sleep-onset delay: Week 6	1.7 Score on scale Standard Deviation 0.74	1.7 Score on scale Standard Deviation 0.80	1.8 Score on scale Standard Deviation 0.75	1.8 Score on scale Standard Deviation 0.75	1.8 Score on scale Standard Deviation 0.76
Children's Sleep Habits Questionnaire (CSHQ) at Week 6 Sleep duration: Week 6	3.9 Score on scale Standard Deviation 1.20	3.9 Score on scale Standard Deviation 1.20	3.9 Score on scale Standard Deviation 1.35	4.1 Score on scale Standard Deviation 1.70	4.1 Score on scale Standard Deviation 1.62
Children's Sleep Habits Questionnaire (CSHQ) at Week 6 Sleep anxiety: Week 6	5.7 Score on scale Standard Deviation 2.37	5.8 Score on scale Standard Deviation 2.17	6.5 Score on scale Standard Deviation 2.36	6.5 Score on scale Standard Deviation 2.75	6.4 Score on scale Standard Deviation 2.37
Children's Sleep Habits Questionnaire (CSHQ) at Week 6 Night wakings: Week 6	4.7 Score on scale Standard Deviation 1.78	4.2 Score on scale Standard Deviation 1.23	4.6 Score on scale Standard Deviation 1.58	4.3 Score on scale Standard Deviation 1.36	4.1 Score on scale Standard Deviation 1.39
Children's Sleep Habits Questionnaire (CSHQ) at Week 6 Parasomnias: Week 6	8.6 Score on scale Standard Deviation 1.97	8.9 Score on scale Standard Deviation 1.70	8.8 Score on scale Standard Deviation 1.50	8.2 Score on scale Standard Deviation 1.54	8.4 Score on scale Standard Deviation 1.34
Children's Sleep Habits Questionnaire (CSHQ) at Week 6 Sleep-disordered breathing: Week 6	3.5 Score on scale Standard Deviation 1.00	3.6 Score on scale Standard Deviation 1.02	3.3 Score on scale Standard Deviation 0.68	3.4 Score on scale Standard Deviation 0.70	3.5 Score on scale Standard Deviation 0.95
Children's Sleep Habits Questionnaire (CSHQ) at Week 6 Daytime sleepiness: Week 6	10.9 Score on scale Standard Deviation 3.58	10.9 Score on scale Standard Deviation 3.33	10.3 Score on scale Standard Deviation 3.33	9.8 Score on scale Standard Deviation 3.57	12.4 Score on scale Standard Deviation 4.46

SECONDARY outcome

Timeframe: Up to Week 6

Population: Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

C-SSRS was semi-structured interview that captured the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview included definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. The C-SSRS contained 2 required items pertaining to suicidal ideation, 4 required items pertaining to suicidal behavior, and 1 required item pertaining to non-suicidal but self-injurious behavior. In situations where there was a positive response to the screening questions, there were 8 additional suicidal ideation items and 4 additional suicidal behavior items which were completed. Thus, there was a maximum of 19 items to be completed. Here number of participants responded as yes to suicidal ideation or behaviour were reported.