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

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.