Efficacy and Safety of SHP465 at 6.25 mg in the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in Children Aged 6-12 Years

Clinician administered ADHD-RS-5, child, home version total score were analyzed. ADHD-RS-5 consisted of 18 items designed to reflect current symptomatology of ADHD based on diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria. Each item was scored on a 4-point scale ranging from 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items were grouped into 2 subscales: hyperactivity or impulsivity (9 items) and inattentiveness (9 items). Higher total scores indicated higher impairment and lower scores indicated no impairment. Least square (LS) mean was calculated based on restricted maximum likelihood (REML) method of estimation and utilized an unstructured covariance type.

Time frame: Baseline, Week 4

Population: Full analysis set consisted of all participants in the safety set who had baseline ADHD-RS-5 total score and at least 1 postdose ADHD-RS-5 total score. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week.

Time frame: Baseline, Week 4

Population: Safety set consisted of all participants in the randomized set who taken at least 1 dose of investigational product. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week.

Time frame: Baseline, Week 4

Population: Safety set consisted of all participants in the randomized set who taken at least 1 dose of investigational product. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

CGI scale was measured to rate the overall improvement of a participants condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). LS mean was calculated based on restricted maximum likelihood (REML) method of estimation and utilized an unstructured covariance type.

Time frame: Week 4

Population: Full analysis set consisted of all participants in the safety set who had baseline ADHD-RS-5 total score and at least 1 postdose ADHD-RS-5 total score. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

C-SSRS was a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The number of participants with clinical significant change in suicidal ideation and suicidal behavior were reported.

Time frame: Week 4

Population: Safety set consisted of all participants in the randomized set who took at least 1 dose of investigational product. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Clinical laboratory tests included biochemistry, endocrinology, hematology and urinalysis. The investigator assessed out-of-range clinical laboratory values for clinical significance, if the value(s) were not clinically significant or clinically significant.

Time frame: From start of study drug administration up to follow-up (Week 5)

Population: Safety set consisted of all participants in the randomized set who taken at least 1 dose of investigational product.

Participants with clinically significant deviations from baseline values which are deemed clinically significant in the opinion of the investigator were considered in 12-lead ECG and reported.

Time frame: From start of study drug administration up to follow-up (Week 5)

Population: Safety set consisted of all participants in the randomized set who taken at least 1 dose of investigational product.

Vital sign assessments included systolic and diastolic blood pressure and pulse. Participants with clinically significant deviations from baseline values which are deemed clinically significant in the opinion of the investigator were considered as AE's. An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.

Time frame: From start of study drug administration up to follow-up (Week 5)

Population: Safety set consisted of all participants in the randomized set who taken at least 1 dose of investigational product.

The PSQ was a 7-item questionnaire typically used to assess sleep quality with pharmacologic treatment. The questionnaire collected data on average time to sleep, sleep latency, frequency of interrupted sleep, duration of interrupted sleep, total sleep time and sleep quality over the last week. Participants analyzed for number of times woke up per night category were only the participants who responded as yes for the woke up during the night category in this outcome measure.

Time frame: Baseline, Week 4

Population: Safety set consisted of all participants in the randomized set who taken at least 1 dose of investigational product. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have 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 investigational product and no later than 3 days following the last dose of investigational product.

Time frame: From start of study drug administration up to follow-up (Week 5)

Population: Safety set consisted of all participants in the randomized set who as taken at least 1 dose of investigator product.

The CSHQ is a validated, retrospective, parent-reported sleep screening tool. The questionnaire consists of 35 items that yield a TSD score, as well as 8 subscale scores, including bedtime resistance, sleep duration, parasomnias, sleep disordered breathing, night wakings, daytime sleepiness, sleep anxiety, and sleep onset delay. Parents were asked to think of a recent typical week of their child's sleep and to indicate how often sleep disturbance behaviors occurred. A 3-point scale was used for rating: usually if the sleep behavior occurs 5 to 7 times per week, sometimes for 2 to 4 times per week, and rarely for once or not at all during the week. The TSD score, which is the sum of all responses, included all items of the 8 subscales, but consisted of only 33 items because two on the bedtime resistance and sleep anxiety subscales were identical (range: 0, 99). A negative value indicates less sleep disturbance.

Time frame: Week 4

Population: Safety set consisted of all participants in the randomized set who took at least 1 dose of SHP465. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.