Safety, Tolerability and Pharmacokinetics of SHP465 in Children Aged 4 to 5 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03327402
• Collaborator: (none)
• Enrollment: 24
• Locations: 8
• Arm: 1
• Actual Duration (Months): 6.8
• Patients Per Site: 3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of SHP465 in children aged 4 to 5 years with ADHD after multiple daily doses of 6.25 milligram (mg) SHP465

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder (ADHD)	Drug: SHP465	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Open-label Study of the Safety, Tolerability, and Pharmacokinetics of d- and l-Amphetamine After Multiple Daily Doses of SHP465 6.25 mg Administered in Children Aged 4 to 5 Years With Attention-Deficit/Hyperactivity Disorder
• Actual Study Start Date: Mar 13, 2018
• Actual Primary Completion Date: Oct 5, 2018
• Actual Study Completion Date: Oct 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SHP465 Participants will receive SHP465 capsule at a dose of 6.25 mg, orally once daily for 4 weeks.	Drug: SHP465; SHP465 capsule will be administered at a dose of 6.25 mg, orally once daily for 4 weeks. SHP465 is comprised of sulfate salts of dextroamphetamine and amphetamine, with dextroamphetamine saccharate and amphetamine aspartate monohydrate, which provide a composite enantiomer ratio of 3:1 d-amphetamine to l-amphetamine.

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Drug Concentration (Cmax) Occurred at the Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Plasma Dextroamphetamine (d-Amphetamine) and Plasma Levoamphetamine (l-Amphetamine) [Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

   Maximum plasma drug concentration occurred at time of maximum observed concentration of plasma d-amphetamine and plasma l-amphetamine during a dosing interval were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

2. Trough Plasma Drug Concentration Ctrough at Steady State (Ctrough,ss) of Plasma d-Amphetamine and Plasma l-Amphetamine [Predose on Day 1 and Day 28 and at 24 hours (Day 29) postdose on Day 28]

   Trough plasma drug concentration (predose concentrations collected at steady state) of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

3. Time to Reach Maximum Observed Plasma Drug Concentration (Tmax) During Dosing Interval of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

   Time to reach maximum observed plasma drug concentration of plasma d-amphetamine and plasma l-amphetamine during a dosing interval were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

4. Area Under the Concentration-Time Curve From Time Zero to the Last Timepoint (AUC0-t) During Sample Collection of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

   Area under the concentration-time curve from time zero to the last quantifiable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

5. Area Under the Concentration-Time Curve From Time Zero Predose to Five Hours Postdose (AUC0-5) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: Predose, 2, 5 hours Postdose on Day 7]

   Area under the concentration time curve from time zero predose to five hours postdose of plasma d-amphetamine and plasma d-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

6. Area Under the Concentration Time Curve From Time Five Hours to the Last Timepoint (AUC5-t) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

   Area under the concentration time curve from time five hours to the time of last quantifiable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.

7. Area Under the Concentration-Time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

   Area under the concentration-time curve from time of dosing to the last measurable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

8. Area Under the Concentration-Time Curve Over the Dosing Interval (24 Hours) at Steady State (AUCtau,ss) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

   Area under the concentration-time curve over the dosing interval (24 hours) at steady state of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

9. Terminal Rate Constant (Lambda z) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

   Terminal Rate Constant of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.

10. Total Body Clearance (CL/F) for Extravascular Administration of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

    Apparent total clearance of the plasma drug concentration of plasma d- amphetamine and plasma l-amphetamine after oral dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.

11. Terminal Half-life (t1/2) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

    Time required for the plasma drug concentration to reach half of its original value of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.

12. Apparent Volume of Distribution (Vss/F) at Steady State of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7]

    Apparent volume of distribution at steady state of plasma d-amphetamine and plasma l-amphetamine after oral dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.

13. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From start of study drug administration up to follow-up (up to 5 weeks)]

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

14. Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs [From start of study drug administration up to follow-up (up to 5 weeks)]

    Vital sign assessments included blood pressure, pulse, respiratory rate and body temperature. Any change in vital signs which were deemed clinically significant by the investigator were recorded as TEAE.

15. Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs [From start of study drug administration up to follow-up (up to 5 weeks)]

    12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported as TEAE.

16. Change From Baseline in Height at Final On-Treatment Assessment [FoTA (up to Day 30)]

    Height (in centimeters) was measured using a stadiometer with the participant standing on a flat surface without shoes and with the chin parallel to the floor. Final on-treatment assessment (FoTA) was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).

17. Change From Baseline in Weight at Final On-Treatment Assessment [FoTA (up to Day 30)]

    Weight (in kilograms) was measured using a calibrated scale. Participant should be in light clothes and without shoes. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).

18. Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Reported as TEAEs [From start of study drug administration up to follow-up (up to 5 weeks)]

    Clinical laboratory tests included biochemistry, endocrinology, hematology and urinalysis. Any change in clinical laboratory results which are deemed clinically significant by the investigator were reported as TEAE.

19. Number of Participants With Overall Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment [FoTA (up to Day 30)]

    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. The assessment was done by the nature of the responses, not by a numbered scale. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).

20. Length of Time Awake Per Night Assessed by PSQ at Final On-Treatment Assessment [FoTA (up to Day 30)]

    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. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).

21. Length of Time to Fall Asleep Per Night Assessed by PSQ at Final On-Treatment Assessment [FoTA (up to Day 30)]

    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. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).

22. Length of Time Sleeping Per Night Assessed by PSQ at Final On-Treatment Assessment [FoTA (up to Day 30)]

    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. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).

23. Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Final On-Treatment Assessment [FoTA (up to Day 30)]

    The CSHQ was a validated, retrospective, parent-reported sleep screening tool. The questionnaire consisted 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. Each item receives a score from 1 (meaning the problem occurs rarely) to 3 (meaning the 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 Wakings: 3 to 9, Parasomnias: 7 to 21, Disordered Breathing: 3 to 9, Daytime Sleepiness: 8 to 24, and Total Disturbance (items from all scales): 33 to 99. A negative value indicated less sleep disturbance.

24. Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Final On-Treatment Assessment [FoTA (up to Day 30)]

    C-SSRS was a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts (suicidal ideation) and suicidal behaviors during the assessment period needed to be determine if a suicide-related thought or behavior were occurred. The assessment was done by the nature of the responses, not by a numbered scale. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).

Secondary Outcome Measures

1. Observed Analyte Concentration at 12 Hours After Dose Administration (C12) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: 12 hours (Day 8) Postdose on Day 7]

   Observed analyte concentration of plasma d-amphetamine and plasma l-amphetamine at 12 hours after dose administration were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

2. Observed Analyte Concentration at 16 Hours After Dose Administration (C16) of Plasma d-Amphetamine and Plasma l- Amphetamine [Week 4: 16 hours (Day 8) Postdose on Day 7]

   Observed analyte concentration of plasma d-amphetamine and plasma l-amphetamine at 16 hours after dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.

3. Observed Analyte Concentration at 24 Hours After Dose Administration (C24) of Plasma d-Amphetamine and Plasma l- Amphetamine [Week 4: 24 hours (Day 8) Postdose on Day 7]

   Observed analyte concentration of plasma d-amphetamine and plasma l-amphetamine at 24 hours after dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.

4. Area Under the Concentration-Time Curve From Time Five Hours to Twelve Hours Postdose (AUC5-12) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: 5, 8, 12 hours Postdose on Day 7]

   Area under the concentration-time curve from time five hours to twelve hours postdose (AUC5-12) in plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.

5. Area Under the Concentration-Time Curve From Time Twelve Hours to Sixteen Hours Postdose (AUC12-16) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: 12, 16 hours Postdose on Day 7]

   Area under the concentration-time curve from time twelve hours to sixteen hours postdose (AUC12-16) in plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

6. Area Under the Concentration-Time Curve From Time Sixteen Hours to Twenty-Four Hours Postdose (AUC16-24) of Plasma d-Amphetamine and Plasma l-Amphetamine [Week 4: 16, 24 hours (Day 8) Postdose on Day 7]

   Area under the concentration-time curve from time sixteen hours to twenty-four hours postdose (AUC16-24) in plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 5 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female aged 4-5 years inclusive at the time of consent with a primary diagnosis of ADHD (any subtype) based on a detailed psychiatric evaluation using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and has undergone nonpharmacological treatment or has a severe enough condition to consider enrollment without undergoing prior nonpharmacological treatment, based on the investigator's judgment or has never taken ADHD medication or has taken ADHD medication with unacceptable efficacy and/or tolerability.

2. Participant's parent/legally authorized representative (LAR) must sign the informed consent form, and there must be documentation of assent (if applicable) and is willing and able to fully comply with all of the testing and requirements defined in the protocol.

3. Participant during the screening period:

1. Has a total score of ADHD-RS-5 >=28 for boys and >=24 for girls. ii. Has a Clinical Global Impressions-Severity of Illness (CGI-S) score >=4. iii.Functions at an age-appropriate level intellectually, as determined by the investigator.

1. Participant has the ability to take investigational product by either swallowing the capsule whole or sprinkling the capsule contents in applesauce and ingesting the entire mixture immediately without chewing.

2. Participant has lived with the same parent/LAR for at least 6 months.

Exclusion Criteria:

1. Prior enrollment or participation in the study.

2. Documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.

3. Participant cannot swallow a pill and/or applesauce, or has an allergy to applesauce.

4. Participant is currently taking or has taken ADHD medication with acceptable efficacy and tolerability.

5. Participant has taken ADHD medication within 7 days prior to the administration of investigational product.

6. Participant has used any medication (including over-the-counter, herbal, or homeopathic preparations) within 30 days prior to the administration of investigational product or 5 half-lives, whichever is longer, with the exception of the following:

1. Thyroid medication ii. Intermittent use of nonsteroidal anti-inflammatory drugs or acetaminophen iii. As needed use of a beta-agonists inhaler for mild asthma or exercise induced bronchospasm iv. Over-the-counter nonsedating antihistamines for allergies. v. Participant has continuously used oral corticosteroids >=7 days in 3 months prior to investigational product dosing. If continuous use was less than (<) 7 days, 1 month of washout prior to dosing of investigational product is required.

1. Within 30 days prior to the administration of investigational product (IP):

1. Participant has used an IP.

1. If the elimination half-life of the previous study's IP was less than 6 days, then the last dose of the previous IP should be 30 days prior to the first dose of SHP465.

2. If the elimination half-life of the previous study's IP was greater than 6 days, then the last dose of the previous IP should be 5 half-lives prior to the dose of SHP465.

3. Glaucoma.

4. Known family history of sudden cardiac death or ventricular arrhythmia.

5. Known history of symptomatic cardiovascular disease, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac conditions placing them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

6. Any clinically significant ECG or clinically significant laboratory abnormalities at the first screening visit based on the investigator's judgment. A single retest of laboratory parameters is allowed based on the investigator's judgment.

7. Marfan's syndrome.

8. Blood pressure >= 95th percentile for age, sex, and height at the screening visit.

9. Height and weight <= 5th percentile for age and sex at the first screening visit.

10. Current abnormal thyroid function test results, defined as abnormal thyroid-stimulating hormone, thyroxine (T4), and tri-iodothyronine (T3) at the first screening visit. Treatment with a stable dose of thyroid medication for at least 3 months is permitted.

11. History of seizures (other than infantile febrile seizures).

12. Current, controlled (requiring medication or therapy) or uncontrolled, comorbid psychiatric disorder including but not limited to any of the following comorbid Axis I disorders and Axis II disorders.

13. Currently considered a suicide risk in the opinion of the investigator, has previously made a suicide attempt, or has a prior history of or is currently demonstrating active suicidal ideation.

14. History of physical, sexual, or emotional abuse.

15. Primary sleep disorder (eg, sleep apnea, narcolepsy).

16. Eating disorder.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Preferred Research Partners	Little Rock	Arkansas	United States	72211
2	Clinical Neuroscience Solutions Inc	Orlando	Florida	United States	32801
3	Qualmedica Research, LLC	Evansville	Indiana	United States	47715
4	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
5	Ohio Pediatric Research Assn Inc	Dayton	Ohio	United States	45414
6	Professional Psychiatric Services (PPS)	Mason	Ohio	United States	45040
7	Coastal Pediatric Associates	Mount Pleasant	South Carolina	United States	29464
8	Clinical Neuroscience Solutions Inc	Memphis	Tennessee	United States	38119

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Sep 15, 2017
• Statistical Analysis Plan - Apr 2, 2018

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT03327402
• Other Study ID Numbers: SHP465-112
• First Posted: Oct 31, 2017
• Last Update Posted: Jun 8, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Shire: SHP465; ADHD; Hyperactivity
• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity

Study Results

Participant Flow

Recruitment Details	The study was conducted at eight centers in the United States between 13 March 2018 (first participant first visit) and 05 October 2018 (last participant last visit).
Pre-assignment Detail	A total of 24 participants were enrolled and received the treatment. Of them 12 participants were included in the rich pharmacokinetic (PK) sampling group and 12 participants were included in the sparse PK sampling group. Overall, 22 participants completed the study.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Period Title: Overall Study
STARTED	24
Rich PK Sampling Group	12
Sparse PK Sampling Group	12
COMPLETED	22
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Overall Participants	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	4.8 (0.41)
Sex: Female, Male (Count of Participants)
Female	8 33.3%
Male	16 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	24 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	12 50%
White	12 50%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Drug Concentration (Cmax) Occurred at the Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of Plasma Dextroamphetamine (d-Amphetamine) and Plasma Levoamphetamine (l-Amphetamine)
Description	Maximum plasma drug concentration occurred at time of maximum observed concentration of plasma d-amphetamine and plasma l-amphetamine during a dosing interval were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	31.37 (32.6)
l-Amphetamine	9.895 (34.7)

2. Primary Outcome

Title	Trough Plasma Drug Concentration Ctrough at Steady State (Ctrough,ss) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Trough plasma drug concentration (predose concentrations collected at steady state) of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Predose on Day 1 and Day 28 and at 24 hours (Day 29) postdose on Day 28

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	7.934 (6.3077)
l-Amphetamine	3.092 (2.5253)

3. Primary Outcome

Title	Time to Reach Maximum Observed Plasma Drug Concentration (Tmax) During Dosing Interval of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Time to reach maximum observed plasma drug concentration of plasma d-amphetamine and plasma l-amphetamine during a dosing interval were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one post-dose PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	7.917
l-Amphetamine	7.917

4. Primary Outcome

Title	Area Under the Concentration-Time Curve From Time Zero to the Last Timepoint (AUC0-t) During Sample Collection of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Area under the concentration-time curve from time zero to the last quantifiable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	646.3 (27.5)
l-Amphetamine	222.1 (31.1)

5. Primary Outcome

Title	Area Under the Concentration-Time Curve From Time Zero Predose to Five Hours Postdose (AUC0-5) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Area under the concentration time curve from time zero predose to five hours postdose of plasma d-amphetamine and plasma d-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5 hours Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one post-dose PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	109.7 (36.1)
l-Amphetamine	34.53 (40.3)

6. Primary Outcome

Title	Area Under the Concentration Time Curve From Time Five Hours to the Last Timepoint (AUC5-t) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Area under the concentration time curve from time five hours to the time of last quantifiable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	549.9 (30.3)
l-Amphetamine	194.1 (34.1)

7. Primary Outcome

Title	Area Under the Concentration-Time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Area under the concentration-time curve from time of dosing to the last measurable concentration of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	646.3 (27.5)
l-Amphetamine	222.1 (31.1)

8. Primary Outcome

Title	Area Under the Concentration-Time Curve Over the Dosing Interval (24 Hours) at Steady State (AUCtau,ss) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Area under the concentration-time curve over the dosing interval (24 hours) at steady state of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	520.6 (29.8)
l-Amphetamine	171.0 (32.9)

9. Primary Outcome

Title	Terminal Rate Constant (Lambda z) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Terminal Rate Constant of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure at the specific categories. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	12
d-Amphetamine	0.06639 (15.5)
l-Amphetamine	0.05632 (15.3)

10. Primary Outcome

Title	Total Body Clearance (CL/F) for Extravascular Administration of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Apparent total clearance of the plasma drug concentration of plasma d- amphetamine and plasma l-amphetamine after oral dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	5.618 (29.8)
l-Amphetamine	5.703 (32.9)

11. Primary Outcome

Title	Terminal Half-life (t1/2) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Time required for the plasma drug concentration to reach half of its original value of plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure at the specific categories. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	12
d-Amphetamine	9.911
l-Amphetamine	12.16

12. Primary Outcome

Title	Apparent Volume of Distribution (Vss/F) at Steady State of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Apparent volume of distribution at steady state of plasma d-amphetamine and plasma l-amphetamine after oral dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: Predose, 2, 5, 8, 12, 16, 24 hours (Day 8), 48 hours (Day 9) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected.Here, number of participants analyzed signifies participants who were evaluable for this outcome measure at the specific categories. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	12
d-Amphetamine	90.09 (34.3)
l-Amphetamine	109.4 (35.6)

13. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily had a causal relationship with this treatment. TEAEs was defined as AEs that start or deteriorate on or after the date of the first dose of investigational product (IP) and no later than 3 days following the last dose of IP.
Time Frame	From start of study drug administration up to follow-up (up to 5 weeks)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
Count of Participants [Participants]	11 45.8%

14. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
Description	Vital sign assessments included blood pressure, pulse, respiratory rate and body temperature. Any change in vital signs which were deemed clinically significant by the investigator were recorded as TEAE.
Time Frame	From start of study drug administration up to follow-up (up to 5 weeks)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
Count of Participants [Participants]	1 4.2%

15. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs
Description	12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported as TEAE.
Time Frame	From start of study drug administration up to follow-up (up to 5 weeks)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
Count of Participants [Participants]	0 0%

16. Primary Outcome

Title	Change From Baseline in Height at Final On-Treatment Assessment
Description	Height (in centimeters) was measured using a stadiometer with the participant standing on a flat surface without shoes and with the chin parallel to the floor. Final on-treatment assessment (FoTA) was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Time Frame	FoTA (up to Day 30)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	22
Mean (Standard Deviation) [centimeter (cm)]	1.601 (1.5073)

17. Primary Outcome

Title	Change From Baseline in Weight at Final On-Treatment Assessment
Description	Weight (in kilograms) was measured using a calibrated scale. Participant should be in light clothes and without shoes. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Time Frame	FoTA (up to Day 30)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
Mean (Standard Deviation) [kilogram (kg)]	-0.305 (0.4268)

18. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Reported as TEAEs
Description	Clinical laboratory tests included biochemistry, endocrinology, hematology and urinalysis. Any change in clinical laboratory results which are deemed clinically significant by the investigator were reported as TEAE.
Time Frame	From start of study drug administration up to follow-up (up to 5 weeks)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
Count of Participants [Participants]	0 0%

19. Primary Outcome

Title	Number of Participants With Overall Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Final On-Treatment Assessment
Description	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. The assessment was done by the nature of the responses, not by a numbered scale. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Time Frame	FoTA (up to Day 30)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
FoTA: Overall quality of sleep - Very poor	0 0%
FoTA: Overall quality of sleep - Poor	4 16.7%
FoTA: Overall quality of sleep - Average	6 25%
FoTA: Overall quality of sleep - Good	11 45.8%
FoTA: Overall quality of sleep - Very Good	3 12.5%

20. Primary Outcome

Title	Length of Time Awake Per Night Assessed by PSQ at Final On-Treatment Assessment
Description	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. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Time Frame	FoTA (up to Day 30)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	14
Mean (Standard Deviation) [minutes]	10.1 (9.86)

21. Primary Outcome

Title	Length of Time to Fall Asleep Per Night Assessed by PSQ at Final On-Treatment Assessment
Description	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. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Time Frame	FoTA (up to Day 30)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
Mean (Standard Deviation) [minutes]	19.8 (11.75)

22. Primary Outcome

Title	Length of Time Sleeping Per Night Assessed by PSQ at Final On-Treatment Assessment
Description	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. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Time Frame	FoTA (up to Day 30)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
Mean (Standard Deviation) [hours]	9.1 (1.41)

23. Primary Outcome

Title	Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Final On-Treatment Assessment
Description	The CSHQ was a validated, retrospective, parent-reported sleep screening tool. The questionnaire consisted 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. Each item receives a score from 1 (meaning the problem occurs rarely) to 3 (meaning the 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 Wakings: 3 to 9, Parasomnias: 7 to 21, Disordered Breathing: 3 to 9, Daytime Sleepiness: 8 to 24, and Total Disturbance (items from all scales): 33 to 99. A negative value indicated less sleep disturbance.
Time Frame	FoTA (up to Day 30)

Outcome Measure Data

Analysis Population Description

Safety set consisted of all enrolled participants who had taken at least one dose of investigational product. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
FoTA: Total Sleep Disturbance Score	45.4 (8.21)
FoTA: Bedtime Resistance	10.1 (3.71)
FoTA: Sleep Onset Delay	1.4 (0.58)
FoTA: Sleep Duration	4.3 (1.68)
FoTA: Sleep Anxiety	6.2 (2.41)
FoTA: Night Wakings	4.1 (0.90)
FoTA: Parasomnias	8.9 (2.12)
FoTA: Sleep Disordered Breathing	3.2 (0.82)
FoTA: Daytime Sleepiness	10.6 (3.02)

24. Primary Outcome

Title	Number of Participants With a Positive Response in Columbia-Suicide Severity Rating Scale (C-SSRS) at Final On-Treatment Assessment
Description	C-SSRS was a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts (suicidal ideation) and suicidal behaviors during the assessment period needed to be determine if a suicide-related thought or behavior were occurred. The assessment was done by the nature of the responses, not by a numbered scale. FoTA was defined as the last valid assessment obtained after baseline and while on IP (on or before 2 days after the last dose date).
Time Frame	FoTA (up to Day 30)

Outcome Measure Data

Analysis Population Description

Safety Set consisted of all enrolled participants who had taken at least one dose of investigational product.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	24
Suicidal Ideation	0 0%
Suicidal Behavior	0 0%

25. Secondary Outcome

Title	Observed Analyte Concentration at 12 Hours After Dose Administration (C12) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Observed analyte concentration of plasma d-amphetamine and plasma l-amphetamine at 12 hours after dose administration were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: 12 hours (Day 8) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	24.59 (31.1)
l-Amphetamine	8.059 (33.2)

26. Secondary Outcome

Title	Observed Analyte Concentration at 16 Hours After Dose Administration (C16) of Plasma d-Amphetamine and Plasma l- Amphetamine
Description	Observed analyte concentration of plasma d-amphetamine and plasma l-amphetamine at 16 hours after dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: 16 hours (Day 8) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	20.53 (39.0)
l-Amphetamine	6.957 (40.7)

27. Secondary Outcome

Title	Observed Analyte Concentration at 24 Hours After Dose Administration (C24) of Plasma d-Amphetamine and Plasma l- Amphetamine
Description	Observed analyte concentration of plasma d-amphetamine and plasma l-amphetamine at 24 hours after dose administration were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: 24 hours (Day 8) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	11.16 (28.5)
l-Amphetamine	4.186 (32.7)

28. Secondary Outcome

Title	Area Under the Concentration-Time Curve From Time Five Hours to Twelve Hours Postdose (AUC5-12) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Area under the concentration-time curve from time five hours to twelve hours postdose (AUC5-12) in plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method.Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: 5, 8, 12 hours Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	195.2 (32.6)
l-Amphetamine	61.88 (34.4)

29. Secondary Outcome

Title	Area Under the Concentration-Time Curve From Time Twelve Hours to Sixteen Hours Postdose (AUC12-16) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Area under the concentration-time curve from time twelve hours to sixteen hours postdose (AUC12-16) in plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: 12, 16 hours Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	89.68 (31.7)
l-Amphetamine	29.92 (34.4)

30. Secondary Outcome

Title	Area Under the Concentration-Time Curve From Time Sixteen Hours to Twenty-Four Hours Postdose (AUC16-24) of Plasma d-Amphetamine and Plasma l-Amphetamine
Description	Area under the concentration-time curve from time sixteen hours to twenty-four hours postdose (AUC16-24) in plasma d-amphetamine and plasma l-amphetamine were evaluated using rich sampling collection method. Values displayed do not necessarily reflect the actual precision obtained.
Time Frame	Week 4: 16, 24 hours (Day 8) Postdose on Day 7

Outcome Measure Data

Analysis Population Description

PK set consisted of all participants in the safety set for whom at least one PK blood sample was collected. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Sparse PK sampling group were excluded from the PK analysis.

Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
Measure Participants	11
d-Amphetamine	122.1 (31.3)
l-Amphetamine	43.44 (34.0)

Adverse Events

Time Frame	From start of study drug administration up to follow-up (up to 5 weeks)
Arm/Group Title	SHP465
Arm/Group Description	Participants aged 4-5 years received SHP465 capsule at a dose of 6.25 milligram (mg) orally once daily for 4 weeks.
All Cause Mortality
	SHP465
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Serious Adverse Events
	SHP465
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Other (Not Including Serious) Adverse Events
	SHP465
	Affected / at Risk (%)	# Events
Total	2/24 (8.3%)
Psychiatric disorders
Affect lability	2/24 (8.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.