Trial Outcomes & Findings for Efficacy and Safety of SHP465 at 6.25 mg in the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in Children Aged 6-12 Years (NCT NCT03325881)

Last Updated: 2021-06-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

89 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2021-06-02

Participant Flow

The study was conducted at 43 study centers in the United States between 09 December 2017 (first participant first visit) and 07 June 2018 (last participant last visit).

A total of 124 participants were screened, of them 89 were randomized and 88 received the treatment. Out of them, 83 participants completed the study.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 Participants received 6.25 milligrams (mg) SHP465 capsule orally once daily for 4 weeks.
Overall Study STARTED	44	45
Overall Study Treated	43	45
Overall Study COMPLETED	41	42
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 Participants received 6.25 milligrams (mg) SHP465 capsule orally once daily for 4 weeks.
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	0	2
Overall Study Lack of Efficacy	2	0
Overall Study Not treated	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=43 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=45 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.	Total n=88 Participants Total of all reporting groups
Age, Continuous	8.8 Years STANDARD_DEVIATION 2.03 • n=5 Participants	8.8 Years STANDARD_DEVIATION 2.20 • n=7 Participants	8.8 Years STANDARD_DEVIATION 2.11 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	18 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	27 Participants n=7 Participants	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	20 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	28 Participants n=5 Participants	30 Participants n=7 Participants	58 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=42 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) Total Score at Week 4	-9.7 Score on a scale Interval -13.2 to -6.2	-11.6 Score on a scale Interval -15.0 to -8.2

SECONDARY outcome

Timeframe: Week 4

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.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=42 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Clinical Global Impression of Improvement (CGI-I) at Week 4	3.3 Score on a scale Interval 3.0 to 3.6	3.2 Score on a scale Interval 2.9 to 3.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=45 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	7 Participants	11 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=45 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Number of Participants With Clinically Significant Change in Vital Signs Were Reported as Adverse Event (AE) Number of participants with secondary hypertension	1 Participants	0 Participants
Number of Participants With Clinically Significant Change in Vital Signs Were Reported as Adverse Event (AE) Number of participants with Tachycardia	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=45 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Number of Participants With Clinically Significant Change in Clinical Laboratory Test Results Assessed by the Investigator	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=45 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Assessed by the Investigator	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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. 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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=42 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Woke up during the night - Yes	20 Participants	14 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Woke up during the night - No	23 Participants	28 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Woke up during the night - Yes	13 Participants	11 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Woke up during the night - No	27 Participants	31 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Number of times woke up per night = 0	0 Participants	1 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Number of times woke up per night = 1	12 Participants	6 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Number of times woke up per night = 2	8 Participants	6 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Number of times woke up per night = 3	0 Participants	1 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Number of times woke up per night = 4	0 Participants	0 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Number of times woke up per night >= 5	0 Participants	0 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Number of times woke up per night = 0	0 Participants	1 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Number of times woke up per night = 1	8 Participants	8 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Number of times woke up per night = 2	5 Participants	1 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Number of times woke up per night = 3	0 Participants	0 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Number of times woke up per night = 4	0 Participants	1 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Number of times woke up per night >= 5	0 Participants	0 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Was the past week a typical week - Yes	39 Participants	36 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Was the past week a typical week - No	4 Participants	6 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Was the past week a typical week - Yes	36 Participants	36 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Was the past week a typical week - No	4 Participants	6 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Past week was not typical - Vacation	2 Participants	2 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Past week was not typical - School break	1 Participants	2 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Past week was not typical - Friend house	0 Participants	0 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Past week was not typical - ill	0 Participants	0 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Past week was not typical - other	1 Participants	2 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Past week was not typical - Vacation	0 Participants	0 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Past week was not typical - School break	3 Participants	3 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Past week was not typical - Friend house	0 Participants	0 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Past week was not typical - ill	0 Participants	1 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Past week was not typical - other	1 Participants	2 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline : Overall quality - Better than usual	0 Participants	1 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Overall quality - Same as usual	6 Participants	7 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Baseline: Overall quality - Worse than usual	2 Participants	1 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Overall quality - Better than usual	1 Participants	2 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Overall quality - Same as usual	4 Participants	7 Participants
Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4 Week 4: Overall quality - Worse than usual	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline, Week 4

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=45 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Change From Baseline in Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by PSQ at Week 4 Baseline: Length of Time to fall asleep per night	27.0 minutes Standard Deviation 20.25	27.2 minutes Standard Deviation 21.51
Change From Baseline in Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by PSQ at Week 4 Week 4: Length of Time to fall asleep per night	19.3 minutes Standard Deviation 16.13	21.0 minutes Standard Deviation 14.35
Change From Baseline in Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by PSQ at Week 4 Baseline: Length of Time awake per night	12.4 minutes Standard Deviation 8.41	8.0 minutes Standard Deviation 7.63
Change From Baseline in Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by PSQ at Week 4 Week 4: Length of Time awake per night	8.9 minutes Standard Deviation 5.18	15.1 minutes Standard Deviation 17.01

SECONDARY outcome

Timeframe: Baseline, Week 4

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=45 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Change From Baseline in Length of Time Sleeping Per Night Assessed by PSQ at Week 4 Baseline	8.9 hours Standard Deviation 1.20	8.8 hours Standard Deviation 1.22
Change From Baseline in Length of Time Sleeping Per Night Assessed by PSQ at Week 4 Week 4	9.1 hours Standard Deviation 1.34	8.9 hours Standard Deviation 1.16

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=41 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Week 4	42.7 Units on scale Standard Deviation 9.36	42.8 Units on scale Standard Deviation 9.17

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=45 Participants Participants received 6.25 mg SHP465 capsule orally once daily for 4 weeks.
Number of Participants With a Positive Response in Columbia-suicide Severity Rating Scale (C-SSRS) at Week 4 Suicidal Ideation	0 Participants	0 Participants
Number of Participants With a Positive Response in Columbia-suicide Severity Rating Scale (C-SSRS) at Week 4 Suicidal Behavior	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

SHP465

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=43 participants at risk Participant received placebo matched to SHP465 capsule orally once daily for 4 weeks.	SHP465 n=45 participants at risk Participants received 6.25 milligram (mg) of SHP465 capsule orally once daily for 4 weeks.
Nervous system disorders Headache	7.0% 3/43 • Number of events 4 • From start of study drug administration up to follow-up (Week 5) Safety analysis was analysed for the safety population (88 participants) and not for the enrolled population as in participant flow (89 participants).	4.4% 2/45 • Number of events 2 • From start of study drug administration up to follow-up (Week 5) Safety analysis was analysed for the safety population (88 participants) and not for the enrolled population as in participant flow (89 participants).

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER