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

Attention Deficit Hyperactivity Disorder (ADHD) Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind, Multicenter, Placebo-controlled, Fixed-Dose, Efficacy, and Safety Study of SHP465 in Children Aged 6-12 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03325881
• Other study ID #: SHP465-309
• Status: Completed
• Phase: Phase 3
• Start date: December 9, 2017
• Est. completion date: June 7, 2018

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of SHP465 at 6.25 mg in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children aged 6-12 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: June 7, 2018
• Est. primary completion date: June 7, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 12 Years

Eligibility

Inclusion Criteria:

• Participant is male or female aged 6-12 years inclusive at the time of consent.

• Participant's parent or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent (as applicable) by the participant.

• Participant must meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD (any subtype).

• Participant who is a female and of child-bearing potential must not be pregnant and agree to comply with any applicable contraceptive requirements.

• Participant has an ADHD-RS-5 Child, Home Version Total Score of greater than or equal to (>=) 28 and Clinical Global Impression - Severity of Illness (CGI-S) score >=4 at baseline (Visit 2). Participant is currently not on ADHD therapy, or is not completely satisfied with their current ADHD therapy.

Exclusion Criteria:

• Participant is required or anticipated to take medications that have central nervous system effects or affect performance. Stable use of bronchodilator inhalers is not exclusionary.

• Participant has a concurrent chronic or acute illness, disability, or other condition that might confound the results of safety assessments conducted in the study or that might increase risk to the participant.

• Participant has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.

• Participant has failed to fully respond, based on investigator judgment, to an adequate course of amphetamine therapy.

• Participant has a known family history of sudden cardiac death or ventricular arrhythmia.

• Participant has a blood pressure measurement >=95th percentile for age, sex, and height at screening (Visit 1) and/or baseline (Visit 2).

• Participant has a height less than or equal to (<=) 5th percentile for age and sex at screening (Visit 1) or baseline (Visit 2).

• Participant has a weight <=5th percentile for age and sex at screening (Visit 1) or baseline (Visit 2).

• Participant has a 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.

• Participant has a history of seizures (other than infantile febrile seizures).

• Participant is taking any medication that is excluded per the protocol.

• Participant had any clinically significant ECG or clinical laboratory abnormalities at the screening (Visit 1) or baseline visit (Visit 2).

• Participant has current abnormal thyroid function, defined as abnormal thyroid-stimulating hormone and thyroxine at the screening or baseline visit. Treatment with a stable dose of thyroid medication for at least 3 months is permitted.

• Participant has a current, controlled (requiring medication or therapy) or uncontrolled, comorbid psychiatric disorder.

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

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder (ADHD)
• Hyperkinesis

Intervention

Drug:
• SHP465
SHP465 capsule 6.25 mg orally once daily for 4 weeks
• Placebo
Placebo matching to SHP465 capsule orally once daily for 4 weeks

Locations

Country	Name	City	State
United States	Advanced Research Center	Anaheim	California
United States	GA Psychiatric Services, LLC.	Atlanta	Georgia
United States	Kentucky Pediatric/Adult Research	Bardstown	Kentucky
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Neurobehavioral Medicine Group	Bloomfield Hills	Michigan
United States	Buford Family Practice	Buford	Georgia
United States	Coastal Pediatric Associates	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Ohio Pediatric Research Association	Dayton	Ohio
United States	Care Research Center	Doral	Florida
United States	Harmonex Neuroscience Research	Dothan	Alabama
United States	Triangle Neuropsychiatry	Durham	North Carolina
United States	El Campo Clinical Trials	El Campo	Texas
United States	Pedia Research, LLC	Evansville	Indiana
United States	Power MD Clinical Research Institute	Hialeah	Florida
United States	Houston Clinical Trials, LLC	Houston	Texas
United States	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida
United States	Children's Clinic	League City	Texas
United States	PEWMD, PA, ARCSM, PLLC, PRP, Inc.	Little Rock	Arkansas
United States	Advanced Clinical Research Inc.	Meridian	Idaho
United States	Acevedo Medical Group	Miami	Florida
United States	Pharmacology Research, LLC	Miami	Florida
United States	Coastal Pediatric Associates	Mount Pleasant	South Carolina
United States	Conventions Psychiatry and Counseling	Naperville	Illinois
United States	Access Clinical Trials, Inc.	Nashville	Tennessee
United States	One Health Research Clinic, Inc.	Norcross	Georgia
United States	Scientific Clinical Research Inc.	North Miami	Florida
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Clinical Associates of Orlando, Llc	Orlando	Florida
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	Psychiatric Associates	Overland Park	Kansas
United States	Pedia Research, LLC	Owensboro	Kentucky
United States	VA South Psychiatric & Family Services	Petersburg	Virginia
United States	Mid-Columbia Research	Richland	Washington
United States	Riverside Medical Clinic	Riverside	California
United States	Neuroscientific Insights	Rockville	Maryland
United States	Peninsula Research Associates - CRN	Rolling Hills	California
United States	St Charles Psychiatric Associates	Saint Charles	Missouri
United States	University of Texas	San Antonio	Texas
United States	Institute for Behavioral Medicine	Smyrna	Georgia
United States	Family Practice Center of Wadsworth, Inc.	Wadsworth	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) Total Score at Week 4	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.	Baseline, Week 4
Secondary	Clinical Global Impression of Improvement (CGI-I) at 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.	Week 4
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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.	From start of study drug administration up to follow-up (Week 5)
Secondary	Number of Participants With Clinically Significant Change in Vital Signs Were Reported as Adverse Event (AE)	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.	From start of study drug administration up to follow-up (Week 5)
Secondary	Number of Participants With Clinically Significant Change in Clinical Laboratory Test Results Assessed by the Investigator	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.	From start of study drug administration up to follow-up (Week 5)
Secondary	Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Assessed by the Investigator	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.	From start of study drug administration up to follow-up (Week 5)
Secondary	Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4	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.	Baseline, Week 4
Secondary	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	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.	Baseline, Week 4
Secondary	Change From Baseline in Length of Time Sleeping Per Night Assessed by PSQ at Week 4	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.	Baseline, Week 4
Secondary	Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Week 4	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.	Week 4
Secondary	Number of Participants With a Positive Response in Columbia-suicide Severity Rating Scale (C-SSRS) at Week 4	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.	Week 4