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

Phase 3
Completed
Conditions
Attention Deficit Hyperactivity Disorder (ADHD)
Interventions
Drug: Placebo
Registration Number
NCT03325881
Lead Sponsor
Shire
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
89
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipant will receive placebo matching to SHP465 capsule orally once daily for 4 weeks.
SHP465SHP465Participants will be randomized to receive SHP465 capsule 6.25 milligram (mg) orally once daily for 4 weeks.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) Total Score at Week 4Baseline, 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.

Secondary Outcome Measures
NameTimeMethod
Clinical Global Impression of Improvement (CGI-I) at Week 4Week 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.

Number of Participants With Quality of Sleep Assessed by Post Sleep Questionnaire (PSQ) at Baseline and Week 4Baseline, 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.

Change From Baseline in Length of Time Awake Per Night and Length of Time to Fall Asleep Per Night Assessed by PSQ at Week 4Baseline, 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.

Change From Baseline in Length of Time Sleeping Per Night Assessed by PSQ at Week 4Baseline, 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.

Total Sleep Disturbance Score of Children's Sleep Habits Questionnaire (CSHQ ) at Week 4Week 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.

Number of Participants With Clinically Significant Change in Vital Signs Were Reported as Adverse Event (AE)From start of study drug administration up to follow-up (Week 5)

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.

Number of Participants With Clinically Significant Change in Clinical Laboratory Test Results Assessed by the InvestigatorFrom start of study drug administration up to follow-up (Week 5)

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.

Number of Participants With a Positive Response in Columbia-suicide Severity Rating Scale (C-SSRS) at Week 4Week 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.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)From start of study drug administration up to follow-up (Week 5)

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.

Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Assessed by the InvestigatorFrom start of study drug administration up to follow-up (Week 5)

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.

Trial Locations

Locations (38)

Pedia Research, LLC

🇺🇸

Owensboro, Kentucky, United States

Acevedo Medical Group

🇺🇸

Miami, Florida, United States

Advanced Research Center

🇺🇸

Anaheim, California, United States

Harmonex Neuroscience Research

🇺🇸

Dothan, Alabama, United States

Riverside Medical Clinic

🇺🇸

Riverside, California, United States

Care Research Center

🇺🇸

Doral, Florida, United States

Peninsula Research Associates - CRN

🇺🇸

Rolling Hills, California, United States

Power MD Clinical Research Institute

🇺🇸

Hialeah, Florida, United States

Pharmacology Research, LLC

🇺🇸

Miami, Florida, United States

Scientific Clinical Research Inc.

🇺🇸

North Miami, Florida, United States

One Health Research Clinic, Inc.

🇺🇸

Norcross, Georgia, United States

Buford Family Practice

🇺🇸

Buford, Georgia, United States

Institute for Behavioral Medicine

🇺🇸

Smyrna, Georgia, United States

GA Psychiatric Services, LLC.

🇺🇸

Atlanta, Georgia, United States

Conventions Psychiatry and Counseling

🇺🇸

Naperville, Illinois, United States

Kentucky Pediatric/Adult Research

🇺🇸

Bardstown, Kentucky, United States

Neuroscientific Insights

🇺🇸

Rockville, Maryland, United States

Neurobehavioral Medicine Group

🇺🇸

Bloomfield Hills, Michigan, United States

St Charles Psychiatric Associates

🇺🇸

Saint Charles, Missouri, United States

Triangle Neuropsychiatry

🇺🇸

Durham, North Carolina, United States

Family Practice Center of Wadsworth, Inc.

🇺🇸

Wadsworth, Ohio, United States

Ohio Pediatric Research Association

🇺🇸

Dayton, Ohio, United States

Coastal Pediatric Associates

🇺🇸

Mount Pleasant, South Carolina, United States

El Campo Clinical Trials

🇺🇸

El Campo, Texas, United States

Houston Clinical Trials, LLC

🇺🇸

Houston, Texas, United States

Children's Clinic

🇺🇸

League City, Texas, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

University of Texas

🇺🇸

San Antonio, Texas, United States

Northwest Clinical Research Center

🇺🇸

Bellevue, Washington, United States

VA South Psychiatric & Family Services

🇺🇸

Petersburg, Virginia, United States

Mid-Columbia Research

🇺🇸

Richland, Washington, United States

PEWMD, PA, ARCSM, PLLC, PRP, Inc.

🇺🇸

Little Rock, Arkansas, United States

Advanced Clinical Research Inc.

🇺🇸

Meridian, Idaho, United States

Psychiatric Associates

🇺🇸

Overland Park, Kansas, United States

Access Clinical Trials, Inc.

🇺🇸

Nashville, Tennessee, United States

IPS Research Company

🇺🇸

Oklahoma City, Oklahoma, United States

Clinical Neuroscience Solutions, Inc.

🇺🇸

Orlando, Florida, United States

Clinical Associates of Orlando, Llc

🇺🇸

Orlando, Florida, United States

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