Clinical trial NCT03260205: Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-deficit/Hyperactivity Disorder (ADHD)
Official title: A Phase 3, Randomized, Double-blind, Multicenter, Parallel-group, Placebo-controlled, Fixed-Dose Safety and Efficacy Study of SPD489 Compared With Placebo in Preschool Children Aged 4-5 Years With Attention-deficit/Hyperactivity Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Keywords: SPD489
Lisdexamfetamine dimesylate
ADHD
hyperactivity
Neurobehavioral disorder
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-08-24
Enrollment: 199
Sex: ALL
Minimum age (years): 4
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if an investigational treatment is effective in improving the total score on the ADHD-RS-IV Preschool Version in children 4-5 years old diagnosed with ADHD.


Eligibility criteria: Inclusion Criteria:

* Participant is a male or female aged 4-5 years inclusive at the time of consent
* Participant's parent(s) or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) by the participant before completing any study related procedures.
* Participant and parent(s)/LAR are willing and able to comply with all of the testing and requirements defined in the protocol, including oversight of morning dosing.
* Participant must meet DSM-IV-TR criteria for a primary diagnosis of ADHD (any sub-type).
* Participant has an ADHD-RS-IV Preschool Version Total Score at the baseline visit (Visit 0) greater than or equal to 28 for boys, and greater than or equal to 24 for girls.
* Participant has a Clinical Global Impressions - Severity of Illness (CGI-S) score greater than or equal to 4 at the baseline visit (Visit 0).
* Participant has a Peabody Picture Vocabulary Test standard score of greater than or equal to 70 at the screening visit (Visit -1).
* Participant has undergone an adequate course of non-pharmacological treatment or has a severe enough condition to consider enrollment without undergoing prior non-pharmacological treatment.
* Participant has participated in a structured group activity (e.g, preschool, sports, Sunday school) so as to assess symptoms and impairment in a setting outside the home.
* Participant has lived with the same parent(s) or guardian for greater than or equal to 6 months.

Exclusion Criteria:

* Participant is required to or anticipates the need to take any prohibited medications or medications that have central nervous system (CNS) effects or have an effect on performance. Stable use of bronchodilator inhalers is not exclusionary.
* Participant has taken another investigational product or has taken part in a clinical study within 30 days prior to the screening visit (Visit -1).
* Participant is well-controlled on his/her current ADHD medication with acceptable tolerability.
* Participant has a concurrent chronic or acute illness, disability, or other condition that might confound the results of safety assessments or may increase risk to the participant..
* Participant has glaucoma.
* Participant has failed to fully respond to an adequate course of amphetamine therapy.
* Participant has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
* Participant has a known family history of sudden cardiac death or ventricular arrhythmia.
* Participant has a blood pressure measurement greater than or equal to 95th percentile for age, sex, and height at the screening visit (Visit -1) or the baseline visit (Visit 0) or history of moderate or severe hypertension.
* Participant has a known history of symptomatic cardiovascular disease, unexplained syncope, exertional chest pain,advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems.
* Participant has any clinically significant clinical laboratory abnormalities at the screening visit (Visit -1) or electrocardiogram (ECG) at screening visit (Visit-1) or baseline visit (Visit 0) based on investigator judgment.
* Participant has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4) at the screening visit (Visit -1). 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, co-morbid psychiatric disorder including but not limited to any of the below co-morbid Axis I disorders and Axis II disorders:

  i. post-traumatic stress disorder or adjustment disorder ii. bipolar illness, psychosis, or a family history of these disorders iii. pervasive developmental disorder iv. obsessive-compulsive disorder (OCD) v. psychosis/schizophrenia vi. a serious tic disorder, or a family history of Tourette's disorder vii. 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 is currently demonstrating active suicidal ideation.

viii. a history of physical, sexual, or emotional abuse ix. any other disorder or agitated state that in the opinion of the investigator, contraindicates SPD489 or lisdexamfetamine dimesylate treatment or confound efficacy or safety assessments.

* Participant has initiated behavioral therapy within 1 month of the baseline visit (Visit 0). Participant may not initiate behavioral therapy during the study.
* Participant has a height less than equal to (\<=) 5th percentile for age and sex at the screening visit (Visit -1).
* Participant has a weight \<= 5th percentile for age and sex at the screening visit (Visit -1).
* Participant lives with anyone who currently abuses stimulants or cocaine.
* Participant has a history of seizures (other than infantile febrile seizures).
* Participant is taking any medication that is excluded per the protocol.

Primary outcomes:
measure: Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6
timeFrame: Baseline, Week 6
Secondary outcomes:
measure: Clinical Global Impressions Global Improvement (CGI-I) at Week 6
timeFrame: Week 6
measure: Dose Response Relationship for Change From Baseline in ADHD-RS-IV Preschool Version Total Score in Preschool Children at Week 6
timeFrame: Baseline, Week 6
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to follow-up (Week 7)
measure: Number of Participants With Potentially Clinically Significant Changes in Vital Signs
timeFrame: Week 6
measure: Change From Baseline in Height at Week 6
timeFrame: Baseline, Week 6
measure: Change From Baseline in Body Weight at Week 6
timeFrame: Baseline, Week 6
measure: Change From Baseline in Body Mass Index (BMI) at Week 6
timeFrame: Baseline, Week 6
measure: Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values
timeFrame: Week 6
measure: Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters
timeFrame: Week 6
measure: Children's Sleep Habits Questionnaire (CSHQ) at Week 6
timeFrame: Week 6
measure: Number of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Week 6
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Harmonex, Inc
state: Alabama
city: Little Rock
country: United States
facility: Preferred Research Partners, Inc
state: Arkansas
city: Colton
country: United States
facility: CMB Clinical Trials
state: California
city: Imperial
country: United States
facility: Sun Valley Research Center
state: California
city: Long Beach
country: United States
facility: Alliance for Wellness d/b/a Alliance for Research
state: California
city: Panorama City
country: United States
facility: Asclepes Research
state: California
city: San Diego
country: United States
facility: Psychiatric Centers at San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Dept of Psychiatry
state: California
city: Wildomar
country: United States
facility: Elite Clinical Trials, Inc
state: California
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: Orlando
country: United States
facility: APG Research, LLC
state: Florida
city: Saint Petersburg
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida Department Of Psychiatry
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta LLC
state: Georgia
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: Sterling Heights
country: United States
facility: Clinical Neurophysiology Services
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Lincoln
country: United States
facility: Premier Psychiatric Reseach Institute, LLC
state: Nebraska
city: Neptune
country: United States
facility: Jersey Shore University Medical Center (JSUMC)
state: New Jersey
city: New York
country: United States
facility: Manhattan Behavioral Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Fairfield
country: United States
facility: Pediatric Associates of Fairfield, Inc
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Clinical Research Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Paradigm Research Professionals
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Gresham
country: United States
facility: Cyn3rgy Research Center
state: Oregon
city: Barnwell
country: United States
facility: Rainbow Research Inc
state: South Carolina
city: Charleston
country: United States
facility: Carolina Clinical Trials, Inc.
state: South Carolina
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research
state: South Carolina
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Tennessee
city: Austin
country: United States
facility: BioBehavioral Research of Austin
state: Texas
city: Houston
country: United States
facility: Bayou City Research Limited
state: Texas
city: Houston
country: United States
facility: BI Research Center
state: Texas
city: Houston
country: United States
facility: Red Oak Psychiatry Associates
state: Texas
city: San Antonio
country: United States
facility: Road Runner Research
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of the Woodlands
state: Texas
city: Clinton
country: United States
facility: Ericksen Research and Development
state: Utah
city: Petersburg
country: United States
facility: Clinical Research Partners, LLC
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: Seattle Childrens Hospital, Pearl Clinic
state: Washington
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Childress AC, Lloyd E, Jacobsen L, Gunawardhana L, Johnson SA Jr, Findling RL. Efficacy and Safety of Lisdexamfetamine in Preschool Children With Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2022 Dec;61(12):1423-1434. doi: 10.1016/j.jaac.2022.03.034. Epub 2022 May 13.