Clinical trial NCT02466386: Safety and Tolerability Study of SPD489 in Preschool Children Aged 4-5 Years, Diagnosed With Attention-deficit/Hyperactivity Disorder
Official title: A Phase 3, Open-label, Multicenter, 12-Month Safety and Tolerability Study of SPD489 in Preschool Children Aged 4-5 Years Diagnosed With Attention-deficit / Hyperactivity Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-06-09
Enrollment: 113
Sex: ALL
Minimum age (years): 4
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the long-term safety of SPD489 administered as a daily morning dose (5, 10, 15, 20, and 30 mg/day) in preschool children diagnosed with Attention-deficit/Hyperactivity Disorder (ADHD).

Detailed description: This study is a long-term, open-label study where participants who participated in an antecedent SPD489 study (SPD489-211 \[NCT02402166\] or SPD489-347 \[NCT03260205\]) or through direct enrollment. Participants entering into this study will be classified as either a roll-over participants or a direct-enrolled participants.

Eligibility criteria: Inclusion Criteria:

1. Participant is male or female aged 4-5 years inclusive at the time of consent from antecedent studies SPD489-211 or SPD489-347 or at the time of consent if directly enrolled.
2. Before completing any study-related procedures, 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 indicating that the participant is aware of the investigational nature of the study. The participant's parent(s) or LAR should understand that the required procedures and restrictions are being conducted in accordance with the International Council of Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (1996), any updates or revisions, and applicable federal or local regulations.
3. 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. Specifically, the parent/LAR should be available at approximately 7:00AM (+2 hours) to dispense the dose of investigational product for the duration of the study.
4. Roll-over participant from antecedent SPD489-347 study:

   a. Participant completed the antecedent study (SPD489-347)
5. Direct enrolled participants must meet antecedent study inclusion criteria, as listed below

   1. Participant must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) criteria for a primary diagnosis of ADHD (any subtype) based on a detailed psychiatric evaluation conducted by a sponsor-approved clinician
   2. Participant has an attention-deficit/hyperactivity disorder rating scale- IV (ADHD-RS-IV) Preschool Version total score at the Baseline Visit (Visit 0) of greater than equals to (\>=) 28 for boys and \>= 24 for girls.
   3. Participant has a Clinical Global Impressions - Severity of Illness (CGI-S) score \>=4 at the Baseline Visit (Visit 0).
   4. Participant has a Peabody Picture Vocabulary Test, Fourth Edition standard score of \>=70 at the Screening Visit (Visit -1).
   5. Participant has undergone an adequate course of non-pharmacological treatment based on investigator judgment or the participant has a severe enough condition to consider enrollment without undergoing prior non-pharmacological treatment, based on investigator judgment.
   6. Participant has, in the opinion of the investigator, participated in a structured group activity (eg, preschool, sports, Sunday school) so as to assess symptoms and impairment in a setting outside the home.
   7. Participant has lived with the same parent(s) or guardian for \>=6 months.

Exclusion Criteria:

1. Participant was terminated from an antecedent SPD489 study for non-compliance and/or experienced a serious adverse event (SAE) or adverse event (AE) resulting in termination.
2. Participant is required to or anticipates the need to take medications that have central nervous system effects or affect performance, such as, but not limited to, sedating antihistamines and decongestant sympathomimetics, or monoamine oxidase inhibitors. Stable use of bronchodilator inhalers is not exclusionary.
3. Participant has a concurrent chronic or acute illness (such as, but not limited to, severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments conducted in the study or that might increase risk to the participant. Similarly, the participant will be excluded if he or she has any additional condition(s) that, in the investigator's opinion, would prohibit the participant from completing the study or would not be in the best interest of the participant. The additional condition(s) would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol. Mild, stable asthma is not exclusionary.
4. Participant has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
5. Participant has a known family history of sudden cardiac death or ventricular arrhythmia.
6. Participant has a blood pressure measurement \>= 95th percentile for age, sex, and height at the screening visit (Visit -1) or the baseline visit (Visit 0) or a history of moderate or severe hypertension.
7. 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 placing them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
8. Participant is taking any medication that is excluded per the protocol.
9. Participant had any clinically significant electrocardiogram (ECG) or clinical laboratory abnormalities at the Screening Visit (Visit -1) or baseline visit (Visit 0), based on investigator judgment.
10. Participant has a history of hyperthyroidism, or current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4) at the Screening Visit (Visit-1) or Visit 0. Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
11. Participant has taken another investigational product or has taken part in a clinical study within 30 days prior to the Screening Visit (Visit -1).
12. Participant is well-controlled on his/her current ADHD medication with acceptable tolerability.
13. Participant has glaucoma.
14. Participant has failed to fully respond, based on investigator judgment, to an adequate course of amphetamine therapy.
15. Participant has a current, controlled (requiring medication or therapy) or uncontrolled, comorbid psychiatric disorder including but not limited to any of the below co-morbid Axis I disorders and Axis II disorders:

    1. post-traumatic stress disorder (PTSD) or adjustment disorder
    2. bipolar illness, psychosis, or family history of these disorders
    3. pervasive developmental disorder
    4. obsessive-compulsive disorder (OCD)
    5. psychosis/schizophrenia
    6. participant has a serious tic disorder, or a family history of Tourette's disorder
    7. 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. Participants with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the investigator
    8. a history of physical, sexual, or emotional abuse
    9. 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.
16. Participant has initiated behavioral therapy within 1 month of the baseline visit (Visit 0). Participant may not initiate behavioral therapy during the study.
17. Participant has a height \<=5th percentile for age and sex at the screening visit (Visit -1).
18. Participant has a weight \<=5th percentile for age and sex at the screening visit (Visit -1).
19. Participant lives with anyone who currently abuses stimulants or cocaine.
20. Participant has a history of seizures (other than infantile febrile seizures).

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to follow-up (Week 53)
measure: Change From Baseline in Sleep Patterns Assessed by Children's Sleep Habits Questionnaire (CSHQ) at Week 52/ Early Termination (ET)
timeFrame: Week 52/ET
measure: Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters at Week 52/ Early Termination (ET)
timeFrame: Week 52/ET
measure: Number of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS) at Week 52/ Early Termination (ET)
timeFrame: Week 52/ET
measure: Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values at Week 52/ Early Termination (ET)
timeFrame: Week 52/ET
measure: Number of Participants With Potentially Clinically Significant Changes in Vital Signs at Week 52/ Early Termination (ET)
timeFrame: Week 52/ET
measure: Number of Participants With Shift From Baseline in Body Mass Index (BMI) Percentiles at Week 52/Early Termination (ET)
timeFrame: Week 52/ET
Secondary outcomes:
measure: Clinical Global Impressions Global Improvement (CGI-I) at Week 52/ Early Termination (ET)
timeFrame: Week 52/ET
measure: Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 52/ Early Termination (ET)
timeFrame: Week 52/ET
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: 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: Newport Beach
country: United States
facility: AVIDA
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: University of California
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: 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: Las Vegas
country: United States
facility: Center For Psychiatry and Behavioral Medicine In
state: Nevada
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: Durham
country: United States
facility: Duke Child and Family Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
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
state: Washington
Study officials:
affiliation: Shire
name: Shire Physician
role: STUDY_DIRECTOR
References:
citation: Childress AC, Lloyd E, Johnson SA Jr, Gunawardhana L, Arnold V. A Long-Term, Open-Label Safety and Tolerability Study of Lisdexamfetamine Dimesylate in Children Aged 4-5 Years with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2022 Mar;32(2):98-106. doi: 10.1089/cap.2021.0138. Epub 2022 Mar 8.