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
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Attention Deficit Hyperactivity Disorder (ADHD)
- Sponsor
- Shire
- Enrollment
- 199
- Locations
- 48
- Primary Endpoint
- Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
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.
Arms & Interventions
Placebo
Participant will receive placebo matching to SPD489 (Lisdexamfetamine dimesylate) capsule for 6 weeks.
Intervention: Placebo
SPD489 (Lisdexamfetamine dimesylate)
Participants will be randomized to receive SPD489 capsule in a 5:5:5:5:6 ratio to SPD489 5, 10, 20, 30 milligram (mg) orally once daily for 6 weeks. Dosing will begin with the lowest strength of SPD489 (5 mg), and will be titrated until the randomly assigned fixed-dose is reached.
Intervention: SPD489 (Lisdexamfetamine dimesylate)
SPD489 (Lisdexamfetamine dimesylate)
Participants will be randomized to receive SPD489 capsule in a 5:5:5:5:6 ratio to SPD489 5, 10, 20, 30 milligram (mg) orally once daily for 6 weeks. Dosing will begin with the lowest strength of SPD489 (5 mg), and will be titrated until the randomly assigned fixed-dose is reached.
Intervention: SPD489
Outcomes
Primary Outcomes
Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6
Time Frame: Baseline, Week 6
ADHD-RS-IV Preschool Version was adapted from the ADHD Rating Scale-IV and provided examples appropriate for the developmental level of preschool children. The ADHD-RS-IV Preschool Version was an 18-item questionnaire that required the respondent to rate the frequency of occurrence of ADHD symptoms as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria. Each item was scored on a 4-point scale ranging from 0 (never or rarely) to 3 (very often) with total scores ranging from 0-54. The 18 items were grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17). Full analysis set (FAS) consisted of all participants in the safety analysis set who had at least 1 post-dose ADHD RS IV preschool version total score assessment.
Secondary Outcomes
- Clinical Global Impressions Global Improvement (CGI-I) at Week 6(Week 6)
- Dose Response Relationship for Change From Baseline in ADHD-RS-IV Preschool Version Total Score in Preschool Children at Week 6(Baseline, Week 6)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From start of study drug administration up to follow-up (Week 7))
- Number of Participants With Potentially Clinically Significant Changes in Vital Signs(Week 6)
- Change From Baseline in Height at Week 6(Baseline, Week 6)
- Change From Baseline in Body Weight at Week 6(Baseline, Week 6)
- Change From Baseline in Body Mass Index (BMI) at Week 6(Baseline, Week 6)
- Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values(Week 6)
- Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters(Week 6)
- Children's Sleep Habits Questionnaire (CSHQ) at Week 6(Week 6)
- Number of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS)(Up to Week 6)