A Long-Term, Open-Label Safety and Tolerability Study of Lisdexamfetamine Dimesylate in Children Aged 4-5 Years with Attention-Deficit/Hyperactivity Disorder

Ann C Childress, Eric Lloyd, Steven A Johnson Jr, Lhanoo Gunawardhana, Valerie Arnold, Ann C Childress, Eric Lloyd, Steven A Johnson Jr, Lhanoo Gunawardhana, Valerie Arnold

Abstract

Objective: To evaluate the long-term safety and tolerability of lisdexamfetamine dimesylate (LDX) in preschool-aged children (4-5 years of age inclusive) diagnosed with attention-deficit/hyperactivity disorder (ADHD). Methods: This phase 3 open-label study (ClinicalTrials.gov registry: NCT02466386) enrolled children aged 4-5 years meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for a primary ADHD diagnosis and having baseline ADHD Rating Scale-IV Preschool version total scores (ADHD-RS-IV-PS-TS) ≥24 for girls or ≥28 for boys and baseline Clinical Global Impressions-Severity scores ≥4. Participants were directly enrolled or enrolled after completing one of two antecedent short-term LDX studies. Over 52 weeks of treatment, participants received once-daily dose-optimized LDX (5-30 mg). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital sign changes. Clinical outcomes included ADHD-RS-IV-PS-TS changes from baseline. Results: Among 113 participants in the safety set, optimized LDX dose was 5, 10, 15, 20, and 30 mg in 1 (0.9%), 12 (10.6%), 21 (18.6%), 26 (23.0%), and 53 (46.9%) participants, respectively. Of the safety set, 69 participants (61.1%) completed the study. TEAEs were reported in 76.1% of participants; no serious TEAEs were reported. Only one type of TEAE was reported in >10% of participants (decreased appetite, 15.9%). Mean ± standard deviation (SD) changes in vital signs and body weight from baseline to week 52/or early termination (ET; n = 101) were 1.9 ± 7.73 mmHg for systolic blood pressure, 3.1 ± 7.58 mmHg for diastolic blood pressure, 4.7 ± 11.00 bpm for pulse, and 0.6 ± 1.38 kg for body weight. Over the course of the study, mean ± SD change in ADHD-RS-IV-PS-TS from baseline to week 52/ET was -24.2 ± 13.34 (n = 87). Conclusions: In this long-term 52-week study of children aged 4-5 years with ADHD, dose-optimized LDX (5-30 mg) was well tolerated and associated with reductions from baseline in ADHD symptoms.

Keywords: attention-deficit/hyperactivity disorder; efficacy; lisdexamfetamine dimesylate; preschool-aged children; safety; tolerability.

Figures

FIG. 1.
FIG. 1.
Study design. *All participants underwent the dose optimization period except those who enrolled following the phase 2 antecedent study, which included a similar dose optimization phase. Week 52/ET, data from protocol-defined last treatment study visit or early termination visit.
FIG. 2.
FIG. 2.
Participant disposition. Ph 2 (NCT02402166) and Ph 3 (NCT03260205) are antecedent studies. LAR, legally authorized representative; LDX, lisdexamfetamine dimesylate; PBO, placebo; Ph, phase.
FIG. 3.
FIG. 3.
Mean change from BL in ADHD-RS-IV-PS-TS score by optimized LDX dose (safety analysis set). *Data from protocol-defined last treatment study visit or early termination visit. ADHD, attention-deficit/hyperactivity disorder; ADHD-RS-IV-PS-TS, ADHD Rating Scale-IV, Preschool version total scores; BL, baseline; LDX, lisdexamfetamine dimesylate.
FIG. 4.
FIG. 4.
Proportion of participants with improved Clinical Global Impressions score by optimized LDX dose (safety analysis set). *Data from protocol-defined last treatment study visit or early termination visit. BL, baseline; CGI-I, Clinical Global Impressions–Improvement; LDX, lisdexamfetamine dimesylate.

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