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Efficacy and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: sex and age effects and effect size across the day.

ABSTRACT: BACKGROUND:Efficacy and safety profiles by sex and age (6-9 vs 10-12 years) and magnitude and duration of effect by effect size overall and across the day of lisdexamfetamine dimesylate (LDX) vs placebo were assessed. METHODS:This study enrolled children (6-12 years) with attention-deficit/hyperactivity disorder (ADHD) in an open-label dose optimization with LDX (30-70 mg/d) followed by a randomized, double-blind, placebo-controlled, 2-way crossover phase. Post hoc analyses assessed interaction between sex or age and treatment and assessed effect sizes for Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) and Permanent Product Measure of Performance (PERMP) scales and ADHD Rating Scale IV measures. No corrections for multiple testing were applied on time points and subgroup statistical comparisons. RESULTS:129 participants enrolled; 117 randomized. Both sexes showed improvement on all assessments at postdose time points; females showed less impairment than males for SKAMP and PERMP scores in treatment and placebo groups at nearly all times. Both age groups improved on all assessments at postdose time points. Children 10-12 years had less impairment in SKAMP ratings than those 6-9 years. Treatment-by-sex interactions were observed at time points for SKAMP-D, SKAMP total, and PERMP scores; no consistent pattern across scales or time points was observed. LDX demonstrated significant improvement vs placebo, by effect size, on SKAMP-D from 1.5-13 hours postdose. The overall LS mean (SE) SKAMP-D effect size was -1.73 (0.18). In the dose-optimization phase, common (?2%) treatment-emergent adverse events (TEAEs) in males were upper abdominal pain, headache, affect lability, initial insomnia, and insomnia; in females were nausea and decreased weight. During the crossover phase for those taking LDX, higher incidence (?2% greater) was observed in males for upper abdominal pain and insomnia and in females for nausea and headache. Overall incidence of TEAEs in age groups was similar. CONCLUSION:Apparent differences in impairment level between sex and age groups were noted. However, these results support the efficacy of LDX from 1.5 hours to 13 hours postdose in boys and girls with medium to large effect sizes across the day with some variability in TEAE incidence by sex. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov Identifier: NCT00500149.

SUBMITTER: Wigal SB

PROVIDER: S-EPMC3022598 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Efficacy and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: sex and age effects and effect size across the day.

Wigal Sharon B SB Kollins Scott H SH Childress Ann C AC Adeyi Ben B

Child and adolescent psychiatry and mental health 20101214

<h4>Background</h4>Efficacy and safety profiles by sex and age (6-9 vs 10-12 years) and magnitude and duration of effect by effect size overall and across the day of lisdexamfetamine dimesylate (LDX) vs placebo were assessed.<h4>Methods</h4>This study enrolled children (6-12 years) with attention-deficit/hyperactivity disorder (ADHD) in an open-label dose optimization with LDX (30-70 mg/d) followed by a randomized, double-blind, placebo-controlled, 2-way crossover phase. Post hoc analyses assess ...[more]

PMID: 21156071

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Project description:ObjectiveTo evaluate the efficacy of lisdexamfetamine dimesylate in adults with attention deficit hyperactivity disorder symptom subtypes who exhibit predominantly inattention, hyperactivity/ impulsivity, or combined symptom clusters.Design/setting/participantsThis is a post-hoc analysis from a multicenter, one-year, open-label lisdexamfetamine dimesylate study in adults with attention deficit hyperactivity disorder previously completing two weeks or more in a four-week, randomized, placebo-controlled lisdexamfetamine dimesylate study, using Attention Deficit Hyperactivity Disorder Rating Scale IV symptom ratings as an attention deficit hyperactivity disorder subtype proxy (N=349).MeasurementsAttention Deficit Hyperactivity Disorder Rating Scale IV was measured at baseline of prior study and throughout the open-label study. Proxy subtypes were based on item scores of 2 (moderate) or 3 (severe), representing endorsement of at least six of nine symptoms on respective subscales; predominantly combined type endorsed at least six of nine symptoms on each subscale. Overall safety evaluations included treatment-emergent adverse events.ResultsAt baseline, 93 of 345 participants exhibited predominantly inattention, 13 predominantly hyperactivity/ impulsivity, 236 combined symptom clusters, and three were unassigned. For the three subgroups, respectively, mean (standard deviation) Attention Deficit Hyperactivity Disorder Rating Scale IV total scores at baseline were 34.5 (4.02), 33.8 (3.27), and 43.6 (5.24); change from baseline to endpoint scores were -19.3 (9.48), -24.0 (7.22), and -27.3 (11.78). Mean (standard deviation) end-of-study lisdexamfetamine dimesylate dose was 57.7 (14.75), 53.1 (16.01), and 56.9 (14.94)mg/day, respectively.Treatment-emergent adverse events (>5%) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), irritability (11.2%), anxiety (8.3%), nasopharyngitis (7.4%), sinusitis (6.6%), decreased weight (6.0%), back pain (5.4%), and muscle spasms (5.2%).ConclusionsLisdexamfetamine dimesylate was effective in participants with predominantly inattention, hyperactivity/ impulsivity, and combined attention deficit hyperactivity disorder symptom clusters. Groups exhibiting specific predominant subtype symptoms did not differ in clinical response to lisdexamfetamine dimesylate.

Project description: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.

Project description:BackgroundLisdexamfetamine dimesylate (LDX) is indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children 6 to 12 years of age and in adults. In a previous laboratory school study, LDX demonstrated efficacy 2 hours postdose with duration of efficacy through 12 hours. The current study further characterizes the time course of effect of LDX.MethodsChildren aged 6 to 12 years with ADHD were enrolled in a laboratory school study. The multicenter study consisted of open-label, dose-optimization of LDX (30, 50, 70 mg/d, 4 weeks) followed by a randomized, placebo-controlled, 2-way crossover phase (1 week each). Efficacy measures included the SKAMP (deportment [primary] and attention [secondary]) and PERMP (attempted/correct) scales (secondary) measured at predose and at 1.5, 2.5, 5, 7.5, 10, 12, and 13 hours postdose. Safety measures included treatment-emergent adverse events (AEs), physical examination, vital signs, and ECGs.ResultsA total of 117 subjects were randomized and 111 completed the study. Compared with placebo, LDX demonstrated significantly greater efficacy at each postdose time point (1.5 hours to 13.0 hours), as measured by SKAMP deportment and attention scales and PERMP (P < .005). The most common treatment-emergent AEs during dose optimization were decreased appetite (47%), insomnia (27%), headache (17%), irritability (16%), upper abdominal pain (16%), and affect lability (10%), which were less frequent in the crossover phase (6%, 4%, 5%, 1%, 2%, and 0% respectively).ConclusionIn school-aged children (6 to 12 years) with ADHD, efficacy of LDX was maintained from the first time point (1.5 hours) up to the last time point assessed (13.0 hours). LDX was generally well tolerated, resulting in typical stimulant AEs.Trial registrationOfficial Title: A Phase IIIb, Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Dose-Optimization, Cross-Over, Analog Classroom Study to Assess the Time of Onset of Vyvanse (Lisdexamfetamine Dimesylate) in Pediatric Subjects Aged 6-12 With Attention-Deficit/Hyperactivity Disorder. ClinicalTrials.gov Identifier: NCT00500149 http://clinicaltrials.gov/ct2/show/NCT00500149.

Project description:BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. Stimulants (methylphenidate [MPH] and amphetamine) are considered first-line ADHD pharmacotherapy. MPH is a catecholamine reuptake inhibitor, whereas amphetamines have additional presynaptic activity. Although MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many still fail to respond optimally to either. After administration, the prodrug stimulant lisdexamfetamine dimesylate (LDX) is converted to l-lysine and therapeutically active d-amphetamine in the blood. The objective of this study was to evaluate the clinical efficacy of LDX in children with ADHD who remained symptomatic (ie, nonremitters; ADHD Rating Scale IV [ADHD-RS-IV] total score > 18) on MPH therapy prior to enrollment in a 4-week placebo-controlled LDX trial, compared with the overall population.MethodsIn this post hoc analysis of data from a multicenter, randomized, double-blind, forced-dose titration study, we evaluated the clinical efficacy of LDX in children aged 6-12 years with and without prior MPH treatment at screening. ADHD symptoms were assessed using the ADHD-RS-IV scale, Conners' Parent Rating Scale-Revised short form (CPRS-R), and Clinical Global Impressions-Improvement scale, at screening, baseline, and endpoint. ADHD-RS-IV total and CPRS-R ADHD Index scores were summarized as mean (SD). Clinical response for the subgroup analysis was defined as a ≥ 30% reduction from baseline in ADHD-RS-IV score and a CGI-I score of 1 or 2. Dunnett test was used to compare change from baseline in all groups. Number needed to treat to achieve one clinical responder or one symptomatic remitter was calculated as the reciprocal of the difference in their proportions on active treatment and placebo at endpoint.ResultsOf 290 randomized participants enrolled, 28 received MPH therapy at screening, of which 26 remained symptomatic (ADHD-RS-IV > 18). ADHD-RS-IV total scores, changes from baseline, clinical responsiveness, and rates of symptomatic remission in this subgroup were comparable to the overall population. The safety and tolerability profiles for LDX were comparable to other stimulants currently available.ConclusionIn this analysis, children with significant clinical ADHD symptoms despite MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study population.Trial registrationClinicalTrials.gov: NCT00556296.

Dataset Information

Efficacy and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: sex and age effects and effect size across the day.

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Efficacy and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: sex and age effects and effect size across the day.

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