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Physician perception of clinical improvement in children with attention-deficit/hyperactivity disorder: a post hoc comparison of lisdexamfetamine dimesylate and mixed amphetamine salts extended release in a crossover analog classroom study.

ABSTRACT: OBJECTIVE:To assess effects of lisdexamfetamine dimesylate (LDX) and mixed amphetamine salts extended release (MAS XR) on symptom improvement in children with attention-deficit/hyperactivity disorder (ADHD). METHODS:Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover analog-classroom environment was conducted. The primary efficacy outcome was the deportment subscale of the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP-D) rating scale. The secondary efficacy outcome was the investigator-rated Clinical Global Impressions-Improvement (CGI-I), a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), which assesses improvement over time from baseline. McNemar test was used to compare participants' responses to LDX and MAS XR on CGI-I scores dichotomized into 1 (very much improved) vs all other response scores (2 to 7) in a 2 × 2 table. RESULTS:Fifty-two children (aged 6 to 12 years) were enrolled, titrated, and randomized; 50 completed the study. Investigators rated 74% of LDX participants as either very much improved or much improved on the CGI-I scale relative to 72% of MAS XR participants and 18% of placebo participants. Of the 50 children who completed the study, 32% of LDX participants were very much improved vs 16% of MAS XR, and 2% of placebo participants relative to baseline. McNemar test indicated that 10 participants were very much improved with LDX, but not MAS XR; 2 participants were very much improved with MAS XR, but not LDX; 6 participants were very much improved with both, while 32 were not very much improved with either. Analysis showed that LDX had a significantly higher number of children with a very much improved score on the CGI-I than MAS XR (P = 0.0386). CONCLUSION:Treatment of children with LDX resulted in a higher number of participants with a very much improved score on the CGI-I than treatment with MAS XR or placebo.

SUBMITTER: Lopez FA

PROVIDER: S-EPMC3101887 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Physician perception of clinical improvement in children with attention-deficit/hyperactivity disorder: a post hoc comparison of lisdexamfetamine dimesylate and mixed amphetamine salts extended release in a crossover analog classroom study.

López Frank A FA Scheckner Brian B Childress Ann C AC

Neuropsychiatric disease and treatment 20110506

<h4>Objective</h4>To assess effects of lisdexamfetamine dimesylate (LDX) and mixed amphetamine salts extended release (MAS XR) on symptom improvement in children with attention-deficit/hyperactivity disorder (ADHD).<h4>Methods</h4>Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover analog-classroom environment was conducted. The primary efficacy outcome was the deportment subscale of the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP-D) rating scale. The secondary ...[more]

PMID: 21654872

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Project description:BackgroundUnderstanding the nature and time course of the pharmacodynamic effects of attention-deficit/hyperactivity disorder (ADHD) medications is useful. The Cognitive Drug Research Computerized Battery of Tests (CDR-CBT) is a 20-min battery of ten standardized, validated neuropsychometric tasks.ObjectiveThis pilot study examined the sensitivity and responsiveness of the CDR-CBT for assessing cognitive function in adults with ADHD prior to and up to 16 h postdose during treatment with lisdexamfetamine dimesylate (LDX) or mixed amphetamine salts immediate release (MAS-IR; various generics available).MethodsThis was a double-blind three-period crossover study. Participants received LDX 50 mg/day, MAS-IR 20 mg/day, and placebo (~7 a.m.) for 7 days each in randomized order. CDR-CBT was administered on day 1 of period 1 and day 7 of each period at scheduled times between -0.5 (predose) and 16 h postdose. Composite power of attention (PoA) score (sum of simple reaction time, choice reaction time, and digit vigilance speed) was the primary outcome measure. The Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S) was administered at baseline and on day 1 of period 1, and days 6 and 7 of each treatment period. Tertiary outcomes included CDR-CBT composite continuity of attention scores, its component task scores, cognitive reaction time, and response variability scores. No inferential statistical comparisons were conducted. Safety assessments included adverse events (AEs) and vital signs.ResultsThis analysis included 18 participants (mean age 30.8 years); one withdrew because of AEs. Mean pretreatment PoA scores were 1175.9-1361.2 ms, scores commensurate with a normative age of >40 years. Maximum reductions in PoA scores with LDX and MAS-IR occurred at 5 h postdose at day 7 (least squares mean difference [95% CI] of -150.0 [-235.41 to -64.50] and -79.8 [-165.72 to 6.21] ms vs. placebo, respectively). CAARS-S:S scores were unchanged with LDX and MAS-IR (vs. placebo) at all postdose timepoints. Tertiary attention-related CDR-CBT outcomes were sensitive to LDX and MAS-IR (vs. placebo). Treatment-emergent AEs and vital signs were consistent with previous studies in adult ADHD.ConclusionIn adults with ADHD, PoA scores indicated impaired attention at baseline and response to treatment with LDX and MAS-IR (vs. placebo), demonstrating value for measuring the time course of pharmacologic treatment effects.

Project description:BackgroundThis open-label, crossover study examined lisdexamfetamine dimesylate (LDX) and D-amphetamine pharmacokinetics in healthy adults after administration of an intact LDX capsule or after the capsule was emptied into orange juice or yogurt and the contents consumed.MethodsHealthy adult volunteers (N = 30) were administered a 70-mg LDX capsule or the contents of a 70-mg capsule mixed with yogurt or orange juice using a 3-way crossover design. Blood samples were collected serially for up to 96 hours after dose. Pharmacokinetic endpoints included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from zero to infinity (AUC0-∞) or to last assessment (AUClast). Relative LDX and D-amphetamine bioavailabilities from the contents of a 70-mg LDX capsule mixed with orange juice or yogurt were compared with those from the intact LDX capsule using bioequivalence-testing procedures.ResultsGeometric least squares mean ratios (90% confidence intervals [CIs]) for D-amphetamine (active moiety) were within the prespecified bioequivalence range (0.80-1.25) when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.971 (0.945, 0.998); AUC0-∞: 0.986 (0.955, 1.019); AUClast: 0.970 (0.937, 1.004)] or yogurt [Cmax: 0.970 (0.944, 0.997); AUC0-∞: 0.945 (0.915, 0.976); AUClast: 0.944 (0.912, 0.977)]. Geometric least squares mean ratios (90% CIs) for LDX (inactive prodrug) were below the accepted range when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.641 (0.582, 0.707); AUC0-∞: 0.716 (0.647, 0.792); AUClast: 0.708 (0.655, 0.766)]; the lower 90% CI for Cmax [0.828 (0.752, 0.912)] was below the accepted range when the contents of a 70-mg LDX capsule were mixed with yogurt.ConclusionsRelative bioavailability of D-amphetamine (the active moiety) did not differ across administrations, which suggests that emptying an LDX capsule into orange juice or yogurt and consuming it is an alternative to intact capsules.

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.

Project description:OBJECTIVE:To 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/PARTICIPANTS:This 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). MEASUREMENTS:Attention 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. RESULTS:At 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%). CONCLUSIONS:Lisdexamfetamine 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.

Dataset Information

Physician perception of clinical improvement in children with attention-deficit/hyperactivity disorder: a post hoc comparison of lisdexamfetamine dimesylate and mixed amphetamine salts extended release in a crossover analog classroom study.

Publications

Physician perception of clinical improvement in children with attention-deficit/hyperactivity disorder: a post hoc comparison of lisdexamfetamine dimesylate and mixed amphetamine salts extended release in a crossover analog classroom study.

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