Randomized, double-blind, placebo-controlled, crossover study of the effects of
lisdexamfetamine dimesylate and mixed amphetamine salts on cognition throughout
the day in adults with attention-deficit/hyperactivity disorder.
Author(s): Martin PT(1), Corcoran M, Zhang P, Katic A.
Affiliation(s): Author information:
(1)Shire Development LLC, 725 Chesterbrook Blvd, Wayne, PA, 19087-5637, USA,
pmartin@shire.com.
Publication date & source: 2014, Clin Drug Investig. , 34(2):147-57
BACKGROUND: Understanding 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.
OBJECTIVE: This 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).
METHODS: This 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.
RESULTS: This 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.
CONCLUSION: In 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.
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