title: European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder.
abstract: This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6-17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ≥ 28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 (95% confidence interval [CI]: -21.5 to -15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 (95% CI: -15.9 to -10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70-86), 14% (8-21), and 61% (51-70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD.
authors: Division of Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. Electronic address: d.r.coghill@dundee.ac.uk.
authors: David
authors: D
authors: Coghill
authors: Tobias
authors: T
authors: Banaschewski
authors: Michel
authors: M
authors: Lecendreux
authors: Cesar
authors: C
authors: Soutullo
authors: Mats
authors: M
authors: Johnson
authors: Alessandro
authors: A
authors: Zuddas
authors: Colleen
authors: C
authors: Anderson
authors: Richard
authors: R
authors: Civil
authors: Nicholas
authors: N
authors: Higgins
authors: Andrew
authors: A
authors: Lyne
authors: Liza
authors: L
authors: Squires
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects*; D001069:Appetite Regulation / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002652:Child Behavior / Q000187:drug effects*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004351:Drug Resistance; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007175:Impulsive Behavior / Q000209:etiology / Q000517:prevention & control*; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D010352:Patient Dropouts; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine
keywords: Adolescent; Attention deficit disorder with hyperactivity; Central nervous system stimulants; Child; Lisdexamfetamine dimesylate; Prodrugs