title: The Efficacy and Safety of Evekeo, Racemic Amphetamine Sulfate, for Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms: A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled Crossover Laboratory Classroom Study.
abstract: OBJECTIVE
  The study goal was to determine the efficacy and safety of an optimal dose of Evekeo, racemic amphetamine sulfate, 1:1 d-amphetamine and l-amphetamine (R-AMPH), compared to placebo in treating children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting.
  
  
  METHODS
  A total of 107 children ages 6-12 years were enrolled in this multicenter, dose-optimized, randomized, double-blind, placebo-controlled crossover study. After 8 weeks of open-label dose optimization, 97 subjects were randomized to 2 weeks of double-blind treatment in the sequence of R-AMPH followed by placebo (n=47) or placebo followed by R-AMPH (n=50). Efficacy measures included the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) administered predose and at 0.75, 2, 4, 6, 8, and 10 hours postdose on 2 laboratory classroom days. Safety assessments included physical examination, chemistry, hematology, vital signs, and treatment-emergent adverse events (TEAEs).
  
  
  RESULTS
  Compared to placebo, a single daily dose of R-AMPH significantly improved SKAMP-Combined scores (p<0.0001) at each time point tested throughout the laboratory classroom days, with effect onset 45 minutes postdose and extending through 10 hours. R-AMPH significantly improved PERMP number of problems attempted and correct (p<0.0001) throughout the laboratory classroom days. During the twice-daily dose-optimization open-label phase, improvements were observed with R-AMPH in scores of the ADHD-Rating Scale IV and Clinical Global Impressions Severity and Improvement Scales. TEAEs and changes in vital signs associated with R-AMPH were generally mild and not unexpected. The most common TEAEs in the open-label phase were decreased appetite (27.6%), upper abdominal pain (14.3%), irritability (14.3%), and headache (13.3%).
  
  
  CONCLUSIONS
  Compared to placebo, R-AMPH was effective in treating children aged 6-12 years with ADHD, beginning at 45 minutes and continuing through 10 hours postdose, and was well tolerated.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01986062. https://clinicaltrials.gov/ct2/show/NCT01986062.
authors.affiliation: 1 Center for Psychiatry and Behavioral Medicine , Las Vegas, Nevada.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Childress
authors.affiliation: 2 Baylor College of Medicine , Houston, Texas.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brams
authors.affiliation: 3 University of Florida and Florida Clinical Research Center , Bradenton, Florida.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cutler
authors.affiliation: 4 Department of Psychiatry and Behavioral Science, Duke University , Durham, North Carolina.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kollins
authors.affiliation: 5 Florida Clinical Research Center , LLC, Maitland, Florida.
authors.forename: Jo
authors.initials: J
authors.lastname: Northcutt
authors.affiliation: 6 Miami Research Associates , South Miami, Florida.
authors.forename: Americo
authors.initials: A
authors.lastname: Padilla
authors.affiliation: 7 Westex Clinical Investigations , Lubbock, Texas.
authors.forename: John M
authors.initials: JM
authors.lastname: Turnbow
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; 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; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D013237:Stereoisomerism; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D000661:Amphetamine; D003913:Dextroamphetamine