title: A randomized crossover study to assess the pharmacokinetics of a novel amphetamine extended-release orally disintegrating tablet in healthy adults.
abstract: OBJECTIVE
  In this pharmacokinetic (PK) study in healthy adults, we sought to: (1) compare the PK properties of a novel amphetamine extended-release orally disintegrating tablet formulation (Adzenys XR-ODT™ [AMP XR-ODT]) to a reference extended-release mixed amphetamine salts (MAS ER) formulation and (2) assess the effect of food on AMP XR-ODT.
  
  
  METHODS
  Forty-two adults were enrolled in a single-dose, open-label, 3-period, 3-treatment, randomized crossover study and received an 18.8-mg dose of AMP XR-ODT (fasted or fed) or equivalent dose (30 mg) of MAS ER (fasted). Plasma samples were analyzed for d-and l-amphetamine. Maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), elimination half-life (T1/2), area under the concentration-time curve from time zero to last quantifiable concentration (AUClast), from time zero to infinity (AUCinf), relevant partial AUCs, and weight-normalized clearance (CL/F/kg) were assessed. The PK parameters were compared across treatments using an ANOVA. Safety was also assessed.
  
  
  RESULTS
  A total of 39 adults completed this study. The geometric mean ratios (90% confidence interval [CI]) for AMP XR-ODT/MAS ER Cmax, AUC5-last, AUClast, and AUCinf were within 80%-125% for both d-and l-amphetamine. The 90% CIs for AUC0-5 were slightly below the 80%-125% range. When AMP XR-ODT was administered with food, there was a slight decrease in the d-and l-amphetamine Cmax and approximately a 2-hour delay in Tmax. The most common adverse events reported (>5% of participants) were dry mouth, palpitations, nausea, dizziness, headache, anxiety, and nasal congestion.
  
  
  CONCLUSIONS
  AMP XR-ODT displayed a PK profile similar to MAS ER, and no clinically relevant food effect was observed.
authors.affiliation: a Early Phase Services Division, Worldwide Clinical Trials , Austin , TX , USA.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Stark
authors.affiliation: b Regulatory Affairs, Neos Therapeutics, Inc. , Grand Prairie , TX , USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Engelking
authors.affiliation: c Research and Development, Neos Therapeutics, Inc. , Grand Prairie , TX , USA.
authors.forename: Russ
authors.initials: R
authors.lastname: McMahen
authors.affiliation: d Clinical Affairs, Neos Therapeutics, Inc. , Grand Prairie , TX , USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Sikes
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000661:Amphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004304:Dosage Forms; D004339:Drug Compounding / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000209:etiology; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency
chemical_list: D000697:Central Nervous System Stimulants; D004304:Dosage Forms; D000661:Amphetamine
keywords: ADHD treatment; Amphetamine extended-release orally disintegrating tablet; bioequivalence; food effect; pharmacokinetics