title: Efficacy and safety of the novel α₄β₂ neuronal nicotinic receptor partial agonist ABT-089 in adults with attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled crossover study.
abstract: BACKGROUND
  α(4)β(2) Neuronal nicotinic receptors (NNRs) are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD).
  
  
  OBJECTIVE
  This study examined the efficacy and safety of the α(4)β(2) NNR partial agonist ABT-089 versus placebo in adults with ADHD.
  
  
  METHODS
  In this multicenter, randomized, double-blind, placebo-controlled crossover study, subjects received placebo followed by ABT-089 (2 mg once daily [QD], 5 mg QD, 15 mg QD, 40 mg QD, or 40 mg twice daily [BID]), or vice versa, in a 2 × 2 crossover design. Each treatment period was 4 weeks, separated by a 2-week washout period. The primary efficacy endpoint was the Conners' Adult ADHD Rating Scale-Investigator Rated (CAARS:Inv) total score at the end of each treatment period. Secondary outcomes based on clinician- and self-rated efficacy scales were evaluated.
  
  
  RESULTS
  Of the 221 subjects enrolled, 171 met criteria for inclusion in the completers dataset for efficacy analyses. ABT-089 was superior to placebo on the CAARS:Inv total score at 40 mg QD and 40 mg BID (model-based least square mean difference from placebo: -4.33, P = 0.02; -3.02, P = 0.03, respectively). ABT-089 also demonstrated significant improvements on several secondary measures of efficacy. ABT-089 was generally safe and well tolerated. The most commonly reported adverse events (≥5%) for total ABT-089-treated subjects at rates higher than placebo were headache, upper respiratory tract infection, irritability, insomnia, and nasopharyngitis.
  
  
  CONCLUSIONS
  In this phase 2 crossover study, the NNR partial agonist ABT-089, at doses of 40 mg QD and 40 mg BID, was efficacious and generally well tolerated in treatment of adults with ADHD.
authors: Abbott, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
authors: George
authors: G
authors: Apostol
authors: Walid
authors: W
authors: Abi-Saab
authors: Christopher J
authors: CJ
authors: Kratochvil
authors: Lenard A
authors: LA
authors: Adler
authors: Weining Z
authors: WZ
authors: Robieson
authors: Laura M
authors: LM
authors: Gault
authors: Yili L
authors: YL
authors: Pritchett
authors: David
authors: D
authors: Feifel
authors: Michelle A
authors: MA
authors: Collins
authors: Mario D
authors: MD
authors: Saltarelli
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D054333:Drug Partial Agonism; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D018722:Nicotinic Agonists; D011725:Pyridines; D011759:Pyrrolidines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C108326:pozanicline