title: Safety and efficacy of ABT-089 in pediatric attention-deficit/hyperactivity disorder: results from two randomized placebo-controlled clinical trials.
abstract: OBJECTIVE
  To assess the safety and efficacy of ABT-089, a novel α(4)β(2) neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted. Study 1 (n = 274) assessed six treatment groups over 8 weeks: 4 once-daily (QD) ABT-089 doses (0.085-0.700 mg/kg), QD atomoxetine, and placebo. Study 2 (n = 119) assessed three treatment groups over 6 weeks: 2 QD ABT-089 doses (0.7 mg/kg, 1.4 mg/kg) and placebo. The primary efficacy variable was the investigator-administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV: Home Version (ADHD-RS-IV [HV]) Total Score. Safety was assessed by adverse event (AE) monitoring, laboratory tests, vital signs, physical examinations, and electrocardiogram measures.
  
  
  RESULTS
  There was no statistically significant difference between ABT-089 and placebo in mean change from baseline to final evaluation of ADHD-RS-IV (HV) Total Score or other outcome measures at any dose in either study. In Study 1, atomoxetine showed statistically significant improvement for the primary and most secondary endpoints. ABT-089 was generally safe and well tolerated, with no statistically significant difference between any ABT-089 dose and placebo in the overall incidence of any specific AE, and no clinically significant changes in other safety measures.
  
  
  CONCLUSIONS
  ABT-089 did not show efficacy on the primary efficacy variable, the ADHD-RS-IV (HV) Total Score, or other measures of ADHD symptomatology in children with ADHD, and had a safety profile similar to placebo. These results contrast with published reports of efficacy of nicotinic modulators in adults with ADHD.
authors.affiliation: Massachusetts General Hospital, Pediatric Psychopharmacology Unit, 55 Fruit Street, Boston, MA 02114, USA. twilens@partners.org
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Wilens
authors.forename: Laura M
authors.initials: LM
authors.lastname: Gault
authors.forename: Ann
authors.initials: A
authors.lastname: Childress
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kratochvil
authors.forename: Lindsey
authors.initials: L
authors.lastname: Bensman
authors.forename: Coleen M
authors.initials: CM
authors.lastname: Hall
authors.forename: Evelyn
authors.initials: E
authors.lastname: Olson
authors.forename: Weining Z
authors.initials: WZ
authors.lastname: Robieson
authors.forename: Tushar S
authors.initials: TS
authors.lastname: Garimella
authors.forename: Walid M
authors.initials: WM
authors.lastname: Abi-Saab
authors.forename: George
authors.initials: G
authors.lastname: Apostol
authors.forename: Mario D
authors.initials: MD
authors.lastname: Saltarelli
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000009:adverse effects; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects; D011569:Psychiatric Status Rating Scales; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011759:Pyrrolidines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018722:Nicotinic Agonists; D011437:Propylamines; D011725:Pyridines; D011759:Pyrrolidines; D000069445:Atomoxetine Hydrochloride; C108326:pozanicline