Efficacy and safety of the novel [α.sub.4][β.sub.2] neuronal nicotinic receptor partial agonist ABT-089 in adults with attention-deficit/ hyperactivity disorder: a randomized, double-blind, placebo-controlled crossover study

• Published in: Psychopharmacology Vol. 219; no. 3; p. 715
• Main Authors: Apostol, George, Abi-Saab, Walid, Kratochvil, Christopher J, Adler, Lenard A, Robieson, Weining Z, Gault, Laura M, Pritchett, Yili L, Feifel, David, Collins, Michelle A, Saltarelli, Mario D
• Format: Journal Article
• Language: English
• Published: Springer 01.02.2012
• Subjects: Adults; Analysis; Attention-deficit hyperactivity disorder; Medical research; Medicine, Experimental; Neurons; Pharmaceutical industry; United States; United Kingdom; Switzerland
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-011-2393-2

Rationale [α.sub.4][β.sub.2] Neuronal nicotinic receptors (NNRs) are implicated in the pathophysiology of attention-deficit/ hyperactivity disorder (ADHD). Objectives This study examined the efficacy and safety of the [α.sub.4][β.sub.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 x 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 ([greater than or equal to] 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. Keywords Nicotinic * ADHD * Attention