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

George Apostol, Walid Abi-Saab, Christopher J Kratochvil, Lenard A. Adler, Weining Z. Robieson, Laura M. Gault, Yili L. Pritchett, David Feifel, Michelle A. Collins, Mario D. Saltarelli

Research output: Contribution to journalArticle

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Abstract

Rationale: α 4β 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 4β 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.

Original languageEnglish (US)
Pages (from-to)715-725
Number of pages11
JournalPsychopharmacology
Volume219
Issue number3
DOIs
StatePublished - Feb 1 2012

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Nicotinic Receptors
Attention Deficit Disorder with Hyperactivity
Cross-Over Studies
Placebos
Safety
Nasopharyngitis
Research Personnel
Sleep Initiation and Maintenance Disorders
pozanicline
Least-Squares Analysis
Respiratory Tract Infections
Headache
Therapeutics

Keywords

  • ADHD
  • Attention
  • Nicotinic

ASJC Scopus subject areas

  • Pharmacology

Cite this

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

In: Psychopharmacology, Vol. 219, No. 3, 01.02.2012, p. 715-725.

Research output: Contribution to journalArticle

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. / Efficacy and safety of the novel α 4β 2 neuronal nicotinic receptor partial agonist ABT-089 in adults with attention-deficit/hyperactivity disorder : A randomized, double-blind, placebo-controlled crossover study. In: Psychopharmacology. 2012 ; Vol. 219, No. 3. pp. 715-725.
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abstract = "Rationale: α 4β 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 4β 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.",
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AU - Abi-Saab, Walid

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AU - Robieson, Weining Z.

AU - Gault, Laura M.

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