Safety and efficacy of ABT-089 in pediatric attention-deficit/hyperactivity disorder

Results from two randomized placebo-controlled clinical trials

Timothy E. Wilens, Laura M. Gault, Ann Childress, Christopher J Kratochvil, Lindsey Bensman, Coleen M. Hall, Evelyn Olson, Weining Z. Robieson, Tushar S. Garimella, Walid M. Abi-Saab, George Apostol, Mario D. Saltarelli

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Objective To assess the safety and efficacy of ABT-089, a novel α4β2 neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). Method 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 ScaleIV: 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. Clinical Trial Registry Information- M06-888 (Study 1): A Safety and Efficacy Study of ABT-089 in Children With Attention-Deficit/Hyperactivity Disorder (ADHD), URL: http://clinicaltrials.gov, unique identifier: NCT00528697. M10-345 (Study 2): Safety and Tolerability Study of ABT-089 in Children With Attention-Deficit/Hyperactivity Disorder (ADHD), URL: http://clinicaltrials.gov, unique identifier: NCT00640419.

Original languageEnglish (US)
Pages (from-to)73-84.e1
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume50
Issue number1
DOIs
StatePublished - Jan 1 2011

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Attention Deficit Disorder with Hyperactivity
Randomized Controlled Trials
Placebos
Pediatrics
Safety
pozanicline
Vital Signs
Nicotinic Receptors
Physical Examination
Registries
Electrocardiography
Research Personnel
Outcome Assessment (Health Care)
Clinical Trials
Incidence
Therapeutics

Keywords

  • ADHD
  • neuronal nicotinic receptor
  • pharmacologic treatment
  • α4β2

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health

Cite this

Safety and efficacy of ABT-089 in pediatric attention-deficit/hyperactivity disorder : Results from two randomized placebo-controlled clinical trials. / Wilens, Timothy E.; Gault, Laura M.; Childress, Ann; Kratochvil, Christopher J; Bensman, Lindsey; Hall, Coleen M.; Olson, Evelyn; Robieson, Weining Z.; Garimella, Tushar S.; Abi-Saab, Walid M.; Apostol, George; Saltarelli, Mario D.

In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 50, No. 1, 01.01.2011, p. 73-84.e1.

Research output: Contribution to journalArticle

Wilens, TE, Gault, LM, Childress, A, Kratochvil, CJ, Bensman, L, Hall, CM, Olson, E, Robieson, WZ, Garimella, TS, Abi-Saab, WM, Apostol, G & Saltarelli, MD 2011, 'Safety and efficacy of ABT-089 in pediatric attention-deficit/hyperactivity disorder: Results from two randomized placebo-controlled clinical trials', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 50, no. 1, pp. 73-84.e1. https://doi.org/10.1016/j.jaac.2010.10.001
Wilens, Timothy E. ; Gault, Laura M. ; Childress, Ann ; Kratochvil, Christopher J ; Bensman, Lindsey ; Hall, Coleen M. ; Olson, Evelyn ; Robieson, Weining Z. ; Garimella, Tushar S. ; Abi-Saab, Walid M. ; Apostol, George ; Saltarelli, Mario D. / Safety and efficacy of ABT-089 in pediatric attention-deficit/hyperactivity disorder : Results from two randomized placebo-controlled clinical trials. In: Journal of the American Academy of Child and Adolescent Psychiatry. 2011 ; Vol. 50, No. 1. pp. 73-84.e1.
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N2 - Objective To assess the safety and efficacy of ABT-089, a novel α4β2 neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). Method 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 ScaleIV: 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. Clinical Trial Registry Information- M06-888 (Study 1): A Safety and Efficacy Study of ABT-089 in Children With Attention-Deficit/Hyperactivity Disorder (ADHD), URL: http://clinicaltrials.gov, unique identifier: NCT00528697. M10-345 (Study 2): Safety and Tolerability Study of ABT-089 in Children With Attention-Deficit/Hyperactivity Disorder (ADHD), URL: http://clinicaltrials.gov, unique identifier: NCT00640419.

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