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).

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 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.

Trial registration: ClinicalTrials.gov NCT00528697 NCT00640419.

Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Subject disposition and flow through studies Note: aSubjects may have reported more than one reason for premature discontinuation, but are counted only once in the total

Figure 2

Mean change from baseline to each study visit on (A) Attention-deficit/hyperactivity disorder Rating Scale-IV: Home Version Total score and (B) Clinical Global Impression- Attention-deficit/hyperactivity disorder-Severity Scale score (Intent-to-treat dataset) Note: One-sided P-values from mixed model repeated-measures analysis with factors for treatment group, site, visit, and treatment group-by-visit interaction, with continuous fixed covariates of baseline score and baseline score-by-visit interaction presented. ADHD-RS-IV (HV) = Attention-deficit/hyperactivity disorder Rating Scale-IV: Home Version; CGI-ADHD-S = Clinical Global Impression-Attention-deficit/hyperactivity disorder-Severity scale; SE = standard error.