A randomized pilot study of the efficacy and safety of ABT-089, a novel α4β2 neuronal nicotinic receptor agonist, in adults with attention-deficit/hyperactivity disorder.
OBJECTIVE
ABT-089, an α4β2 neuronal nicotinic receptor partial agonist (generic name pozanicline), has demonstrated efficacy in adults with attention-deficit/hyperactivity disorder (ADHD) at doses of 40 mg once daily and 40 mg twice daily. The purpose of this exploratory pilot study was to obtain initial safety, tolerability, and efficacy data for an ABT-089 80-mg once-daily regimen to inform a decision of whether to include an 80-mg once-daily dose regimen in subsequent, definitive (phase 3) efficacy studies.


METHODS
This phase 2, randomized, double-blind, parallel-group, placebo-controlled pilot study was conducted at 12 sites from March to August 2008. A screening/washout period of up to 4 weeks was followed by an 8-week double-blind treatment period. Eligible subjects met DSM-IV-TR criteria for ADHD and were randomized in a 1:1:1 ratio to ABT-089 40 mg once daily, ABT-089 80 mg once daily, or placebo. The primary efficacy variable was reduction from baseline to the final evaluation in the investigator-rated Conners' Adult ADHD Rating Scale for each active treatment group versus placebo. Safety assessments and pharmacokinetic sampling were also conducted.


RESULTS
A total of 160 subjects were randomized, with 137 (86%) completing the trial. No statistically significant treatment effects were observed with either ABT-089 dose for any efficacy measures. The most commonly reported adverse events in the active treatment groups were nasopharyngitis (6.6%), upper respiratory tract infection (6.6%), and somnolence (5.7%). The incidence of adverse events did not differ significantly between active groups and placebo. There were no clinically significant laboratory, electrocardiogram, or physical examination findings.


CONCLUSIONS
ABT-089 was generally well tolerated at doses up to 80 mg. Because ABT-089 is a weak partial neuronal nicotinic receptor agonist, the results may not predict the potential efficacy for other, more potent neuronal nicotinic receptor agonists.


BACKGROUND
ClinicalTrials.gov identifier: NCT00640185.
Abbott, Abbott Park, IL 60064, USA. Earle.Bain@abbott.com
Earle E
EE
Bain
George
G
Apostol
R Bart
RB
Sangal
Weining Z
WZ
Robieson
Dawnelle L
DL
McNeill
Walid M
WM
Abi-Saab
Mario D
MD
Saltarelli
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D054333:Drug Partial Agonism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000009:adverse effects* / Q000627:therapeutic use*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011725:Pyridines / Q000009:adverse effects* / Q000819:agonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000009:adverse effects* / Q000819:agonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000187:drug effects
D018722:Nicotinic Agonists; D011725:Pyridines; D011759:Pyrrolidines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C108326:pozanicline