M. Shram,1 K. Schoedel,1 N. Chen,2 D. Kelsh,3 C. O'Brien,4 B. Robertson,4 T. Hsu4; 1Altreos Research Partners Inc., Toronto, ON, Canada, 2Alstat, Toronto, ON, Canada, 3Vince & Associates Clinical Research, Overland Park, KS, 4Neurovance, Inc., Cambridge, MA
BACKGROUND: Centanafadine (EB-1020) is a triple reuptake inhibitor (TRI) under development for the treatment of attention-deficit hyperactivity disorder (ADHD). TRIs have been considered for use in ADHD because they inhibit reuptake of norepinephrine and dopamine (DA), neurotransmitters known to mediate symptoms of inattention, impulsivity and hyperactivity in ADHD. Since TRIs increase DA in the nucleus accumbens, potential for drug liking and recreational abuse should be considered. This exploratory clinical study assessed centanafadine’s subjective abuse potential in recreational stimulant users.
METHODS: A double-blind, randomized five-way crossover study with single oral doses of centanafadine (400 and 800 mg), d-amphetamine (d-AMP 40 mg), lisdexamfetamine (LDX 150 mg), and placebo was conducted in 36 recreational stimulant users. Subjective effects (eg, bipolar visual analog scale [VAS] of Drug Liking) and safety measures were assessed up to 24 h after each dose (48 h washout between doses).
RESULTS: Maximum Drug Liking VAS (DL Emax) was significantly higher for d-AMP and LDX vs. placebo, confirming study validity. DL Emax for centanafadine was higher compared to placebo and not different from d-AMP and LDX; however, minimum DL (Emin) for centanafadine was significantly lower compared to placebo, d-AMP and LDX, indicating significant disliking, and occurred within 0.5 hours post-dose. Centanafadine was associated with a higher incidence of nausea (eg, 56.3% at 800 mg) and emesis (59.4%) vs. d-AMP, LDX and placebo (0-3%).
CONCLUSION: Centanafadine was associated with early onset of negative effects (eg, disliking and emesis), suggesting a lower abuse potential compared to d-AMP and LDX.