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Study Results Suggest Lower Abuse Potential for Centanafadine Compared With Stimulants Used for Adult ADHD

Treatment combines measurable reward with negative effects

Positive results have been reported from a human abuse liability (HAL) study of sustained-release centanafadine, a triple reuptake inhibitor, in recreational stimulant users. The drug is being developed for the treatment of adults with attention-deficit hyperactivity disorder (ADHD) and has shown favorable efficacy with good tolerability in a phase IIa study.

The new findings were presented at the 53rd annual meeting of the American College of Neuropsychopharmacology, held in Phoenix, Arizona.

Centanafadine works by modulating the activity of norepinephrine, dopamine, and serotonin, three neurotransmitters known to be relevant in patients with ADHD. In the HAL study, immediate-release centanafadine demonstrated a reduced abuse potential compared with the schedule II stimulants d-amphetamine and lisdexamfetamine (Vyvanse, Shire).

Treatment with high doses of immediate-release centanafadine resulted in a markedly different profile than that of the comparators, with most subjects experiencing the acute onset of adverse effects, including nausea, vomiting, and dysphoria. Almost 2 hours after the administration of centanafadine, the test subjects reported “liking” at about two-thirds of the magnitude of amphetamines, a finding that may have indicated dopamine activity. However, unlike amphetamines, which provided an immediate positive experience, the subjects receiving centanafadine experienced negative effects before reaching that point. This early adverse profile of centanafadine is inherent to the norepinephrine and serotonin pharmacology of the molecule, and is believed likely to deter abuse if the sustained-release formulation is used, according to the product’s developer (Neurovance, Inc.).

The HAL study was a five-arm crossover trial designed to evaluate the abuse liability potential of immediate-release centanafadine in subjects known to use recreational stimulants. Single doses of 400 mg or 800 mg were tested alongside the schedule II comparators d-amphetamine and lisdexamfetamine (Vyvanse), along with placebo. The findings showed that immediate-release centanafadine, at a dose sufficient to elicit a measurable reward, would also result in negative effects. For example, subjects said they would significantly prefer to take d-amphetamine compared with centanafadine 800 mg.

Adult ADHD is a serious medical condition that results in disabling levels of inattention, distraction, and impulsive actions. Approximately 10 million American adults are estimated to have ADHD, but only one in ten receives a diagnosis and treatment. Adult ADHD is often associated with serious psychiatric co-morbidities, including depression, anxiety, and substance abuse. According to recent data from IMS Health, the 2013 U.S. ADHD prescription market for adults is now larger than that for children, with 30 million and 29 million total prescriptions written, respectively.

Source: Neurovance, Inc.; December 11, 2014.

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