Low-impact ampakine CX717 exhibits promising therapeutic profile in adults with ADHD - A phase 2A clinical trial.

CX717, a low-impact ampakine, is a positive allosteric modulator of AMPA-glutamate receptors. This clinical study evaluated CX717 for the treatment of ADHD symptomology in a randomized, double-blind, placebo-controlled, multi-center, 2-period crossover with two doses of CX717 (200 or 800 mg BID). Each treatment period lasted 3 weeks with a 2-week washout. Subjects met DSM-IV criteria for adult ADHD and had moderate to severe symptoms. The primary efficacy measure was the change from baseline on the ADHD Rating Scale (ADHD-RS) with prompts. 68 male subjects, aged 18-50 years old were randomized. After accounting for early study dropouts, 51 subjects (75 %) returned for efficacy assessments and completed both treatment periods (intent-to-treat population). The primary analysis (paired t-test) showed a trend toward improvement in the 800 mg BID treatment group (p = .151) with a trend observed as early as week 1 (p = .148). A secondary repeated measures analysis at endpoint demonstrated that CX717 800 mg BID demonstrated superior efficacy compared to placebo on the total ADHD-RS (p = .002) and on both the inattentive (p = .027) and hyperactivity (p = .017) subscales. 200 mg BID did not significantly alter the above measures. Treatment with CX717 was well tolerated and did not significantly change cardiovascular and other safety parameters at either dose, nor did it produce hyperactivity. Sleep disturbance and headache were the most frequently reported adverse events. This study demonstrates that CX717 800 mg BID may be safely assessed in a larger cohort of adults with ADHD and provides evidence of the therapeutic utility of ampakines in ADHD treatment.