Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose Study to Evaluate the Efficacy and Safety of the Amphetamine Extended-Release Tablet in Adults with Attention-Deficit/Hyperactivity Disorder

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by pervasive impairment in symptoms of inattention, hyperactivity, and impulsivity. Psychopharmacologic treatment is targeted at the management of symptoms of ADHD, and evidence exists that ADHD persists into adulthood. Clinical practice guidelines recommend a combination of behavior therapy and psychostimulant medication for the treatment of ADHD in children, adolescents, and adults. Psychostimulants are often prescribed for ADHD in adults, and amphetamine long has been considered a mainstay of treatment for this population. As adult patients seek relief from ADHD symptoms early in the workday and into the early evening hours, with fewer required doses, extended-release formulations with an early onset of efficacy and an extended duration of effect are considered very desirable. The amphetamine-extended release tablet (AMPH ER TAB) was developed to provide a portable, easy-to-use amphetamine tablet dosage option that can be chewed or swallowed whole. To evaluate the efficacy and safety of an Amphetamine Extended-Release Tablet (AMPH ER TAB) in adults with ADHD aged 18 to 60years. Methods: In a 5-week forced dose-titration phase, eligible subjects were randomized to either oral double-blind AMPH ER TAB 5mg starting dose or matching placebo, once daily in the morning beginning the day after the Baseline Visit. Subjects were titrated up (5mg increments) each week. Safety and efficacy assessments were done weekly. After Visit 3, subjects received 20mg for 14 (3) days before Visit 5 (V5). Subjects who could not tolerate study drugs discontinued. A Permanent Product Measure of Performance (PERMP) placement test was done at Screening or Baseline. At V5, efficacy assessments included the administration of serial PERMPs predose, 0.5, 1, 2, 4, 8, 10, 12, 13, and 14hours postdose. The primary efficacy endpoint was the mean PERMP-T score across postdose time points during the Visit 5 serial PERMPs. Safety was monitored by AEs assessed at each visit, C-SSRS, vital signs, weight, and assessment of sleep, appetite, mood, and psychotic AEs. The mean postdose PERMP-T score over all postdose time points at V5 was statistically significantly higher in the AMPH ER TAB group vs placebo (302.8 vs 279.6; P=.0043). Common adverse events were decreased appetite, insomnia, and dry mouth. The majority of TEAEs were mild to moderate in severity, and no SAEs were reported. The AMPH ER TAB demonstrated efficacy in the treatment of symptoms of ADHD in adults, with an anticipated safety profile. Tris Pharma, Inc.