EPA-0682 – Investigator-Rated Symptomatological Outcomes in a Phase 4 Study of Lisdexamfetamine Dimesylate in Adults with Attention-Deficit/Hyperactivity Disorder and Impaired Executive Function

Abstract

Introduction:

Symptoms of attention-deficit/hyperactivity disorder (ADHD) appear in childhood, but are recognised as often persistent into adulthood. Impairments in day-to-day functioning associated with ADHD in adults include deficiency in executive function.

Objectives:

Evaluate the effect of lisdexamfetamine dimesylate (LDX) on ADHD symptoms in adults with ADHD and executive function deficit.

Methods:

This phase 4, randomized, double-blind study enrolled adults (aged 18–55) with baseline ADHD Rating Scale IV with Adult Prompts (ADHD-RSIV- Adult) total score ≥28 and baseline Global Executive Composite T-score ≥65 on the Behaviour Rating Inventory of Executive Function–Adult Version. Patients were randomized 1:1 to receive optimized doses of LDX (30, 50 or 70 mg/day) or placebo for up to 10 weeks. The change from baseline in the investigator-rated ADHD-RS-IV-Adult total score was a secondary efficacy outcome.

Results:

The full analysis set comprised 154 patients (LDX, n=79; placebo, n=75). At baseline, mean ADHD-RS-IV-Adult total score was 39.9 in both groups (standard deviation [SD]: LDX, 6.83; placebo, 7.37) and mean changes from baseline to week 10 or early termination were −21.4 (SD, 11.27) and −10.3 (12.70) in the LDX and placebo groups, respectively. Statistical analysis showed a significant difference (LDX minus placebo) in least-squares mean changes of −11.1 (95% confidence interval: −14.9, −7.3), with an effect size of 0.94 in favour of LDX (p<0.0001). Safety outcomes were consistent with previous studies and the known effects of stimulant treatment.

Conclusion:

Short-term treatment with LDX markedly reduced ADHD symptoms in adults with ADHD and impaired executive function.

Study funded by Shire.