A randomized crossover study to assess the pharmacokinetics of a novel amphetamine extended-release orally disintegrating tablet in healthy adults

ABSTRACT

Objectives: In this pharmacokinetic (PK) study in healthy adults, we sought to: (1) compare the PK properties of a novel amphetamine extended-release orally disintegrating tablet formulation (Adzenys XR-ODT™ [AMP XR-ODT]) to a reference extended-release mixed amphetamine salts (MAS ER) formulation and (2) assess the effect of food on AMP XR-ODT.

Methods: Forty-two adults were enrolled in a single-dose, open-label, 3-period, 3-treatment, randomized crossover study and received an 18.8-mg dose of AMP XR-ODT (fasted or fed) or equivalent dose (30 mg) of MAS ER (fasted). Plasma samples were analyzed for d-and l-amphetamine. Maximum plasma concentration (C_max), time to maximum plasma concentration (T_max), elimination half-life (T_1/2), area under the concentration-time curve from time zero to last quantifiable concentration (AUC_last), from time zero to infinity (AUC_inf), relevant partial AUCs, and weight-normalized clearance (CL/F/kg) were assessed. The PK parameters were compared across treatments using an ANOVA. Safety was also assessed.

Results: A total of 39 adults completed this study. The geometric mean ratios (90% confidence interval [CI]) for AMP XR-ODT/MAS ER C_max, AUC_5-last, AUC_last, and AUC_inf were within 80%–125% for both d-and l-amphetamine. The 90% CIs for AUC_0-5 were slightly below the 80%–125% range. When AMP XR-ODT was administered with food, there was a slight decrease in the d-and l-amphetamine C_max and approximately a 2-hour delay in T_max. The most common adverse events reported (>5% of participants) were dry mouth, palpitations, nausea, dizziness, headache, anxiety, and nasal congestion.

Conclusions: AMP XR-ODT displayed a PK profile similar to MAS ER, and no clinically relevant food effect was observed.

KEYWORDS:

• Amphetamine extended-release orally disintegrating tablet
• pharmacokinetics
• bioequivalence
• food effect
• ADHD treatment

Declaration of interest

Writing and editorial support was provided by Jennifer Tyson of AlphaBioCom, LLC, and funded by Neos Therapeutics, Inc. J Stark is an employee of Worldwide Clinical Trials. R McMahen is an employee of Neos Therapeutics with stock options. D Engelking is an employee of Neos Therapeutics with stock options. C Sikes is an employee of Neos Therapeutics with stock options in Neos Therapeutics and stock in Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This article was funded by Neos Therapeutics.