A randomized crossover study to assess the pharmacokinetics of a novel amphetamine extended-release orally disintegrating tablet in healthy adults. Issue 7 (2nd October 2016) - Stark, Jeffrey G.
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 (Cmax ), time to maximum plasma concentration (Tmax ), elimination half-life (T1/2 ), area under the concentration-time curve from time zero to last quantifiable concentration (AUClast ), from time zero to infinity (AUCinf ), 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 Cmax, AUC5-last, AUClast, and AUCinf were within 80%–125% for both d -and l -amphetamine. The 90% CIs for AUC0-5 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 Cmax and approximately a 2-hour delay in Tmax . 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.