Single-Dose Pharmacokinetics of Amphetamine Extended-Release Tablet (AMPH ER TAB) Compared With Amphetamine Extended-Release Oral Suspension (AMPH EROS)

OBJECTIVES: Evaluate bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole/chewed and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB (contains a 3.2:1 ratio of d- to l-amphetamine).

METHODS: Healthy volunteers (18-55 yr) randomized to AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover design was used. Samples collected pre-dose and at time points to 60 h post-dose. D- and l-amphetamine measured, Cmax, AUCt, and AUC0∞ were calculated. Comparative bioavailability was determined when ratios were 80-125%. Safety was assessed.

RESULTS: 32 subjects completed. Ratios: AMPH ER TAB swallowed vs. AMPH EROS fasted: For d-amphetamine: AUC0-t: 100.68-108.08%, AUC0-∞:101.47-109.52%, Cmax: 98.10-103.17%. For l-amphetamine: AUC0-t: 100.31-108.57%, AUC0-∞:101.27-111.09%, Cmax: 98.2-103.37%. AMPH ER TAB chewed vs. AMPH EROS fasted: For d-amphetamine: AUC0-t: 99.23-106.62%, AUC0-∞: 99.58-107.59%, Cmax: 99.91-105.14%. For l-amphetamine: AUC0-t: 98.16-106.35%, AUC0-∞: 98.44-108.11%, Cmax: 99.53-104.75%. Food effect: AMPH ER TAB, chewed, fasted vs. fed: For d-amphetamine: AUC0-t: 92.57-99.49%, AUC0-∞: 91.12-98.48%, Cmax: 94.22-99.17%. For l-amphetamine: AUC0-t: 91.27-98.91%, AUC0-∞: 88.44-97.17%, Cmax: 94.52-99.50%). No serious AEs were reported, and the AE profiles were similar to other amphetamine formulations used in ADHD.

CONCLUSIONS: Bioavailability of AMPH ER TAB for both d- and l-amphetamine was comparable, swallowed whole or chewed, to an equivalent 20 mg dose of the reference product AMPH EROS, 2.5 mg/mL fasted, and showed equivalent peak/overall exposure, without apparent food effect. All AEs were mild and the safety profile was similar to other amphetamine formulations used for ADHD.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.