Objectives: We evaluated the pharmacokinetics (PK) of an investigational immediate-release amphetamine (AMP) sulfate formulation (AR19) designed to deter nonoral administration versus reference racemic amphetamine sulfate (RA-AMPH). We investigated AMP bioavailability from AR19, the effect of taking AR19 with food or sprinkling the capsules on food, and dose proportionality. Methods: Participants received AR19 (20 mg) or reference RA-AMPH (20 mg) (bioequivalence study) or AR19 5 or 30 mg (dose comparison study). Food effect study participants received AR19 (20 mg) as intact capsule while fasted or after high-fat/-calorie meal, or as pellets sprinkled on applesauce or yogurt (≥6-day washout). Blood samples were analyzed for dextroamphetamine (d-AMP) and levoamphetamine (l-AMP) PK: Cmax, AUClast, AUCinf, λz, T½, and Tmax. Safety was assessed. Results: Bioequivalence, dose comparison, and food effect studies included 36, 24, and 36 participants. The 90% confidence intervals (CIs) of Cmax, AUClast, and AUCinf for AR19 20 mg versus reference RA-AMPH or AR19 with intact capsule and meal or sprinkled AR19 pellets on food versus fasted were between 80% and 125%. Dose-normalized Cmax/D, AUClast/D, and AUCinf/D for AR19 5 versus 30 mg had CIs within 80%-125%. Mean ± standard deviation (SD) Tmax was comparable for AMP (d-AMP; l-AMP) following AR19 20 mg (2.84 ± 1.05; 3.05 ± 1.22) versus reference RA-AMPH (2.52 ± 0.75; 2.75 ± 1.00), and AR19 5 mg (2.48 ± 0.57; 2.65 ± 0.65) versus AR19 30 mg (2.55 ± 0.56; 2.72 ± 0.65). Mean ± SD Tmax for AMP (d-AMP; l-AMP) was higher with intact capsule and meal (5.59 ± 1.57; 5.59 ± 1.59) versus fasted (2.85 ± 0.76; 2.97 ± 0.79). No serious adverse events were reported. Conclusion: AR19 was bioequivalent to reference RA-AMPH. Bioavailability was similar at doses between 5 and 30 mg and was not impacted by meal consumption or sprinkling on food. AR19 at tested doses was well tolerated.
Keywords: ADHD; amphetamine; bioavailability; bioequivalence; pharmacokinetic.