Pharmacokinetics of AR19, an Immediate-Release Amphetamine Sulfate Formulation Designed to Deter Manipulation for Administration Via Nonoral Routes: Bioequivalence to Reference Racemic Amphetamine Sulfate, Dose Proportionality, and Food Effect

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: C max , AUC last , AUC inf , λ z , T ½ , and T max . Safety was assessed. Results: Bioequivalence, dose comparison, and food effect studies included 36, 24, and 36 participants. The 90% confidence intervals (CIs) of C max , AUC last , and AUC inf 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 C max /D, AUC last /D, and AUC inf /D for AR19 5 versus 30 mg had CIs within 80%–125%. Mean ± standard deviation (SD) T max 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 T max 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.