Pharmacokinetics of a New Amphetamine Extended-release Oral Liquid Suspension Under Fasted and Fed Conditions in Healthy Adults: A Randomized, Open-label, Single-dose, 3-treatment Study

• Published in: Clinical therapeutics Vol. 39; no. 12; pp. 2389 - 2398
• Main Authors: Sikes, Carolyn, Stark, Jeffrey G., McMahen, Russ, Engelking, Dorothy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2017; Elsevier Limited
• Subjects: ADHD; Adults; amphetamine; Amphetamines; Attention deficit hyperactivity disorder; Bioavailability; Blood pressure; Children & youth; Clinical trials; drug delivery; Drug dosages; Drug therapy; FDA approval; Food; food effect; Hyperactivity; Pharmacokinetics; Psychiatry; Quality of life; amphetamine; pharmacokinetics; ADHD; drug delivery; psychiatry; food effect
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2017.10.018

A new amphetamine extended-release liquid formulation (AMP XR-OS), intended for the treatment of attention-deficit/hyperactivity disorder, has been developed. This study was performed to determine if administration with food affected the rate of absorption or bioavailability of AMP XR-OS. The formulation was also compared with an equivalent dose of an extended-release mixed amphetamine salts reference product (30 mg) under fed conditions.
Thirty adult volunteers participated in this single-dose, open-label, randomized, 3-period, 3-treatment crossover study. Each participant received a single 15-mL dose of AMP XR-OS (equivalent to 30 mg of the reference drug) under fasted conditions, a single 15-mL dose of AMP XR-OS under fed conditions, and a single dose of the reference drug under fed conditions. A 7-day washout separated the 3 treatment periods. Blood samples were collected at predetermined time points and analyzed for d- and l-amphetamine. Pharmacokinetic parameters reported are AUC0–5, AUC0–last, AUC5–last, and AUC0–∞; Cmax; elimination t1/2; and Tmax. The geometric mean ratios and 90% CIs of Cmax, AUC0–last, and AUC0–∞were determined for the comparison of AMP XR-OS fed and fasted, and Cmax, AUC0–5, AUC5–last, and AUC0–∞ were calculated for AMP XR-OS compared with the reference drug under fed conditions. Safety was also assessed.
Twenty-nine subjects completed the study. Subjects were mostly male, white, and of Hispanic/Latino ethnicity with a mean age of 35.83 years and a mean BMI of 25.36kg/m2. The 90% CIs of Cmax, AUC0–last, and AUC0–∞ for AMP XR-OS fasted versus fed were within the accepted 80% to 125% range, indicating lack of a food effect. In the comparison of AMP XR-OS fed versus the reference product, Cmax, AUC5–last, and AUC0–∞ were within the range to establish bioequivalence; however, AUC0–5 was significantly higher for AMP XR-OS compared with that of the reference drug. This difference between products was likely due to the known delay of Tmax and decreased exposure when the extended-release mixed amphetamine salts reference product is administered with food. A total of 36 mild or moderate adverse events were reported; 1 subject withdrew due to an adverse event, and no deaths occurred. These adverse events were consistent with the known pharmacodynamic effects of amphetamine.
The absence of a food effect may allow for AMP XR-OS to be administered with or without a meal.