(#134) Bioavailability and Tolerability of Lisdexamfetamine Dimesylate Oral Solution Versus Lisdexamfetamine Dimesylate Capsules in Healthy Volunteers

Abstract: Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug of dextroamphetamine approved for attention-deficit/hyperactivity disorder (ADHD) and for binge eating disorder in adults. Capsule formulations may be unsuitable for patients with dysphagia or aversion to solid oral dosage forms. To address this, a new oral solution (OS) formulation of LDX (10 mg/mL) was developed. This study assessed the bioavailability (BA), safety and palatability of LDX OS versus Vyvanse® 70 mg capsules under fasting conditions in healthy subjects. In a single-dose, randomized, open-label, two-period, two sequence, crossover study with ≥7-day washout, 32 healthy adults were randomized to receive 7 mL of 10 mg/mL LDX OS or Vyvanse® 70mg capsule. Blood samples were collected pre-dose and up to 72-hours post-dose; pharmacokinetic (PK) parameters, area under the curve (AUC), maximum concentration (Cmax), and time to Cmax (Tmax) were calculated using non-compartmental analysis. Bioequivalence was determined by 90% confidence intervals (CIs) for geometric mean ratios (GMRs) within the 80-125% FDA-accepted range. Palatability was assessed via organoleptic questionnaires. Twenty-eight subjects (17 males; 11 females) completed the study and demonstrated comparable absorption rates of dextroamphetamine to Vyvanse® 70 mg with geometric mean ratios (GMRs) of 110.8% (AUC0-4 hrs) 97.2% (AUC4 hrs-t), 98.7% (AUC0- infinity), and 100.8% (Cmax), all within the FDA's bioequivalence range. Palatability was favorable, with 86.7% rating LDX OS as easily acceptable. All 52 reported adverse events were mild or moderate; no serious events occurred. These findings support LDX OS as a bioequivalent, well-tolerated, and palatable alternative for patients who may have difficulty swallowing capsules.

Short Description: This randomized, cross-over study assessed the bioavailability (BA), safety and palatability of lisdexamphetamine oral solution (LDX OS) 10 mg/mL versus Vyvanse® 70 mg capsules in healthy volunteers. All pharmacokinetic parameters resulted in geometric mean ratios within the FDA-accepted range for bioequivalence. LDX OS was well tolerated, with only mild or moderate adverse events (52 in total) reported. Palatability was favorable, supporting LDX OS as a viable alternative for patients who have difficulty swallowing capsules.

Name of Sponsoring Organization(s): Azurity Pharmaceuticals, Inc.