Bioequivalence of lisdexamfetamine dimesylate hard capsules formulations

Lisdexamfetamine (LDX), an inactive prodrug of dexamphetamine, is used as a second-line treatment for attention deficit hyperactivity disorder (ADHD) and for moderate to severe binge eating disorder (BED). The objective of this study is to evaluate the bioequivalence of two LDX formulations, including the reference product manufactured by Patheon Pharmaceuticals (Venvanse® 70 mg) versus a formulation manufactured by Eurofarma Laboratórios S/A. A randomized, crossover, open-label study was conducted with two treatments, two periods, two sequences, and 48 healthy participants of both sexes who received oral administration of the medications. A total of 24 blood samples were collected from each participant, from T0 (before taking the medication) to 10 hours later. The plasma concentration of LDX was quantified using liquid chromatography coupled with mass spectrometry (LC-MS/MS). Both formulations were well tolerated, and no serious adverse events were reported. Cmax and AUC0-t were compared: the ratio between the test and reference formulations for Cmax was 106.22% with a 95% confidence interval (CI) of 97.72% - 116.66% and a power of 98.75%. The ratio between the test and reference formulations for AUC0-t was 106.28%, CI (100.68% - 112.19%), with a power of 100.00%. The ratio between the test and reference formulations for AUC0-inf was 106.29%, CI (100.71% - 112.17%), with a power of 100.00%. The formulations were shown to be statistically bioequivalent in terms of their rate and extent of absorption, based on criteria established by the Brazilian Health Regulatory Agency (ANVISA).