Single-Dose Comparative Pharmacokinetics of Two Formulations of Lenalidomide 25 mg in Healthy Subjects: A Randomized Crossover Study

SeungHwan Lee, Jun Gi Hwang, Sang Yeob Park, Hye Jung Lim, Sa-Won Lee, Min-Hyo Seo, JaeWoo Kim, Jang Hee Hong

Lenalidomide is used for the treatment of multiple myeloma in combination with dexamethasone. The purpose of this study was to compare the pharmacokinetics (PKs) and assess the bioequivalence of two formulations of lenalidomide 25 mg: Lenalid® 25 mg tablet (test formulation) and Revlimid® 25 mg capsule (reference formulation). A randomized, single-dose, two-treatment, two-period, two-sequence crossover study was conducted in 42 healthy subjects. All subjects were randomly assigned to one of the two sequences, and they received a single dose of test or reference formulation in the first period and the alternative formulation during the next period under fasting conditions. Serial blood samples for PK evaluation were collected up to 24 h post-dose and the PK parameters were estimated by non-compartmental methods. Throughout the study, tolerability was assessed on the basis of adverse events, vital signs, and clinical laboratory tests. The test formulation showed similar PK profiles to those of the reference formulation. The geometric mean ratio and 90% confidence interval (CI) of the test formulation to the reference formulation for maximum plasma concentration (Cmax) was 0.9995 (0.9250-1.0799) and the corresponding value for the area under the concentration-time curve from time zero to time of last quantifiable concentration (AUCt) was 0.9648 (0.9451-0.9850). Both CIs were within the conventional bioequivalence range of 0.8-1.25. The tolerability profile was not significantly different between the two formulations. This study found that the PKs of the two formulations of lenalidomide 25 mg were similar and the test formulation met the regulatory criteria for assuming bioequivalence with the reference formulation. Samyang Biopharmaceutical Corp.