Single-Dose Comparative Pharmacokinetics of Two Formulations of Lenalidomide 25 mg in Healthy Subjects: A Randomized Crossover Study
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.
KeywordsBioequivalence Lenalidomide Pharmacokinetics
This study and the article processing fee in this journal were funded by the sponsor Samyang Biopharmaceutical Corp., Seongnam-si, Gyeonggi-do, Korea. Also this study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (grant number: HI14C1063) and a research fund of Chungnam National University and supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B04033515). All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Sang Yeob Park is an employee of Samyang Biopharmaceuticals Corp. Hye Jung Lim is an employee of Samyang Biopharmaceuticals Corp. Sa-Won Lee is an employee of Samyang Biopharmaceuticals Corp. Min-Hyo Seo is an employee of Samyang Biopharmaceuticals Corp. SeungHwan Lee, Jun Gi Hwang, JaeWoo Kim, and Jang Hee Hong have nothing to disclose.
Compliance with Ethics Guidelines
This study was conducted in accordance with the ethical principles of the 1964 Declaration of Helsinki and its later amendments, as well as the rules of Korean Good Clinical Practice. All subjects provided written informed consent after receiving a detailed explanation about the study prior to any study related procedures.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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