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Effect of the Wetting Agent Sodium Lauryl Sulfate on the Pharmacokinetics of Alectinib: Results From a Bioequivalence Study in Healthy Subjects
Author(s) -
Morcos Peter N.,
Parrott Neil,
Banken Ludger,
Timpe Carsten,
Lindenberg Marc,
Guerini Elena,
Dall Georgina,
Bogman Katrijn,
Sturm Carolina,
Zeaiter Ali,
MartinFacklam Meret,
Phipps Alex
Publication year - 2016
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.299
Subject(s) - alectinib , bioequivalence , medicine , pharmacokinetics , crossover study , pharmacology , confidence interval , anaplastic lymphoma kinase , lung cancer , placebo , alternative medicine , pathology , malignant pleural effusion
The anaplastic lymphoma kinase (ALK) inhibitor alectinib is an effective treatment for ALK ‐positive non‐small‐cell lung cancer. This bioequivalence study evaluated the in vivo performance of test 3 formulations with the reduced wetting agent sodium lauryl sulfate (SLS) content. This randomized, 4‐period, 4‐sequence, crossover study compared alectinib (600 mg) as 25%, 12.5%, and 3% SLS hard capsule formulations with the reference 50% SLS clinical formulation in healthy subjects under fasted conditions (n = 49), and following a high‐fat meal (n = 48). Geometric mean ratios and 90% confidence intervals (CIs) for C max , AUC 0–last , and AUC 0–∞ of alectinib, its major active metabolite, M4, and alectinib plus M4 were determined for the test formulations versus the reference formulation. Bioequivalence was concluded if the 90%CIs were within the 80% to 125% boundaries. The 25% SLS formulation demonstrated bioequivalence to the reference 50% SLS formulation for C max , AUC 0–last , and AUC 0–∞ of alectinib, M4, and alectinib plus M4 under both fasted and fed conditions. Further reductions in SLS content (12.5% and 3% SLS) did not meet the bioequivalence criteria. Cross‐group comparisons showed an approximately 3‐fold positive food effect. Reducing SLS to 25% resulted in a formulation that is bioequivalent to the current 50% SLS formulation used in alectinib pivotal trials.