Effect of the Wetting Agent Sodium Lauryl Sulfate on the Pharmacokinetics of Alectinib: Results From a Bioequivalence Study in Healthy Subjects

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.