First-in-world oral solution formulation of enzalutamide: Bioequivalence versus soft-gel capsule to support patient-centric drug delivery.

Abstract

e17072 Background: Enzalutamide is a standard therapy for advanced prostate cancer. An oral solution formulation has been developed to improve patient convenience and to address the needs of patients with swallowing difficulties or those requiring alternative oral administration. This study evaluated the bioequivalence of a novel enzalutamide oral solution formulation compared with the reference soft-gel capsule formulation. Methods: This open label, randomized, two-treatment, two-period crossover study was conducted in healthy adult male subjects under fasting conditions. Subjects received a single 160 mg dose of the Test oral solution or the Reference soft-gel capsule in each period. Serial blood samples were collected up to 72 hours post dose. Primary pharmacokinetic endpoints included maximum plasma concentration and area under the plasma concentration time curve from time zero to 72 hours. Parameters were analyzed using analysis of variance on log-transformed data. Bioequivalence was concluded if the 90 percent confidence intervals for the Test to Reference geometric mean ratios were within the predefined acceptance range of 80 to 125 percent. Results: 37 subjects completed both periods and were included in the pharmacokinetic analysis. For the Reference, geometric mean maximum plasma concentration was 6276.85 ng/mL and AUC from time zero to 72 hours was 126902.97 ng·h/mL. For the Test oral solution, geometric mean maximum plasma concentration was 6594.35 ng/mL and AUC from time zero to 72 hours was 128485.08 ng·h/mL. The Test to Reference geometric mean ratios were 105.06 percent for maximum plasma concentration with a 90 percent CI of 98.97 to 111.52 percent and 101.25 percent for AUC from time zero to 72 hours with a 90 percent confidence interval of 98.35 to 104.23 percent. Both parameters met bioequivalence criteria. No clinically relevant safety findings were reported. Conclusions: The enzalutamide 160 mg per 5 mL oral solution was bioequivalent to the reference soft-gel capsule formulation under fasting conditions, with comparable systemic exposure and favorable tolerability. This first-in-world oral solution formulation represents a patient-centric alternative that may support improved accessibility for elderly patients with swallowing difficulties, increases compliance and warrants further clinical and therapeutic application. Statistical results of log transformed test versus reference product enzalutamide. Parameter Test Reference Difference n %CV Geometric Mean (Test) Geometric Mean (Reference) Ratio (%) 90% CI Power Conclusion LN_Cmax 8.7940 8.7446 0.0353 35 15.22% 6,594.3473 6,276.8537 105.06% 98.97% to 111.52% 99.98% YES LN_AUC0-72 11.7636 11.7512 0.0172 35 7.37% 128,485.08 126,902.97 101.25% 98.35% to 104.23% 100 % YES