BIOEQUIVALENCE ASSESSMENT OF A SINGLE 5 MG DAY TESTOSTERONE TRANSDERMAL SYSTEM VERSUS 2 2.5 MG/DAY SYSTEMS IN HYPOGONADAL MEN/

A novel, nonscrotal, transdermal delivery system for testosterone ther apy has been marketed for treatment of hypogonadal men. The usual dose of this system is two 2.5 mg/day systems applied daily. A new system has been developed that administers a dose of 5 mg/day using a single patch rather than two patches. A randomized, steady-state, four-period , replicate-design, open-label, crossover study was con ducted to asse ss the bioequivalence of the two testosterone transdermal delivery sys tems in postpubertal, hypogonadal men: two 2.5 mg/day patches as the r eference regimen (R) and one 5 mg/ day patch as the lest regimen (T). 21 men were enrolled, and 20 completed the study. Each subject was ran domly assigned to one of four sequences (R1-R2-T1-T2, T1-T2-R1-R2, R1- T1-T2-R2, T1-R1-R2-T2), such that each subject received each regimen d uring two study sessions. Two subjects were inadvertently treated acco rding to the sequence T1-R1-T2-R2. Patches were applied to the upper a rm, thigh, and back in the evening on days 1, 2, and 3, respectively, of each study session. Serial blood samples were obtained for pharmaco kinetic analysis of testosterone for 24 hours after patch application on day 3 of each study session. The two formulations would be consider ed bioequivalent if the 90% confidence intervals (CI) for the ratios o f the adjusted geometric means for T:R for both area under the concent ration-time curve from 0 to 24 hours (AUC(0-24)) and maximum concentra tion (C-max) were completely contained in the interval (0.80, 1.25). M ean values for AUC(0-24), and C-max were similar for the two formulati ons. The T and R formulations were found to be bioequivalent based on both AUC(0-24) (90% CI 0.96, 1.08) and C-max (90% CI 0.92, 1.07). The median time to C-max was also similar, indicating comparable rates of testosterone absorption for both formulations. Based on this analysis, the testosterone transdermal system 5 mg/day patch is bioequivalent t o two of the 2.5 mg/day patches. Both systems were safe and well toler ated in hypogonadal men.