SUMMARY

• The recommended dose of ERLEADA is 240 mg (one 240 mg tablet or four 60 mg tablets) administered once daily.¹
• In a phase 1, bioequivalence study evaluating the pharmacokinetics (PK) and safety of apalutamide in healthy male participants who received a 240 mg tablet vs four 60 mg tablets as a single oral dose under fasted conditions, 240 mg tablet was found to be bioequivalent to four 60 mg tablets. A total of 18 (24.3%) participants experienced ≥1 treatment-emergent adverse events (TEAEs) during the study. No grade ≥4 TEAEs, serious TEAEs, or deaths were reported. The most commonly reported TEAEs (>5%) included asymptomatic Coronavirus Disease 2019 (COVID-19; n=5; 6.8%), hypertriglyceridemia (n=4; 5.4%), and decreased weight (n=4; 5.4%).^2,3

clinical DATA

Phase 1 Study

Yu et al (2023)² evaluated the bioequivalence and safety of one apalutamide 240 mg tablet relative to four apalutamide 60 mg tablets when administered to healthy male participants under fasted conditions (N=74).

Study Design/Methods

• Phase 1, randomized, open-label, single-center, single-dose, 2-part study.
• Each part consisted of a 2-sequence, 2period crossover design (N=95; part 1, n=74; part 2, n=21).
• Part 1: assessed the bioequivalence of 240 mg tablet relative to four 60 mg tablets under fasted conditions.
• Part 2: assessed the effect of food on the relative bioavailability of 240 mg tablets. As part 2 of the study was not focused on bioequivalence, results are not summarized below.
• Healthy male participants between 18-55 years of age with a body mass index (BMI) between 18-30 kg/m² and a body weight of ≥50 kg were eligible to participate.
• Participants were randomly assigned to treatment sequences and received 1 treatment under fasted conditions in each period. Each period administered four 60 mg tablets (reference drug) as a single 240 mg oral dose, one 240 mg tablet (test drug) as a single oral dose, or the reverse sequence.
• Endpoints: safety and PK analyses
• Pharmacokinetics:
  • The primary PK parameters evaluated after dosing included maximum plasma concentration (Cmax), time to reach C_max (t_max), time period between dosing and the time of the first measurable plasma concentration (t_lag), and area under the plasma concentration-time curve from time 0 to 72 hours (AUC0-72h).
  • To meet bioequivalence criteria, the 90% CI for the geometric mean ratio (GMR) for C_max and AUC_0-72h had to fall within the limit of 80-125%.

Results

Baseline Characteristics

• Overall, 74 participants were enrolled in part 1 of the study (treatment sequence with four 60 mg tablets [n=37]; treatment sequence with one 240 mg tablet [n=37]).
• There were 64 (86.5%) participants that completed the study. The 10 participants that discontinued the study were due to COVID-19 related adverse events (AEs; n=5), TEAEs (hypercholesterolemia, n=1), consent withdrawal (n=1), or other reasons (positive COVID-19 result, failed urine drug screen for cocaine and tetrahydrocannabinol; n=1 each).
• Participants were primarily White (86.5%), with a mean age of 38.5 years (standard deviation [SD], 8.9), and a mean BMI of 26.4 kg/m² (SD, 2.6).

Pharmacokinetics

• The PK results are summarized in Table: PK Data Analysis Set and Table: Statistical Analysis of PK Data. The 90% CIs for the GMR of C_max and AUC_0-72h were within the 80‑125% criteria for bioequivalence.

Safety

• TEAEs reported are summarized in Table: Summary of TEAEs.
• No grade ≥4 TEAEs, serious TEAEs, or deaths were reported.³
• The most commonly reported TEAEs (>5%) included asymptomatic COVID-19 (n=5; 6.8%), hypertriglyceridemia (n=4; 5.4%), and weight decreased (n=4; 5.4%).

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 07 February 2025.