| Popis: |
To assess the impact of patient age and weight on the pharmacokinetics (PK), testosterone (T) suppression and safety from four fixed dosing regimens (7.5, 22.5, 30, or 45 mg for 1-, 3-, 4-, or 6-months, respectively) of subcutaneous in situ gel delivered leuprolide acetate (Gel-LA) injected via the ATRIGEL Delivery System in patients with prostate cancer (PCa).Two patient populations were specified for analysis: a small cohort of surgically castrated PCa patients and a large, pooled population of PCa patients from four pivotal trials of Gel-LA. Two separate analyses of the impact of age and weight on study endpoints were conducted: (1) PK and safety of a single monthly dose of Gel-LA in a Phase 1 study with PCa patients who had undergone bilateral surgical orchiectomy ("Bilaterally orchiectomized male study"); (2) PK/pharmacodynamic (PD) effects and safety using pooled data from four pivotal trials assessing 1-, 3-, 4-, and 6-month dosing of Gel-LA in patients with advanced PCa, stratified by age and body weight (pivotal trials).Eight orchiectomized patients from the "Bilaterally orchiectomized male study" and 438 patients from the pivotal trials were included in the analyses. Age and body weight did not appear to affect the PK results in the orchiectomized patient population. Pooled pivotal trial data showed that serum T levels did not appear to be influenced by age or weight; ≥90% of patients across all age groups and ≥92% of patients across all weight groups achieved T ≤ 50 ng/dL by week 4. Median T levels for castration (T ≤ 50 ng/dL) were maintained from week 3 until the end of the study and all subgroups achieved median T ≤ 20 ng/dL by week 4. Patients from the orchiectomized patient study did not report any serious treatment-related adverse events (AEs) and there were no AE-related withdrawals from the study. The most common AEs were hot flashes and injection site events. The safety profiles from pivotal trials have been previously described and, as expected, were consistent with known effects of LHRH agonist therapy and suppression of T levels.PK and PD of Gel-LA appear to be unaffected by age and body weight, as demonstrated by persistence of effective drug levels through the dosing period and consistent T suppression across different ages and body weights. |
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