on)Cmax, Cmin, and partial AUC were 2.4 ± 1.5 mcg/mL, 1.2 ± 0.7 mcg/mL, and 297 ± 166 mcg•h/mL, respectively, forpatients treated with 50 mg etanercept once weekly (N = 21); and 2.6 ± 1.2 mcg/mL, 1.4 ± 0.7 mcg/mL, and316 ± 135 mcg•h/mL for patients treated with 25 mg etanercept twice weekly (N = 16).
Patients with JIA (ages 4 to 17 years) were administered 0.4 mg/kg of etanercept twice weekly (up to a maximumdose of 50 mg per week) for up to 18 weeks. The meanserum concentration after repeated SC dosing was2.1 mcg/mL, with a range of 0.7 to 4.3 mcg/mL. Limited data suggest that the clearance of etanercept is reducedslightly in children ages 4 to 8 years. Population pharmacokinetic analyses predict that the pharmacokineticdifferences between the regimens of 0.4 mg/kg twice weekly and 0.8 mg/kg once weekly in JIA patients are of thesame magnitude as the differences observed between twice weekly and weekly regimens in adult RA patients.
The mean (± SD) serum steady-state trough concentrations for the 50 mg QW dosing in adult PsO subjects were1.5 ± 0.7 mcg/mL. Pediatric PsO patients (age 4 to 17 years) were administered 0.8 mg/kg of etanercept once weekly(up to a maximum dose of 50 mg per week) for up to 48 weeks. The mean (± SD) serum steady-state trough
concentrations ranged from 1.6 ± 0.8 to 2.1 ± 1.3 mcg/mL at weeks 12, 24, and 48.
In clinical studies with etanercept, pharmacokinetic parameters were not different between men and women and didnot vary with age in adult patients. The pharmacokinetics of etanercept were unaltered by concomitant MTX in RApatients. No formal pharmacokinetic studies have been conducted to examine the effects of renal or hepaticimpairment on etanercept disposition.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been conducted to eva luate the carcinogenic potential of etanercept products ortheir effect on fertility.
14 CLINICAL STUDIES
14.1 Adult Rheumatoid Arthritis
The safety and efficacy of etanercept were assessed in four randomized, double-blind, controlled studies. The resultsof all four trials were expressed in percentage of patients with improvement in RA using ACR response criteria.
Study I eva luated 234 patients with active RA who were ≥ 18 years old, had failed therapy with at least one but nomore than four disease-modifying antirheumatic drugs (DMARDs) (eg, hydroxychloroquine, oral or injectable gold,MTX, azathioprine, D-penicillamine, sulfasalazine), and had ≥ 12 tender joints, ≥ 10 swollen joints, and eithererythrocyte sedimentation rate (ESR) ≥ 28 mm/hr, C-reactive protein (CRP) > 2.0 mg/dL, or morning stiffness for≥ 45 minutes. Doses of 10 mg or 25 mg etanercept or placebo were administered SC twice a week for 6 consecutivemonths.
Study II eva luated 89 patients and had similar inclusion criteria to Study I except that patients in Study II hadadditionally received MTX for at least 6 months with a stable dose (12.5 to 25 mg/week) for at least 4 weeks and theyhad at least 6 tender or painful joints. Patients in Study II received a dose of 25 mg etanercept or placebo SC twice aweek for 6 months in addition to their stable MTX dose.
Study III compared the efficacy of etanercept to MTX in patients with active RA. This study eva luated 632 patientswho were ≥ 18 years old with early (≤ 3 years disease duration) active RA, had never receive |
