eatment with ciclosporin for microemulsion, mycophenolate mofetil and steroids in the prevention of acute rejections. Of the 202 patients, 104 were randomised to basiliximab and 98 to placebo. The primary efficacy endpoint, time to first biopsy-proven acute rejection (BPAR) episode or treatment failure defined as graft loss, death or presumptive rejection within the first 6 months post transplantation, occurred in 16.7% of basiliximab-treated patients and 21.7% of placebo-treated patients. When borderline rejections were included in the primary efficacy endpoint, the rates were 26.0% and 23.9% respectively, with no statistically significant difference between the basiliximab- and placebo-treated groups (HR: 1.04, 90% CI: [0.64; 1.68]). The rates of BPAR were 9.4% in the basiliximab group and 17.4% in the placebo group (HR: 0.50, 90% CI: [0.25; 0.99]). When borderline rejections were included, the rates were 20.8% and 19.6% respectively (HR: 1.01, 90% CI: [0.59; 1.72]). The overall safety profiles were similar in both groups. The incidence rates of adverse events and the pattern of adverse events were comparable between the two treatment groups and to be expected for the treatment regimens and the underlying diseases.
Immunogenicity
Of 339 renal transplant patients treated with basiliximab and tested for anti-idiotype antibodies, 4 (1.2%) developed an anti-idiotype antibody response. In a clinical trial with 172 patients receiving basiliximab, the incidence of human antimurine antibody (HAMA) in renal transplantation patients treated with basiliximab was 2/138 in patients not exposed to muromonab-CD3 and 4/34 in patients who received muromonab-CD3 concomitantly. The available clinical data on the use of muromonab-CD3 in patients previously treated with basiliximab suggest that subsequent use of muromonab-CD3 or other murine anti-lymphocytic antibody preparations is not precluded.
5.2 Pharmacokinetic properties
Adults
Single-dose and multiple-dose pharmacokinetic studies have been conducted in adult patients undergoing kidney transplantation. Cumulative doses ranged from 20 mg up to 60 mg. Peak serum concentration following intravenous infusion of 20 mg over 30 minutes is 7.1±5.1 mg/l. There is a proportional increase in Cmax and AUC from 20 mg to 60 mg, the range of single-dose administrations tested. The volume of distribution at steady state was 8.6±4.1 l. The extent and degree of distribution to various body compartments have not been fully studied. In vitro studies using human tissues indicate that basiliximab binds only to activated lymphocytes and macrophages/monocytes. The terminal half-life was 7.2±3.2 days. Total body clearance was 41±19 ml/h.
No clinically relevant influence of body weight or gender on distribution volume or clearance has been observed in adult patients. Elimination half-life was not influenced by age, gender, or race.
Paediatric population
The pharmacokinetics of basiliximab were assessed in 39 paediatric de novo renal transplantation patients. In infants and children (age 1–11 years, n=25), the steady-state distribution volume was 4.8±2.1 l, half-life was 9.5±4.5 days and clearance was 17±6 ml/h. Distribution volume and clearance are reduced by about 50% compared to adult renal t
