[1215] PHASE 2, RANDOMIZED, MULTICENTER, OPEN-LABEL STUDY OF ISA247 AND NEORAL IN POST-RENAL TRANSPLANT PATIENTS.
[Tomorrow the data from the transplantation trial will be presented. This is the abstract. I wonder if the article in WSJ will take some of the wind out of the sails. We should anyhow see some PR tomorrow. The side effect profile for ISA247 doesn't seem as superior as what was claimed by the company. Especially the "nervous system disorder" does not have a favorable ring to it. At least not in a psoriasis environment.
Erik]
Randall W. Yatscoff, Mark D. Abel, Launa J. Aspeslet, Robert T. Foster, Derrick G. Freitag, Robert B. Huizinga, Patrick R. Mayo, Daniel J. Trepanier. Isotechnika Inc., Edmonton, AB, Canada.
Purpose: The purpose of this 12 week study was three fold: To evaluate the calculated creatinine clearance of post-renal transplant patients receiving ISA247, to monitor safety parameters in post-renal transplant patients receiving ISA247, and to measure calcineurin inhibition and pharmacokinetics of ISA247 in post-renal transplant patients. Methods: Renal transplant patients (greater than 6 months post transplantation) with stable renal function (calculated creatinine clearance > 30 mL/min/1.73m) and on a stable dose of cyclosporine A were recruited to participate. Patients were randomized to receive either Neoral or ISA247, a new generation calcineurin inhibitor. Patients were evaluated at regular intervals for rejection, renal function, clinical biochemistry, side effects, drug pharmacokinetics and calcineurin inhibition as a pharmacodynamic marker. ISA247 and Neoral doses were titrated using C0. Results: This data analysis is based on n= 45 ISA247 and n = 51 Neoral patients having completed through day 70 of the study. A complete summary of all patients enrolled in the trial will be presented. Patient groups were similar for all demographic parameters. Calculated creatinine clearance has remained stable in both treatment groups with mean values at day 70 of 57.2 16.7 and 58.0 20.3 mL/min/1.73 m for ISA247 and Neoral, respectively. The most common adverse events for ISA247 and Neoral were gastrointestinal disorders (15% and 5%) and nervous system disorders (14% and 8%) of which headache was most common. The mean dose of ISA247 was 0.65 0.29 mg/kg compared with 1.1 0.2 mg/kg for Neoral. ISA247 Cmax and AUC were 171 96 ng/mL and 703 362 ng.h/mL, respectively. Neoral Cmax and AUC were 650 237 ng/mL and 2330 696 ng.h/mL. Less ISA247 exposure was associated with identical calcineurin inhibition to Neoral (ISA247 43 17% and Neoral 49 12%). Correlations between ISA247 C0, C2, and AUC(0-4) were r = 0.51 and r = 0.89, compared to Neoral of r = 0.05 and r = 0.47. ISA247 C0 directly correlated with calcineurin inhibition (r = 0.34) while Neoral did not (r = 0.01). Conclusions: Renal function has remained stable in both ISA247 and Neoral groups. ISA247 has a similar incidence of adverse events to Neoral despite 3-fold greater potency. ISA247 C0 strongly correlates with AUC and calcineurin inhibition suggesting C0 can be used for therapeutic drug monitoring.
Keywords: Calcineurin; Pharmacokinetics; Multicenter studies; Safety
Tuesday, June 3, 2003 5:00 PM |
