REDUCTIONS IN ANTIBODIES TO DOUBLE-STRANDED DNA IN LUPUS PATIENTS TREATED WITH ABETIMUS SODIUM IN INTERNATIONAL PHASE 3 STUDY

Matthew D. Linnik, PhD, Tenshang Joh, PhD, and Andrew Wiseman, PhD, La Jolla Pharmaceutical Company, San Diego, CA, USA

Abstract

Purpose. This study evaluated whether administration of a single intravenous 100mg or 300mg dose of abetimus sodium (LJP 394; abetimus) has the potential to increase QT wave prolongation in healthy volunteers.

Methods. This study was a single center, randomized, single-blind, placebo and positive-controlled study.  One hundred sixty subjects were randomized to receive one of four treatments, placebo, 400mg moxifloxican (positive control), 100mg or 300mg abetimus, and randomization was stratified by gender.  Twelve-lead electrocardiogram (ECG) data were digitally obtained for twenty-four hours of continuous recording on both Day 0 and Day 1. Individual ECGs were analyzed at multiple timepoints.  Three types of corrections from QT to QTc (corrected QT interval) were evaluated: QTcI (individually defined QTc), QTcB (QTc obtained by the Bazett’s formula), and QTcF (QTc obtained by the Fridericia’s formula).  Pharmacokinetic data was also collected.

Results.The placebo-corrected QtcI mean change from baseline for moxifloxican was 7 milliseconds (msec), thus, this study had the power to detect a QTc change of 5-10 msec.  After placebo correction, the 100mg dose demonstrated a mean change of 1.1 msec (p=0.4831), the 300mg dose demonstrated a mean change of 2.0 msec (p=0.3282).  Safety:  Abetimus was well tolerated.  100 of 160 subjects reported at least one adverse event.  The incidence of adverse events was similar between the placebo, 100mg and 300mg groups.  There were no serious adverse events and no subject discontinued the study due to an adverse event. Pharmacokinetics:  Cmax was 26.6 and 97.6 μg/ml, AUC was 17.1 and 75.4 μg*hr/ml, t1/2 was 0.90 and 0.98 hr and Vd was 7.8 and 6.5L for 100mg and 300mg, respectively.

Conclusion. Abetimus did not have a clinically relevant effect on any ECG parameter at either the 100mg or 300mg dose.  There was no relationship between plasma concentration of abetimus and change in QTc from baseline.  The two doses of abetimus were well tolerated.  Abetimus is being evaluated in an international Phase 3 clinical study at doses of 100mg, 300mg or 900mg per week.

Presented at the
The 8th International Congress on SLE
Shanghai, China
May 23-27, 2007