[P1–067]: USE OF EFLORNITHINE (DFMO) IN THE TREATMENT OF MILD ALZHEIMER's DISEASE: A COMPASSIONATE USE SINGLE‐CASE STUDY

predicted using two methods: simulations (which accounted for inter-individual variability and parameter uncertainty) and a less conservative, bias-corrected 90% confidence interval approach. Results: A small, positive relationship between azeliragon plasma concentration and QTcF was noted with a slope of 0.059 msec/ng/mL. Simulations predicted mean (90% prediction interval) changes in QTcF of 0.733 msec (0.32-1.66 msec) with the Phase 3 dose (5 mg QD stead state, predicted Cmax 11.0 ng/mL (5.24-23.7 ng/mL)) and 4.32 msec (1.78.74 msec) at supra-therapeutic doses (20 mg QD steady state or 60 mg QD x 6d, predicted Cmax 66.0 ng/mL (26.5-122.9 ng/mL)). Bias-corrected upper 90% confidence intervals for therapeutic and supra-therapeutic doses are 0.88 msec and 5.01 msec, respectively. Conclusions:The model-based analysis shows a small, non-clinically meaningful, positive relationship between azeliragon plasma concentration and QTcF with a slope close to zero. Neither the prediction interval nor the upper bound of the 90% confidence interval reach 10 msec, thus demonstrating no clinically meaningful (i.e. >5 msec prolongation) drug-related effect on QTcF at expected therapeutic and supratherapeutic doses of azeliragon.