Pharmacodynamic Model to Predict Ocular Itching Outcomes at 24 Hours Post-Treatment with Olopatadine (0.77% or 0.2%)
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Matthew L Fidler, M. Stat., Ph.D., Abhijit Narvekar, MS, MBBS, David Covert, Ramesh Sarangapani, Ph.D.
Rationale: Simulate 24-hour ocular itching assessments between olopatadine 0.2% and 0.7% treatments, in patients with high baseline itching severity.

Methods: A differential odds model characterized individual and population olopatadine ocular itching using 2 completed CAC trials. These trials graded itching from 0 (no itching) to 4 (unbearable itching).  Both vehicle and olopatadine reduced baseline itching.  A one-compartment KPD Emax model was used to model the effect of Olopatadine. The baseline itching severity was significant in the model, affecting both overall itching and magnitude of effect. This model simulated the proportion of patients achieving 24 hour itching control with olopatadine 0.2% and 0.7%, with baseline severities being screened so that 1/6 to 5/6 sampled baseline time-points would have scores of ≤ 2 to ≤ 3.5.

Results: The model predicted both mean scores and proportions of patients in itching categories. With increasing baseline severity, % population with 24-hour control for Olopatadine 0.7% increased over Olopatadine 0.2% (from 5% to 14% more control). This prediction was confirmed with retrospective clinical data analysis.

Conclusions: The model predicted more patients had 24-hour control with olopatadine 0.7% than olopatadine 0.2% regardless of baseline severity or magnitude of 24-hour control. This validated model can simulate large trials with high baseline itching, to estimate the patient response to itching relief at 24-hour between Olopatadine 0.7% and 0.2%.