Abstract

Purpose: To implement an RTDA process, similar to that described in the FDA Guidance for Industry: Population Pharmacokinetics, during a Phase III trial of linezolid (IV to oral) in pediatric patients which utilized an every 8 hour dosing regimen.

Methods: During study enrollment, data was transmitted monthly; data merges were performed to generate population PK-specific queries; queries were communicated for resolution. Descriptive figures and tables were provided to sponsor for internal discussions. The impact of the new dosing regimen on linezolid plasma concentrations was evaluated on a monthly basis as well. As it was not known at the start of the study how many patients would have PK samples drawn during administration of the oral suspension, this was monitored throughout the study in order to prospectively plan the analysis.

Results: Approximately 50 figures and queries were generated each month and over 100 data issues were resolved proactively. The complicated process for merging of concentration data to CRF data was resolved prior to data lock, saving several weeks of dataset creation time.

Conclusions: Implementing RTDA improved data quality, reduced data exclusions, and facilitated rapid dataset creation upon data lock. This process allowed early confirmation of the appropriateness of the new dosing regimen. Dataset creation issues were proactively resolved and the analysis was prospectively designed, allowing the population PK/PD analysis to be included in the FDA submission.

American Society for Clinical Pharmacology and Therapeutics (ASCPT), Washington, DC, April 2003

By CM Rubino, ME McPhee, M Vo, GL Jungbluth