Objective: To identify and implement strategies to improve the efficiency of drug development in Phase 3 studies.

Background: Conducting global clinical trials can be challenging, including difficulties with patient selection, regional/cultural differences in the standard of care, utilization of patient reported outcomes (PROs), rater drift, the potential for large placebo effects and a complicated regulatory environment.

Methods: Based upon our Phase 2b experience with tozadenant (Hauser et al., 2014) and published literature of similar studies, we designed a Phase 3 study to assure that only qualified patients were enrolled by having their baseline clinical data reviewed prior to randomization. Training was developed for raters and patients in their local language, including education about how participating in a clinical trial differs from a typical doctor-patient interaction. Rigorous criteria was applied during site selection with an emphasis on prior clinical trial experience in PD. TOZ-PD is an ongoing Phase 3 study in fluctuating PD patients across 7 countries using 6 languages. The study will enroll 450 patients randomized 1:1:1 to receive tozadenant 60 mg BID, 120 mg BID or placebo for 24 weeks, followed by a 52-week open-label period. The primary endpoint is OFF time. This protocol was submitted to FDA as a Special Protocol Assessment (SPA) to ensure that TOZ-PD would be considered a pivotal study should the results be positive.

Results: A central review and approval process for qualifying all patients prior to entry was implemented. An independent 3rd party provides accreditation to raters at study start and conducts central rater review throughout the study to monitor for rater drift. Training videos were provided in all languages for the PROs. Study specific videos were produced for sites and patients on minimizing the placebo effect and what it means to participate in a clinical trial. TOZ-PD was granted a SPA Agreement Letter from FDA.

Conclusions: We were able to implement strategies to improve drug development efficiency and data integrity by obtaining regulatory acceptance for this phase 3 study, centralizing the patient eligibility process, accrediting and monitoring raters, and standardizing training materials for sites and trial participants.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/strategies-to-improve-drug-development-efficiency-through-regulatory-interactions-minimizing-the-placebo-effect-and-improving-data-integrity-within-a-phase-3-study-of-tozadenant-in-parkinsons-diseas/