Aaps J
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Randomized Controlled Trial
Quantitative pharmacology approach in Alzheimer's disease: efficacy modeling of early clinical data to predict clinical outcome of tesofensine.
Effective therapeutic options for Alzheimer's disease (AD) are limited and much research is currently ongoing. The high attrition rate in drug development is a critical issue. Here, the quantitative pharmacology approach (QP-A) and model-based drug development (MBDD) provide a valuable opportunity to support early selection of the most promising compound and facilitate a fast, efficient, and rational drug development process. ⋯ The placebo effect was also implemented in the final PK/PD model based on a published placebo model developed in a large AD cohort. Various internal evaluation techniques confirmed the reliability and predictive performance of the PK/PD model, which also successfully predicted the 14-week PoC data. For tesofensine, the dose concentration-effect relationship has successfully been described in mild AD patients demonstrating the supportive value of PK/PD models in QP-A/MBDD in early phases of clinical development for decision-making.