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Abstract:
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Usually the dose levels for a Single Ascending Dose (SAD) or Multiple Ascending Dose (MAD) Phase 1 clinical study are based on pharmacokinetic (PK) and safety evaluation. But in one SAD/MAD study, we also want the dose levels studied to be able to achieve some degree of response for a PD biomarker, especially the highest dose for the top MAD panel. A Bayesian adaptive model-based approach was developed to achieve this goal. With this approach, the dose-response relationship was predicted/updated dynamically using Emax model based on observed data from the ongoing study combining with prior information from pre-clinical and clinical studies, and further the pre-specified dose for next dose panel was adaptively evaluated and adjusted during this study to achieve desired/target response level. A simulation was done to evaluate the characteristics of two dose selection strategies.
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