Unveiling the Potential of Cmax f2 Factor Applied to Pilot Bioavailability/Bioequivalence Studies—A Case Study with Pazopanib Drug Products

<b>Background:</b> When companies are uncertain about the potential of a new formulation to be bioequivalent to a Reference product, it is common practice to carry out downsized pilot studies as a gatekeeping in vivo strategy to decide whether to move forward or not with a full-size pivotal study. However, due to the small study size, these studies are inarguably more sensitive to variability. <b>Objectives:</b> To address and mitigate the uncertainty of the conclusions of pilot studies concerning the maximum observed concentration (C_max), the <i>f</i>₂ factor was proposed as an alternative approach to the average bioequivalence statistical methodology. <b>Methods:</b> In this work, the alternative methodology is applied to pharmacokinetic data from pilot bioequivalence trials performed with pazopanib 200 mg and 400 mg. <b>Results:</b> Despite the small sample size, and very high intra-subject variability, the <i>f</i>₂ factor demonstrated the potential for predicting bioequivalence. The positive results were confirmed in the full sized pivotal studies. <b>Conclusions:</b> In conclusion, this alternate methodology shows promise in reducing uncertainty associated with pilot studies and aiding in decisions to go forward with pivotal bioequivalence studies.