PII-119 - IMPACT OF CRUSHING OR GRINDING ON THE RELATIVE BIOAVAILABILITY OF THE VENETOCLAX TABLETS.

S. Alaei¹, Y. Wang², R. Deng³, P. Marroum², R. Menon⁴, A. Salem⁵, D. Shiller⁴, Y. Luo⁴; ¹Abbvie Inc, Chicago, IL, AbbVie, ²AbbVie, ³Genentech/Roche, ⁴AbbVie Inc.,, North Chicago, IL, USA, ⁵AbbVie Inc..

Background: Venetoclax is a potent selective Bcl2 inhibitor currently approved for the treatment of several hematological malignancies as tablets. Not all patients can swallow whole tablets and intact tablets cannot be administered through nasogastric tubes. For these patients, crushing or grinding tablets is hence important. This study aimed to evaluate the oral bioavailability of crushed and ground venetoclax tablets relative to intact tablets after a high fat meal

Methods: An open label, randomized, 3 way, crossover study in 15 healthy adult females compared the oral bioavailability of 100 mg intact, crushed and finely ground venetoclax tablets administered after a high fat meal. Crushed and ground venetoclax tablets were prepared using different devices resulting in a range of particle size distribution. Pharmacokinetic parameters were calculated by noncompartmental analysis. To assess the bioavailability of crushed and ground tablets relative to the intact tablets, point estimates and 90% confidence intervals (CIs) of geometric mean ratios were generated for Cmax, AUCt and AUCinf

Results: Crushed and finely ground venetoclax tablets had similar bioavailability to the intact venetoclax tablets as the 90% confidence intervals of the geometric mean ratios for AUCt and AUCinf were within 0.800-1.250 of the intact tablets. The lower bound of 90%CI for the Cmax ratio for crushed venetoclax tablets extended slightly below 0.800 (to 0.796). Cmax ratio for finely ground venetoclax tablets was 26% lower compared to the intact venetoclax tablets (Table 1). The slightly lower Cmax observed with the altered regimens are not considered clinically significant as venetoclax AUC and average concentrations of the dosing period have been shown to correlate with its clinical efficacy

Conclusion: Administering crushed or whole venetoclax tablets results in similar total venetoclax exposures and bioavailability. Therefore, crushing or grinding venetoclax tablets as alternative methods of administration may be considered for patients who have difficulty swallowing whole venetoclax tablets. Similarity of venetoclax exposures between the crushed and ground tablet regimens indicates that the device used and the altered tablet particle size after crushing or grinding do not impact the overall bioavailability of venetoclax tablets in a clinically meaningful way