Phase 1, randomized, open-label, single-dose, crossover study to evaluate the bioequivalence of four formulations of oral rivoceranib tablets in healthy subjects.

person Janelle Weyer Celerion, Tempe, AZ info_outline Janelle Weyer, Xianzhang Meng, Lynda Finis, Bill Strickland, CheolHee Park, Seong Jang

Authors person Janelle Weyer Celerion, Tempe, AZ info_outline Janelle Weyer, Xianzhang Meng, Lynda Finis, Bill Strickland, CheolHee Park, Seong Jang Organizations Celerion, Tempe, AZ, Elevar Therapeutics, Salt Lake City, UT, Elevar Therapeutics, Inc., Salt Lake City, UT Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Elevar Therapeutics, Celerion Background: Rivoceranib is a novel oral tyrosine kinase inhibitor that potently and selectively inhibits VEGFR2. Rivoceranib is being investigated for indications targeted towards solid malignancies as either monotherapy or in combination with other anticancer therapies. Herein, we assessed the bioequivalence of a single dose of rivoceranib administered as 4 different formulations in healthy subjects. Methods: This single-center, open-label, randomized, single-dose, 4-way crossover study evaluated the bioequivalence of 4 different formulations of rivoceranib oral tablets in healthy adults. Each subject participated in 4 treatment periods, where they were randomized to 1 of 4 sequences: ABCD, BDAC, CADB, and DBAC (Formulation A = rivoceranib 250 mg tablet/clinical formulation used in the pivotal phase 3 study, Formulation B = rivoceranib 200 mg tablet/clinical formulation used in early clinical studies, Formulation C = rivoceranib 250 mg tablet/formulation to be developed for future use, Formulation D = rivoceranib 250 mg tablet/to-be-marketed formulation). Results: Of the 60 subjects enrolled, 66.7% were male, 88.3% were white, and median age was 43 years. The median plasma rivoceranib T max was similar following all treatments (2 hours post-dose). The 90% CIs around the geometric mean ratios (GMRs) of plasma rivoceranib AUC 0-t, AUC 0-inf , and C max for Formulation B vs. Formulation A and Formulation D vs. Formulation A were within the 80-125% reference interval, demonstrating bioequivalence between Formulation B and Formulation A as well as Formulation D and Formulation A. The 90% CIs around the GMRs of plasma rivoceranib AUC 0-t , AUC 0-inf , and C max for Formulation C vs. Formulation A were slightly outside of the 80%-125% reference interval. Conclusions: Formulations B (clinical formulation used in early clinical studies) and D (to-be-marketed formulation) were bioequivalent to Formulation A (clinical formulation used in the pivotal phase 3 study). Formulation C (formulation to be developed for future use) and Formulation A were similar, but the difference was slightly outside of the bioequivalence criteria. It remains to be evaluated whether the difference in bioavailability between Formulation C and Formulation A is clinically meaningful. Clinical trial information: NCT05287360. Summary of statistical comparisons of pharmacokinetic parameters of rivoceranib formulations. Formulation B vs A Formulation C vs A Formulation D vs A GMR AUC 0-t , 90% CI 96.22 - 114.92 * 106.21 - 126.72 92.86 - 110.79 GMR AUC 0-inf , 90% CI 98.07 - 116.12 * 106.41 - 126.11 93.24 - 110.39 GMR C max , 90% CI 87.99 - 113.68 * 97.04 - 125.20 87.44 - 112.82 * GMR of dose-normalized values.

Clinical