A39-10 Assessment of Pharmacokinetic Interactions between Admilparant (BMS-986278) and Nintedanib or Pirfenidone

Abstract Rationale Antifibrotic treatments for idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) include nintedanib and pirfenidone. Admilparant, a potent small molecule lysophosphatidic acid receptor 1 antagonist in development for IPF and PPF, may be coadministered with pirfenidone or nintedanib. As a result, dedicated clinical studies were conducted to assess potential pharmacokinetic (PK) interactions of admilparant when coadministered with nintedanib or pirfenidone. Methods The drug-drug interaction (DDI) potential between admilparant and antifibrotics at therapeutic levels was assessed using dedicated phase 1, open-label clinical studies in healthy volunteers (NCT06568458 and NCT03981094), and a population PK analysis using phase 2 clinical data (NCT04308681). In NCT06568458, admilparant and nintedanib DDI was assessed in a single-sequence, 3-period, multiple-dose, 2-way interaction, crossover design. In NCT03981094, admilparant and pirfenidone DDI was assessed in a 3-period, 3-treatment, randomized, crossover design. Plasma concentration data from validated bioanalytical methods were used to calculate PK parameters for admilparant, nintedanib, and pirfenidone alone and with admilparant in combination with each antifibrotic. Additionally, a population PK model, derived using phase 2 clinical data in patients with IPF and PPF (NCT04308681), was used to further explore these DDIs in a representative patient population. Results In NCT06568458, coadministration at steady state of admilparant (120 mg twice daily BID) and nintedanib (150 mg BID) had minimal effect on the PK of either drug vs administration alone; 90% confidence intervals (CIs) of geometric least squares mean (LSM) ratios for peak and systemic exposure parameters were mostly contained within the no-effect boundary (0.80-1.25) (Table). Similarly, in NCT03981094, after coadministration of admilparant (60 mg) with pirfenidone (801 mg), PK exposure parameters were comparable vs administration alone; 90% CIs of geometric LSM ratios were contained within the no-effect boundary (Table). Additionally, results from the population PK model analysis showed no clinically significant differences in admilparant exposure when administered alone or in combination with nintedanib or pirfenidone (Table). Admilparant both alone and coadministered with nintedanib or pirfenidone was safe and well tolerated. Conclusion Overall, results demonstrated no clinically significant DDI between admilparant and nintedanib or pirfenidone, suggesting potential flexible admilparant combination use, minimizing clinical management complexity, and potentially broadening treatment availability. This abstract is funded by: Bristol Myers Squibb