Effect of rifampin, a potent organic-anion-transporting polypeptide inhibitor (OATPi), on the PK of BMS-986278, a lysophosphatidic acid receptor (LPA1) antagonist

Introduction: BMS-986278 is being investigated as a treatment (tx) for idiopathic pulmonary fibrosis (IPF). In vitro studies demonstrated that OATP mediates human hepatic uptake of BMS-986278. Patients with IPF often receive concomitant medications, including OATPi. Aims and Objectives: To evaluate the effects of rifampin (rif) on the PK and tolerability of BMS-986278 in healthy adult participants (ppts). Methods: This was an open-label drug-interaction study. Fasted ppts received an oral dose of 30 mg BMS-986278 on d1 followed by a 7-d washout; on d8, ppts received an oral dose of 600 mg rif and 30 mg BMS-986278. Plasma PK was measured for BMS-986278 and rif; tolerability was monitored. Results: All 15 enrolled ppts completed the study (73% male, 73% white, mean [SD] age 46.1 [12.7] y and BMI 25.2 [2.7] kg/m2). Following coadministration with rif, BMS-986278 mean area under the curve from 0 to infinity (AUC0-inf) and maximum concentration (Cmax) were elevated by 3.13- and 2.75-fold, respectively, vs BMS-986278 alone. Median time to Cmax (Tmax) increased from 1.1 h (BMS-986278) to 2.0 h (BMS-986278+rif). Rif PK matched published data. BMS-986278+rif and BMS-986278 alone demonstrated a similar safety profile. Of 4 reported adverse events, 3 were mild (back pain, nausea, and presyncope) and 1 was moderate (constipation); none were deemed related to tx. Conclusions: BMS-986278+rif and BMS-986278 alone were generally well tolerated; increases in exposure up to 3x of BMS-986278 were observed with co-administration of rif. Concomitant OATPi medications anticipated to increase BMS-986278 exposure