Abstract
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 <2x are permitted in future studies.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3495.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020