Effects of Quinidine or Rifampin Co‐administration on the Single‐Dose Pharmacokinetics and Safety of Rilzabrutinib (PRN1008) in Healthy Participants

Author:

Rask‐Madsen Christian1,Katragadda Suresh2,Li Mengyao3,Ucpinar Sibel3,Chinn Leslie3,Arora Puneet4,Smith Patrick5

Affiliation:

1. Translational Medicine and Clinical Pharmacology, Sanofi Cambridge MA USA

2. Department of Pharmacokinetics Dynamics and Metabolism, Sanofi Cambridge MA USA

3. Department of Pharmacokinetics Dynamics and Metabolism, Sanofi Bridgewater NJ USA

4. Department of Clinical Inflammation and Immunology, Sanofi South San Francisco CA USA

5. Integrated Drug Development, Certara Parsippany NJ USA

Abstract

AbstractThis open‐label, phase 1 study was conducted with healthy adult participants to evaluate the potential drug‐drug interaction between rilzabrutinib and quinidine (an inhibitor of P‐glycoprotein [P‐gp] and CYP2D6) or rifampin (an inducer of CYP3A and P‐gp). Plasma concentrations of rilzabrutinib were measured after a single oral dose of rilzabrutinib 400 mg administered on day 1 and again, following a wash‐out period, after co‐administration of rilzabrutinib and quinidine or rifampin. Specifically, quinidine was given at a dose of 300 mg every 8 hours for 5 days from day 7 to day 11 (N = 16) while rifampin was given as 600 mg once daily for 11 days from day 7 to day 17 (N = 16) with rilzabrutinib given in the morning of day 10 (during quinidine dosing) or day 16 (during rifampin dosing). Quinidine had no significant effect on rilzabrutinib pharmacokinetics. Rifampin decreased rilzabrutinib exposure (the geometric mean of Cmax and AUC0‐∞ decreased by 80.5% and 79.5%, respectively). Single oral doses of rilzabrutinib, with or without quinidine or rifampin, appeared to be well tolerated. These findings indicate that rilzabrutinib is a substrate for CYP3A but not a substrate for P‐gp.

Publisher

Wiley

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