A Pharmacokinetic Drug-Drug Interaction (DDI) Study Between Sitaxsentan And Sildenafil, And Between Sitaxsentan And Tadalafil After Multiple Doses

Summary

Sitaxsentan has a low drug-drug interaction potential and it did not have a clinically relevant effect on pharmacokinetics of sildenafil (a CYP3A sensitive substrate and PDE5 inhibitor). Tadalafil did not have clinically relevant effect on pharmacokinetics of bosentan and ambrisentan. Based on overall clinical drug-drug interaction profiles, and in vitro CYP enzymes and transporter data, a clinically relevant drug-drug interaction between sitaxsentan and tadalafil is not expected. Sildenafil is not expected to affect sitaxsentan pharmacokinetics (PK), as sitaxsentan is a substrate of CYP3A4 and CYP2C9, where sildenafil did not show clinically relevant effect on PK of substrates of CYP3A4 and CYP2C9.

Timeline

Start

2010-11

Primary completion

2010-12

Completion

2010-12

Outcome

Outcome not reported

Stopped: “Safety Issue: The trial was prematurely terminated on Dec 9, 2010, due to safety concerns, specifically new emerging evidence of hepatic injury.”

Drugs

Indications