Conditions: Pulmonary Arterial Hypertension
Keywords: A pharmacokinetic drug-drug interaction study between sitaxsentan and tadalafil and between sitaxsentan and sildenafil at the steady-state
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 16
Healthy volunteers: yes

Brief 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.

Detailed description:

Arms:
arm 1: sitaxsentan 100 mg QD for 6 days (Treatment A) arm 2: tadalafil 40 mg QD for 6 days arm 3: sitaxsentan 100 mg QD co-administered with tadalafil 40 mg QD for 6 days arm 4: sitaxsentan 100 mg QD co-administered with sildenafil 20 mg TID for 6 days

Interventions: intervention 1: sitaxentan intervention 2: tadalafil intervention 3: sitaxsentan intervention 4: tadalafil intervention 5: sitaxsentan intervention 6: sildenafil
Intervention descriptions: intervention 1: sitaxsentan 100 mg QD for 6 days intervention 2: tadalafil 40 mg QD for 6 days intervention 3: sitaxsentan 100 mg QD for 6 days intervention 4: tadalafil 40 mg QD for 6 days intervention 5: sitaxentan 100 mg QD for 6 days intervention 6: sildenafil 20 mg TID for 6 days

Protocol document: