A Pharmacokinetic Drug-Drug Interaction (DDI) Study Between Sitaxsentan And Sildenafil, And Between Sitaxsentan And Tadalafil After Multiple Doses
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension
Intervention: sitaxentan; tadalafil; sitaxsentan; tadalafil; sitaxsentan; sildenafil
Intervention description: sitaxsentan 100 mg QD for 6 days; tadalafil 40 mg QD for 6 days; sitaxsentan 100 mg QD for 6 days; tadalafil 40 mg QD for 6 days; sitaxentan 100 mg QD for 6 days; sildenafil 20 mg TID for 6 days
Intervention MeSH terms: Sildenafil Citrate; Tadalafil; Sitaxsentan
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: A pharmacokinetic drug-drug interaction study between sitaxsentan and tadalafil and between sitaxsentan and sildenafil at the steady-state

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male subjects and women of non-child bearing potential between the ages of 21
             and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities
             identified by a detailed medical history, full physical examination, including blood
             pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests.

          -  Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >45 kg (99 lbs).

          -  An informed consent document signed and dated by the subject or a legally acceptable
             representative.

          -  Subjects who are willing and able to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures.

        Exclusion Criteria:

          -  Evidence or history of clinically significant hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or
             allergic disease (including drug allergies, but excluding untreated, asymptomatic,
             seasonal allergies at time of dosing) or clinical findings at Screening.

          -  A positive urine drug screen.

          -  Subjects with hepatic dysfunction, defined as aspartate aminotransferase (AST) and/or
             alanine aminotransferase (ALT) >1.5 times the upper limit of the normal range at
             Screening. A retest may be done if AST and/or ALT within 1.5- to 2- times the upper
             limit of the normal range at Screening, and the average of the first and repeated test
             values should be used to decide the eligibility.