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

Pfizer

Status and phase: Terminated; Phase 1

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: sitaxentan; Drug: sitaxsentan; Drug: sildenafil; Drug: tadalafil

Study type: Interventional

Funder types: Industry

Identifiers

NCT01244620

B1321056

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 21 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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16 participants in 4 patient groups

Treatment A

Experimental group

Description:

sitaxsentan 100 mg QD for 6 days (Treatment A)

Treatment:

Drug: sitaxentan

Treatment B

Experimental group

Description:

tadalafil 40 mg QD for 6 days

Treatment:

Drug: tadalafil

Drug: tadalafil

Treatment C

Experimental group

Description:

sitaxsentan 100 mg QD co-administered with tadalafil 40 mg QD for 6 days

Treatment:

Drug: tadalafil

Drug: sitaxsentan

Drug: tadalafil

Drug: sitaxsentan

Treatment D

Experimental group

Description:

sitaxsentan 100 mg QD co-administered with sildenafil 20 mg TID for 6 days

Treatment:

Drug: sildenafil

Drug: sitaxsentan

Drug: sitaxsentan