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

Pulmonary Arterial Hypertension Clinical Trial

Official title:

A Phase 1, Open Label, Randomized, Four Period, Crossover, Multiple Dose Study To Assess The Pharmacokinetic Interaction Between Sitaxsentan and Tadalafil and The Effect Of Sildenafil On Sitaxsentan PK In Healthy Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01244620
• Other study ID #: B1321056
• Status: Terminated
• Phase: Phase 1
• First received: November 15, 2010
• Last updated: January 18, 2012
• Start date: November 2010
• Est. completion date: December 2010

Study information

• Verified date: January 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• sitaxentan
sitaxsentan 100 mg QD for 6 days
• tadalafil
tadalafil 40 mg QD for 6 days
• sitaxsentan
sitaxsentan 100 mg QD for 6 days
• tadalafil
tadalafil 40 mg QD for 6 days
• sitaxsentan
sitaxentan 100 mg QD for 6 days
• sildenafil
sildenafil 20 mg TID for 6 days

Locations

Country	Name	City	State
Singapore	Pfizer Investigational Site	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)	No
Primary	Trough Plasma Concentrations (Ctrough)	Minimum or "trough"concentrations	Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)	No
Primary	Maximum Observed Plasma Concentration (Cmax)		Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)	No
Primary	Area Under the Curve of the 24 Hour Dosing Interval (AUC24)		Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)	No
Primary	Apparent Oral Clearance (CL/F)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)	No
Primary	Volume of Distribution at Steady State (Vss)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.	Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)	No
Secondary	Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)	No

External Links

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