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

NCT01244620 | Terminated Phase 1 Results

• 1 other identifier: B1321056
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

A pharmacokinetic drug-drug interaction study between sitaxsentan and tadalafil and between sitaxsentan and sildenafil at the steady-state

Outcome Measures

Primary Outcomes (6)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

Secondary Outcomes (1)

• Plasma Decay Half-Life (t1/2)

  Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)

Study Arms (4)

Treatment A

EXPERIMENTAL

sitaxsentan 100 mg QD for 6 days (Treatment A)

Drug: sitaxentan

Treatment B

EXPERIMENTAL

tadalafil 40 mg QD for 6 days

Drug: tadalafil

Treatment C

EXPERIMENTAL

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

Drug: sitaxsentan; Drug: tadalafil

Treatment D

EXPERIMENTAL

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

Drug: sitaxsentan; Drug: sildenafil

Interventions

sitaxentan DRUG

sitaxsentan 100 mg QD for 6 days

Also known as: Thelin

Treatment A

tadalafil DRUG

tadalafil 40 mg QD for 6 days

Treatment B

sitaxsentan DRUG

sitaxsentan 100 mg QD for 6 days

Treatment C

sildenafil DRUG

sildenafil 20 mg TID for 6 days

Treatment D

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Investigational Site

Singapore, 188770, Singapore

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

sitaxsentan; Tadalafil; Sildenafil Citrate

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Purines

Limitations and Caveats

Study endpoints were not analyzed due to early termination.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2010
• First Posted: November 19, 2010
• Study Start: November 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: February 22, 2012
• Results First Posted: February 22, 2012

Record last verified: 2011-01

Locations

SG (1)