Back to resultsA Pharmacokinetic Drug-Drug Interaction (DDI) Study Between Sitaxsentan And Sildenafil, And Between Sitaxsentan And Tadalafil After Multiple Doses
Primary Purpose
Pulmonary Arterial Hypertension
Status
Terminated
Phase
Phase 1
Locations
Singapore
Study Type
Interventional
Intervention
sitaxentan
tadalafil
sitaxsentan
tadalafil
sitaxsentan
sildenafil
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring A pharmacokinetic drug-drug interaction study between sitaxsentan and tadalafil and between sitaxsentan and sildenafil at the steady-state
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.
Sites / Locations
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Treatment A
Treatment B
Treatment C
Treatment D
Arm Description
sitaxsentan 100 mg QD for 6 days (Treatment A)
tadalafil 40 mg QD for 6 days
sitaxsentan 100 mg QD co-administered with tadalafil 40 mg QD for 6 days
sitaxsentan 100 mg QD co-administered with sildenafil 20 mg TID for 6 days
Outcomes
Primary Outcome Measures
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Trough Plasma Concentrations (Ctrough)
Minimum or "trough"concentrations
Maximum Observed Plasma Concentration (Cmax)
Area Under the Curve of the 24 Hour Dosing Interval (AUC24)
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.
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.
Secondary Outcome Measures
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01244620
Brief Title
A Pharmacokinetic Drug-Drug Interaction (DDI) Study Between Sitaxsentan And Sildenafil, And Between Sitaxsentan And Tadalafil After Multiple Doses
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2011
Overall Recruitment Status
Terminated
Why Stopped
Safety Issue: The trial was prematurely terminated on Dec 9, 2010, due to safety concerns, specifically new emerging evidence of hepatic injury.
Study Start Date
November 2010 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
A pharmacokinetic drug-drug interaction study between sitaxsentan and tadalafil and between sitaxsentan and sildenafil at the steady-state
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment A
Arm Type
Experimental
Arm Description
sitaxsentan 100 mg QD for 6 days (Treatment A)
Arm Title
Treatment B
Arm Type
Experimental
Arm Description
tadalafil 40 mg QD for 6 days
Arm Title
Treatment C
Arm Type
Experimental
Arm Description
sitaxsentan 100 mg QD co-administered with tadalafil 40 mg QD for 6 days
Arm Title
Treatment D
Arm Type
Experimental
Arm Description
sitaxsentan 100 mg QD co-administered with sildenafil 20 mg TID for 6 days
Intervention Type
Drug
Intervention Name(s)
sitaxentan
Other Intervention Name(s)
Thelin
Intervention Description
sitaxsentan 100 mg QD for 6 days
Intervention Type
Drug
Intervention Name(s)
tadalafil
Intervention Description
tadalafil 40 mg QD for 6 days
Intervention Type
Drug
Intervention Name(s)
sitaxsentan
Intervention Description
sitaxsentan 100 mg QD for 6 days
Intervention Type
Drug
Intervention Name(s)
tadalafil
Intervention Description
tadalafil 40 mg QD for 6 days
Intervention Type
Drug
Intervention Name(s)
sitaxsentan
Intervention Description
sitaxentan 100 mg QD for 6 days
Intervention Type
Drug
Intervention Name(s)
sildenafil
Intervention Description
sildenafil 20 mg TID for 6 days
Primary Outcome Measure Information:
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame
Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Title
Trough Plasma Concentrations (Ctrough)
Description
Minimum or "trough"concentrations
Time Frame
Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Title
Maximum Observed Plasma Concentration (Cmax)
Time Frame
Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Title
Area Under the Curve of the 24 Hour Dosing Interval (AUC24)
Time Frame
Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Title
Apparent Oral Clearance (CL/F)
Description
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.
Time Frame
Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Title
Volume of Distribution at Steady State (Vss)
Description
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.
Time Frame
Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Secondary Outcome Measure Information:
Title
Plasma Decay Half-Life (t1/2)
Description
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame
Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Singapore
ZIP/Postal Code
188770
Country
Singapore
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1321056&StudyName=A%20Pharmacokinetic%20Drug-Drug%20Interaction%20%28DDI%29%20Study%20Between%20Sitaxsentan%20And%20Sildenafil%2C%20And%20Between%20Sitaxsentan%20And%20Tadalafil%20After%20Mult
Description
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A Pharmacokinetic Drug-Drug Interaction (DDI) Study Between Sitaxsentan And Sildenafil, And Between Sitaxsentan And Tadalafil After Multiple Doses
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