Pulmonary Arterial HypertensionPhase 1NCT01244620
A Pharmacokinetic Drug-Drug Interaction (DDI) Study Between Sitaxsentan And Sildenafil, And Between Sitaxsentan And Tadalafil After Multiple Doses
A Phase 1 study testing sitaxentan, tadalafil and sitaxsentan in people with Pulmonary Arterial Hypertension, run by Pfizer at 1 site in Singapore.
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. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- sitaxentan, tadalafil and sitaxsentan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteSingapore
- Study dates
- Nov 2010to Dec 2010
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- sitaxentan, tadalafil, sitaxsentan, sildenafil
- Keywords
- A pharmacokinetic drug-drug interaction study between sitaxsentan and tadalafil and between sitaxsentan and sildenafil at the steady-state
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sitaxentanDrug
Also called Thelin
sitaxsentan 100 mg QD for 6 days
tadalafilDrug
tadalafil 40 mg QD for 6 days
sitaxsentanDrug
sitaxsentan 100 mg QD for 6 days
tadalafilDrug
tadalafil 40 mg QD for 6 days
sitaxsentanDrug
sitaxentan 100 mg QD for 6 days
sildenafilDrug
sildenafil 20 mg TID for 6 days
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | sitaxsentan 100 mg QD for 6 days (Treatment A) Receives: Drug: sitaxentan |
| Treatment B | Experimental | tadalafil 40 mg QD for 6 days Receives: Drug: tadalafil |
| Treatment C | Experimental | sitaxsentan 100 mg QD co-administered with tadalafil 40 mg QD for 6 days Receives: Drug: sitaxsentan; Drug: tadalafil |
| Treatment D | Experimental | sitaxsentan 100 mg QD co-administered with sildenafil 20 mg TID for 6 days Receives: Drug: sitaxsentan; Drug: sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2010 (estimated)
- Study startNov 2010
- Primary completionDec 2010
- Study completionDec 2010
Why it stopped: Safety Issue: The trial was prematurely terminated on Dec 9, 2010, due to safety concerns, specifically new emerging evidence of hepatic injury.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01244620
- Sponsor's protocol ID
- B1321056
- Status last verified
- Jan 2011
- First submitted
- 15 Nov 2010
- Last updated
- 22 Feb 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01244620
- Acronym / sponsor ID
- B1321056
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- A pharmacokinetic drug-drug interaction study between sitaxsentan and tadalafil and between sitaxsentan and sildenafil at the steady-state
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Safety Issue: The trial was prematurely terminated on Dec 9, 2010, due to safety concerns, specifically new emerging evidence of hepatic injury.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 19 Nov 2010 (estimated)
- Results
- Posted 22 Feb 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Experimental | Drug: sitaxentansitaxsentan 100 mg QD for 6 days (Treatment A) |
| Treatment B | Experimental | Drug: tadalafiltadalafil 40 mg QD for 6 days |
| Treatment C | Experimental | Drug: sitaxsentan, Drug: tadalafilsitaxsentan 100 mg QD co-administered with tadalafil 40 mg QD for 6 days |
| Treatment D | Experimental | Drug: sitaxsentan, Drug: sildenafilsitaxsentan 100 mg QD co-administered with sildenafil 20 mg TID for 6 days |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sitaxentanAlso: Thelinsitaxsentan 100 mg QD for 6 days | Drug | Treatment A |
| tadalafiltadalafil 40 mg QD for 6 days | Drug | Treatment B |
| sitaxsentansitaxsentan 100 mg QD for 6 days | Drug | Treatment C |
| tadalafiltadalafil 40 mg QD for 6 days | Drug | Treatment C |
| sitaxsentansitaxentan 100 mg QD for 6 days | Drug | Treatment D |
| sildenafilsildenafil 20 mg TID for 6 days | Drug | Treatment D |
Primary outcome
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)
Trough Plasma Concentrations (Ctrough)
Time frame: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Minimum or "trough"concentrations
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)
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)
Apparent Oral Clearance (CL/F)
Time frame: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
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)
Time frame: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
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.
1 secondary outcome
Plasma Decay Half-Life (t1/2)
Time frame: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sitaxentan, tadalafil and sitaxsentan in people with Pulmonary Arterial Hypertension, run by Pfizer at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Feb 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2012.