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Trial record 1 of 1 for:    NCT01244620
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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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ClinicalTrials.gov Identifier: NCT01244620
Recruitment Status : Terminated (Safety Issue: The trial was prematurely terminated on Dec 9, 2010, due to safety concerns, specifically new emerging evidence of hepatic injury.)
First Posted : November 19, 2010
Results First Posted : February 22, 2012
Last Update Posted : February 22, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE November 15, 2010
First Posted Date  ICMJE November 19, 2010
Results First Submitted Date  ICMJE January 18, 2012
Results First Posted Date  ICMJE February 22, 2012
Last Update Posted Date February 22, 2012
Study Start Date  ICMJE November 2010
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2012)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 18, 2010)
  • Maximum plasma concentration (Cmax) of sitaxsentan and tadalafil [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post morning dose on Day 6 ]
  • Time to reach maximum plasma concentration (Tmax) [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post morning dose on Day 6 ]
  • Trough plasma concentrations (Ctrough) of sitaxsentan and tadalafil [ Time Frame: Predose on Days 1, 4, 5, and 6 ]
  • Area under the plasma concentration-time curve (AUC24) from Time Zero (0) to 24 Hours of sitaxsentan and tadalafil [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post morning dose on Day 6 ]
  • Apparent clearance (CL/F) of sitaxsentan and tadalafil [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post morning dose on Day 6 ]
  • Steady-state volume of distribution (Vss/F) of sitaxsentan and tadalafil [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post morning dose on Day 6 ]
  • Plasma half life (t1/2) of sitaxsentan and tadalafil [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post morning dose on Day 6 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2012)
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) ]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2010)
Number of subjects with adverse events [ Time Frame: Screening up to 10 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pharmacokinetic Drug-Drug Interaction (DDI) Study Between Sitaxsentan And Sildenafil, And Between Sitaxsentan And Tadalafil After Multiple Doses
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE
  • Drug: sitaxentan
    sitaxsentan 100 mg QD for 6 days
    Other Name: Thelin
  • Drug: tadalafil
    tadalafil 40 mg QD for 6 days
  • Drug: sitaxsentan
    sitaxsentan 100 mg QD for 6 days
  • Drug: sitaxsentan
    sitaxentan 100 mg QD for 6 days
  • Drug: sildenafil
    sildenafil 20 mg TID for 6 days
Study Arms  ICMJE
  • Experimental: Treatment A
    sitaxsentan 100 mg QD for 6 days (Treatment A)
    Intervention: Drug: sitaxentan
  • Experimental: Treatment B
    tadalafil 40 mg QD for 6 days
    Intervention: Drug: tadalafil
  • Experimental: Treatment C
    sitaxsentan 100 mg QD co-administered with tadalafil 40 mg QD for 6 days
    Interventions:
    • Drug: sitaxsentan
    • Drug: tadalafil
  • Experimental: Treatment D
    sitaxsentan 100 mg QD co-administered with sildenafil 20 mg TID for 6 days
    Interventions:
    • Drug: sitaxsentan
    • Drug: sildenafil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 18, 2010)
16
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2010
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Singapore
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01244620
Other Study ID Numbers  ICMJE B1321056
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP