Effects Of Sitaxsentan On Proteinuria, 24-Hour Blood Pressure, And Arterial Stiffness In Chronic Kidney Disease Subjects (FCRD01)

• ClinicalTrials.gov Identifier: NCT00810732
• Recruitment Status: Completed
• First Posted: December 18, 2008
• Last Update Posted: August 16, 2012
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: December 17, 2008
• First Posted Date: December 18, 2008
• Last Update Posted Date: August 16, 2012
• Study Start Date: May 2007
• Actual Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 17, 2008): The primary efficacy endpoint is the mean 24-hour urine total protein level change from baseline at week 6. [ Time Frame: baseline at week 6 ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: December 17, 2008): The secondary efficacy endpoints include the changes from Baseline to week 6 in total 24-hour ambulatory monitoring of systemic arterial BP, Absolute values of the carotid-femoral PWV. [ Time Frame: baseline at week 6 ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects Of Sitaxsentan On Proteinuria, 24-Hour Blood Pressure, And Arterial Stiffness In Chronic Kidney Disease Subjects
• Official Title: The Effects Of Sitaxsentan Once Daily Dosing On Proteinuria, 24-Hour Blood Pressure, And Arterial Stiffness In Subjects With Chronic Kidney Disease.
• Brief Summary: This study is being conducted to evaluate sitaxsentan dosing in subjects with chronic kidney disease.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Chronic Kidney Disease
• CRD

Intervention

• Drug: Sitaxsentan
  Sitaxsentan sodium 100 mg orally administered once daily (double blind arm)
  Other Name: Thelin
• Drug: Nifedipine
  Nifedipine = 30 mg extended release tablets, orally administered once daily (open label arm)
• Drug: Placebo
  Placebo for sitaxsentan, orally administered once daily (double blind arm)

Study Arms

• Experimental: Sitaxsentan
  Sitaxsentan sodium 100 mg orally administered once daily (double blind arm)
  Intervention: Drug: Sitaxsentan
• Active Comparator: Nifedipine
  Nifedipine 30 mg extended release tablets, orally administered once daily (open label arm)
  Intervention: Drug: Nifedipine
• Placebo Comparator: Placebo
  Placebo for sitaxsentan, orally administered once daily (double blind arm)
  Intervention: Drug: Placebo

Publications *

• Farrah TE, Anand A, Gallacher PJ, Kimmitt R, Carter E, Dear JW, Mills NL, Webb DJ, Dhaun N. Endothelin Receptor Antagonism Improves Lipid Profiles and Lowers PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) in Patients With Chronic Kidney Disease. Hypertension. 2019 Aug;74(2):323-330. doi: 10.1161/HYPERTENSIONAHA.119.12919. Epub 2019 Jun 10.
• Dhaun N, Yuzugulen J, Kimmitt RA, Wood EG, Chariyavilaskul P, MacIntyre IM, Goddard J, Webb DJ, Corder R. Plasma pro-endothelin-1 peptide concentrations rise in chronic kidney disease and following selective endothelin A receptor antagonism. J Am Heart Assoc. 2015 Mar 23;4(3):e001624. doi: 10.1161/JAHA.114.001624.
• Dhaun N, Moorhouse R, MacIntyre IM, Melville V, Oosthuyzen W, Kimmitt RA, Brown KE, Kennedy ED, Goddard J, Webb DJ. Diurnal variation in blood pressure and arterial stiffness in chronic kidney disease: the role of endothelin-1. Hypertension. 2014 Aug;64(2):296-304. doi: 10.1161/HYPERTENSIONAHA.114.03533.
• Dhaun N, Melville V, Blackwell S, Talwar DK, Johnston NR, Goddard J, Webb DJ. Endothelin-A receptor antagonism modifies cardiovascular risk factors in CKD. J Am Soc Nephrol. 2013 Jan;24(1):31-6. doi: 10.1681/ASN.2012040355. Epub 2012 Dec 14.
• Dhaun N, MacIntyre IM, Kerr D, Melville V, Johnston NR, Haughie S, Goddard J, Webb DJ. Selective endothelin-A receptor antagonism reduces proteinuria, blood pressure, and arterial stiffness in chronic proteinuric kidney disease. Hypertension. 2011 Apr;57(4):772-9. doi: 10.1161/HYPERTENSIONAHA.110.167486. Epub 2011 Feb 28.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 17, 2008): 27
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 2009
• Actual Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Has stage 1-5 chronic kidney disease (CKD) as defined by the Kidney Disease Outcomes Quality Initiative (K/DOQI) with proteinuria, including any of the following aetiologies: immunoglobulin (IgA) nephropathy, polycystic kidney disease (PCKD), congenital abnormalities, reflux nephropathy, focal segmental glomerulosclerosis, minimal change nephropathy, and membranous nephropathy.

Exclusion Criteria:

• Required peritoneal dialysis or haemodialysis.
• Has kidney disease due to diabetes mellitus, vasculitis, systemic lupus erythematosus, or known renovascular disease; antiglomerular basement membrane disease; or is on immunosuppressive medication.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT00810732
• Other Study ID Numbers: B1321005; B1321005
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: August 2012