Clinical trial NCT01200394: A Phase 2, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of PF-00489791 In Patients With Type 2 Diabetes And Overt Nephropathy
Official title: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ONCE-DAILY ADMINISTRATION OF A PHOSPHODIESTERASE 5 INHIBITOR (PF-00489791) IN ADULTS WITH TYPE 2 DIABETES AND OVERT NEPHROPATHY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathies
Keywords: Diabetic nephropathy
chronic kidney disease
PF-00489791
phosphodiesterase
PDE5
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-09-13
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: PF-00489791 is an inhibitor of phosphodiesterase type 5. Our hypothesis is that PF-00489791 will enhance the relaxation of blood vessels within the kidney and so reduce blood pressure, improving renal function.


Eligibility criteria: Inclusion Criteria:

* Male or female subjects greater than or equal to 18 years. Female subjects must be of non-child bearing potential.
* Clinical diagnosis of type 2 diabetes together with stages 3a, 3b or 4 CKD, based on an eGFR of 25-59 mL/min/1.73m2.
* Evidence of persistent, overt albuminuria; defined as a UACR greater than or equal to 300 mg/g (greater than or equal to 33.9 mg/mmol) for greater than 3 months.

Exclusion Criteria:

* Subjects with CKD resulting from type 1 diabetes or non-diabetic CKD.
* Subjects with poorly controlled diabetes mellitus, defined as HbA1C \>9%.
* Subjects on combination ACE inhibitor/ARB therapy.

Primary outcomes:
measure: Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 12
timeFrame: Baseline, Week 12 (Day 5, 6, 7)
Secondary outcomes:
measure: Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 3, 6 and 16
timeFrame: Baseline, Week 3 (Day 5, 6, 7), Week 6 (Day 5, 6, 7), Week 16 (Day 5, 6, 7)
measure: Change From Baseline in Urinary Protein Creatinine Ratio (UPCR) at Week 3, 6, 12, and 16
timeFrame: Baseline, Week 3 (Day 5, 6, 7), Week 6 (Day 5, 6, 7), Week 12 (Day 5, 6, 7), Week 16 (Day 5, 6, 7)
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 3, 6, 12, and 16
timeFrame: Baseline, Week 3, 6, 12, 16 (follow-up)
measure: Systolic, Diastolic and Mean Blood Pressure at Week 0, 3, 6, 12, and 16
timeFrame: Week 0, 3, 6, 12, 16 (follow-up)
measure: Change From Baseline in Serum Creatinine Concentration at Week 3, 6, 12, and 16
timeFrame: Baseline, Week 3, 6, 12, 16 (follow-up)
measure: Change From Baseline in Urine Transforming Growth Factor (TGF) Beta-1 Concentration at Week 3, 6, 12, and 16
timeFrame: Baseline, Week 3, 6, 12, 16 (follow-up)
measure: Change From Baseline in Serum High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 12 and 16
timeFrame: Baseline, Week 12, 16 (follow-up)
measure: Change From Baseline in Serum Cystatin-C Concentration at Week 12 and 16
timeFrame: Baseline, Week 12, 16 (follow-up)
measure: Plasma Concentration Versus Time Summary of PF-00489791
timeFrame: Pre-dose at Day 1 of Week 0, 3, 6 and 12; 4 hours post-dose on Day 1 of Week 0, 3 and 6
Other outcomes:
measure: Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) Level at Week 12 and 16
timeFrame: Baseline, Week 12, 16 (follow-up)
measure: Number of Participants With Vital Signs Abnormalities
timeFrame: Baseline up to Week 16 (follow-up)
measure: Number of Participants With Edema and Fluid Overload
timeFrame: Week 0, 3, 6, 12, 16 (follow-up)
measure: Number of Participants With Increased Use of Diuretics
timeFrame: Baseline up to Week 16 (follow-up)
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline up to Week 16 (follow-up)
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 16 (follow-up)
Locations:
city: Huntsville
country: United States
facility: Saadat Ansari Internal Medicine
state: Alabama
city: Huntsville
country: United States
facility: The Office of Iqbal Saeed MD, LLC
state: Alabama
city: Glendale
country: United States
facility: AKDHC Medical Research Services, LLC*
state: Arizona
city: Tempe
country: United States
facility: Southwest Clinical Research Institute, LLC
state: Arizona
city: Tempe
country: United States
facility: Southwest Clinical Research Institute, LLC
state: Arizona
city: Azusa
country: United States
facility: North America Research Institute
state: California
city: Azusa
country: United States
facility: North American Research Institute / California Kidney Specialist
state: California
city: Covina
country: United States
facility: Citrus Dialysis Center
state: California
city: La Mesa
country: United States
facility: California Institute of Renal Research
state: California
city: Sacramento
country: United States
facility: Capital Nephrology Clinical Research
state: California
city: San Dimas
country: United States
facility: California Kidney Specialists
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Whittier
country: United States
facility: Whittier Internal Medicine Nephrology Medical Group
state: California
city: Yuba
country: United States
facility: North Valley Nephrology
state: California
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Hialeah
country: United States
facility: Palm Springs Research Institute
state: Florida
city: Jupiter
country: United States
facility: ASA Clinical Research, LLC
state: Florida
city: Summerfield
country: United States
facility: Lakeview Medical Research
state: Florida
city: Conyers
country: United States
facility: Rockdale Medical Research Associates
state: Georgia
city: Macon
country: United States
facility: Renal Physicians of Georgia
state: Georgia
city: Meridian
country: United States
facility: Boise Kidney and Hypertension Institute
state: Idaho
city: Chicago
country: United States
facility: Chicago Clinical Research Institute, Inc.
state: Illinois
city: Evergreen Park
country: United States
facility: Associates in Nephrology, SC
state: Illinois
city: Evergreen Park
country: United States
facility: Research by Design, LLC
state: Illinois
city: Peoria
country: United States
facility: RenalCare Associates
state: Illinois
city: Elwood
country: United States
facility: Investigative Clinical Research of Indiana, LLC
state: Indiana
city: Wichita
country: United States
facility: Kansas Nephrology Research Institute, LLC
state: Kansas
city: Paducah
country: United States
facility: Four Rivers Clinical Research, Inc.
state: Kentucky
city: Metairie
country: United States
facility: Crescent City Clinical Research Center
state: Louisiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology
state: Louisiana
city: Rockville
country: United States
facility: Biolab Research, LLC
state: Maryland
city: Dearborn
country: United States
facility: Alzohaili Medical Consultants
state: Michigan
city: Flint
country: United States
facility: Apex Medical Research, AMR, Inc.
state: Michigan
city: Flint
country: United States
facility: Apex Medical Research, MI, Inc.
state: Michigan
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Lincoln
country: United States
facility: Lincoln Nephrology and Hypertension
state: Nebraska
city: Lincoln
country: United States
facility: Nebraska Nephrology Research Institute, LLC - Research Management, Inc.
state: Nebraska
city: Las Vegas
country: United States
facility: Alliance Against Diabetes
state: Nevada
city: Las Vegas
country: United States
facility: Clinical Research Consortium
state: Nevada
city: Bronx
country: United States
facility: Jacobi Medical Center - Department of Medicine - Nephrology
state: New York
city: Asheville
country: United States
facility: Mountain Kidney and Hypertension Associates, PA
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates
state: North Carolina
city: Willoughby Hills
country: United States
facility: Lake Medical Research
state: Ohio
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center, LLC
state: Pennsylvania
city: Uniontown
country: United States
facility: Preferred Primary Care Physicians, Inc.
state: Pennsylvania
city: Columbia
country: United States
facility: Columbia Nephrology Associates, PA
state: South Carolina
city: Greenville
country: United States
facility: Carolina Nephrology, PA
state: South Carolina
city: Orangeburg
country: United States
facility: Palmetto Nephrology, PA
state: South Carolina
city: Orangeburg
country: United States
facility: South Carolina Nephrology & Hypertension Ctr, Inc
state: South Carolina
city: Orangeburg
country: United States
facility: South Carolina Nephrology and Hypertension Center
state: South Carolina
city: Austin
country: United States
facility: Central Texas Kidney Associates
state: Texas
city: Austin
country: United States
facility: Research Management, Inc.
state: Texas
city: Houston
country: United States
facility: Diagnostic Clinic of Houston, PA
state: Texas
city: Houston
country: United States
facility: Houston Nephrology Research
state: Texas
city: Houston
country: United States
facility: Research Across America
state: Texas
city: San Antonio
country: United States
facility: Renal Associates, PA
state: Texas
city: San Antonio
country: United States
facility: San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
state: Texas
city: Fairfax
country: United States
facility: Nephrology Associates of Northern Virginia, Inc.
state: Virginia
city: Mechanicsville
country: United States
facility: Nephrology Specialists, P.C.
state: Virginia
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
city: Bremerton
country: United States
facility: Renal Remission & Hypertension Consultants, PLLC
state: Washington
city: Port Orchard
country: United States
facility: Sound Medical Research
state: Washington
city: Silverdale
country: United States
facility: Renal Remission and Hypertension Clinic
state: Washington
city: Gosford
country: Australia
facility: Renal Research Practice
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: New Lambton
country: Australia
facility: Department of Nephrology
state: Newcastle
city: New Lambton
country: Australia
facility: Pharmacy Department
state: Newcastle
city: Reservoir
country: Australia
facility: Melbourne Renal Research Group
state: Victoria
city: Calgary
country: Canada
facility: Sheldon M Chumir Health Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Brampton
country: Canada
facility: Entralogix Clincal Research Inc.
state: Ontario
city: Brampton
country: Canada
facility: Entralogix Clinical Research Inc.
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Oakville
country: Canada
facility: Entralogix Clinical Research Inc.
state: Ontario
city: Toronto
country: Canada
facility: N/A - formerly with Entralogix SMO
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Greenfield Park
country: Canada
facility: Centre de sante et de services sociaux champlain-Charles-Le Moyne
state: Quebec
city: Montreal
country: Canada
facility: Centre de Dialyse de Bois de Boulogne
state: Quebec
city: Montreal
country: Canada
facility: Hopital de Sacre Coeur de Montreal
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Nephrology Group, Nurses Redisence
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Nephrology Group, Nurses Residence
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Nephrology Group
state: Saskatchewan
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital (Aarhus Sygehus)
city: Copenhagen Oe
country: Denmark
facility: Rigshospitalet
city: Gentofte
country: Denmark
facility: Steno Diabetes Center
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Pokfulam
country: Hong Kong
facility: Division of Nephrology, Dept. of Medicine
city: Pokfulam
country: Hong Kong
facility: Division of Nephrology
city: Quarry Bay
country: Hong Kong
facility: ICON Clinical Research
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Hyderabad
country: India
facility: Apollo Hospitals
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Gujarat Kidney Foundation
state: Gujarat
city: Ahmedabad
country: India
facility: Shrushrut Clinical Research Association
state: Gujarat
city: Mumbai
country: India
facility: P. D. Hinduja National Hospital and Medical Research Centre
state: Maharashtra
city: Mumbai
country: India
facility: Pfizer Centre
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
state: Maharashtra
city: Pune
country: India
facility: Diabetes Care and Research Centre
state: Maharashtra
city: Pune
country: India
facility: KE.M Hospital Research Centre
state: Maharashtra
city: Pune
country: India
facility: King Edward Memorial Hospital
state: Maharashtra
city: Pune
country: India
facility: Jehangir Clinical Development Centre Pvt. Ltd.
state: Maharashtra
city: Seongnam-si
country: Korea, Republic of
facility: Pharmacy
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Clinical Trial Pharmacy
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center, Department of Pharmacy
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center,Sungkyunkwan Univ School of Medicine
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center/Division of Nephrology
city: Seoul
country: Korea, Republic of
facility: Boramae Medical Center/Division of Nephrology
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Kota Bharu
country: Malaysia
facility: Universiti Sains Malaysia
state: Kelantan
city: Kubang Kerian
country: Malaysia
facility: Unit Kajian Klinikal, Hospital Universiti Sains Malaysia
state: Kelantan
city: Taiping
country: Malaysia
facility: Hospital Taiping
state: Perak
city: George Town
country: Malaysia
facility: Clinical Research Centre, Hospital Pulau Pinang
state: Pulau Pinang
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
state: Pulau Pinang
city: Kota Kinabalu
country: Malaysia
facility: Nephrology Clinic, Queen Elizabeth Hospital
state: Sabah
city: Kajang
country: Malaysia
facility: Unit Hemodialisis, Hospital Serdang
state: Selangor
city: Mexico
country: Mexico
facility: Comite Mexicano para la Prevencion de la Osteoporosis, A.C.
state: DF
city: Guadalajara
country: Mexico
facility: ICLE SC
state: Jalisco
city: Tlalpan
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (INCMNSZ)
state: Mexico CITY
city: San Luis Potosi
country: Mexico
facility: Hospital Central Dr Ignacio Morones Prieto Unidad Regional de Osteoporosis
state: San Luis
city: Angeles Del Pedregal Cp.
country: Mexico
facility: Hospital Angeles del Pedregal
city: Bielsko-Biala
country: Poland
facility: NZOZ "DIAGNOMED" S.C., Poradnia Nefrologiczna
city: Katowice
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny im Andrzeja Mieleckiego
city: Lublin
country: Poland
facility: NZOZ PS "Medica"
city: Warsaw
country: Poland
facility: Miedzyleski Szpital Specjalistyczny w Warszawie
city: Warszawa
country: Poland
facility: Centrum Medyczne "Osteomed" NZOZ, Lecznica Specjalistow
city: Warszawa
country: Poland
facility: Centrum Medyczne "OSTEOMED" NZOZ
city: Warszawa
country: Poland
facility: Centrum Medyczne "Osteomed"
city: Warszawa
country: Poland
facility: Centrum Medyczne OSTEOMED NZOZ; Lecznica Specjalistaw
city: Wroclaw
country: Poland
facility: SPZOZ Akademicki Szpital Kliniczny im. J. Mikulicza - Radeckiego
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia Institute for Endocrinology, Diabetes and Metabolic Diseases
city: Belgrade
country: Serbia
facility: Clinic for Nephrology, Military Medical Academy
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical Hospital Center "Zvezdara"
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zvezdara
city: Nis
country: Serbia
facility: Clinic for Endocrinology, Clinical Center Nis
city: Bratislava
country: Slovakia
facility: FNsP Bratislava, Nemocnica Stare Mesto
city: Levice
country: Slovakia
facility: Nemocnice s poliklinikami n.o.
city: Presov
country: Slovakia
facility: Fakultna nemocnica s poliklinikou J.A.Reimana Presov
city: Rimavska Sobota
country: Slovakia
facility: Vseobecna nemocnica Rimavska Sobota
city: Johannesburg
country: South Africa
facility: Wits Clinical research
state: Gauteng- South Africa
city: Benoni
country: South Africa
facility: Worthwhile Clinical Trials (WWCT), Lake View Hospital
state: Gauteng
city: Pretoria
country: South Africa
facility: Dr. George Mukhari Hospital -University of Limpopo
state: Gauteng
city: Durban
country: South Africa
facility: Centre for Diabetes and Endocrinology
state: Kwazulu Natal
city: Bloemfontein
country: South Africa
facility: Latros International
city: Cape Town
country: South Africa
facility: Division of Nephrology and Hypertension, E13 Renal Unit
city: Durban
country: South Africa
facility: St Augustine's Hospital
city: Durban
country: South Africa
facility: Centre for Diabetes and Endocrinology
city: Houghton, Johannesburg
country: South Africa
facility: Centre for Diabetes and Endocrinology
city: Parow
country: South Africa
facility: Intercare Parow Medical and Dental Centre
city: Pretoria
country: South Africa
facility: Medi-Clinic Heart Hospital (Pretoria Heart Hospital)
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital Njurmottagningen
city: Stockholm
country: Sweden
facility: A+ Science City site
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: South Yorkshire
city: Coventry
country: United Kingdom
facility: Research Offices (5th Floor)
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh
city: London
country: United Kingdom
facility: The Royal London Hospital Whitechapel
city: London
country: United Kingdom
facility: Guy's and St Thomas' Foundation Trust
city: Sheffield
country: United Kingdom
facility: Northern General Hospital Campus
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: