A Phase 2, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of PF-00489791 In Patients With Type 2 Diabetes And Overt Nephropathy

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathies
• Intervention / Treatment: Drug: PF-00489791; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 256
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Gosford, New South Wales, Australia, 2250
      • Renal Research Practice
    • Newcastle, New South Wales, Australia, 2305
      • John Hunter Hospital
  • Newcastle
    • New Lambton, Newcastle, Australia, 2305
      • Department of Nephrology
    • New Lambton, Newcastle, Australia, 2305
      • Pharmacy Department
  • Victoria
    • Reservoir, Victoria, Australia, 3073
      • Melbourne Renal Research Group
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 0X7
      • Sheldon M Chumir Health Centre
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • Brampton, Ontario, Canada, L6Z 4N5
      • Entralogix Clincal Research Inc.
    • Brampton, Ontario, Canada, L6Z 4N5
      • Entralogix Clinical Research Inc.
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Oakville, Ontario, Canada, L6J 3M5
      • Entralogix Clinical Research Inc.
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Center
    • Toronto, Ontario, Canada, M4C 5T2
      • N/A - formerly with Entralogix SMO
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Centre de santé et de services sociaux Champlain-Charles-Le Moyne
    • Montreal, Quebec, Canada, H3M 3E3
      • Centre de Dialyse de Bois de Boulogne
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital de Sacre Coeur de Montreal
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7M 2Z1
      • Saskatoon Nephrology Group, Nurses Redisence
    • Saskatoon, Saskatchewan, Canada, S7M 2Z1
      • Saskatoon Nephrology Group, Nurses Residence
    • Saskatoon, Saskatchewan, Canada, S7M 2Z1
      • Saskatoon Nephrology Group
• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus Universitetshospital (Aarhus Sygehus)
  • Copenhagen Oe, Denmark, 2100
    • Rigshospitalet
  • Gentofte, Denmark, 2820
    • Steno Diabetes Center
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Pokfulam, Hong Kong
    • Division of Nephrology, Dept. of Medicine
  • Pokfulam, Hong Kong
    • Division of Nephrology
  • Quarry Bay, Hong Kong
    • ICON Clinical Research
  • Shatin, Hong Kong, N.T. 0
    • Prince of Wales Hospital
• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500096
      • Apollo Hospitals
  • Gujarat
    • Ahmedabad, Gujarat, India, 380 007
      • Gujarat Kidney Foundation
    • Ahmedabad, Gujarat, India, 380 013
      • Shrushrut Clinical Research Association
  • Maharashtra
    • Mumbai, Maharashtra, India, 400016
      • P. D. Hinduja National Hospital and Medical Research Centre
    • Mumbai, Maharashtra, India, 400102
      • Pfizer Centre
    • Pune, Maharashtra, India, 411001
      • Jehangir Clinical Development Centre Pvt. Ltd.
    • Pune, Maharashtra, India, 411 004
      • Deenanath Mangeshkar Hospital & Research Centre
    • Pune, Maharashtra, India, 411 011
      • Diabetes Care and Research Centre
    • Pune, Maharashtra, India, 411 011
      • KE.M Hospital Research Centre
    • Pune, Maharashtra, India, 411 011
      • King Edward Memorial Hospital
• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 463-707
    • Clinical trial Pharmacy
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 156-707
    • SMG-SNU Boramae Medical Center
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center/Division of Nephrology
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center, Department of Pharmacy
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center,Sungkyunkwan Univ School of Medicine
  • Seoul, Korea, Republic of, 156-707
    • Boramae Medical Center/Division of Nephrology
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Pharmacy
• Malaysia
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 16150
      • Universiti Sains Malaysia
    • Kubang Kerian, Kelantan, Malaysia, 16150,
      • Unit Kajian Klinikal, Hospital Universiti Sains Malaysia
  • Perak
    • Taiping, Perak, Malaysia, 34000
      • Hospital Taiping
  • Pulau Pinang
    • George Town, Pulau Pinang, Malaysia, 10990
      • Hospital Pulau Pinang
    • George Town, Pulau Pinang, Malaysia, 10990
      • Clinical Research Centre, Hospital Pulau Pinang
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Nephrology Clinic, Queen Elizabeth Hospital
  • Selangor
    • Kajang, Selangor, Malaysia, 43000
      • Unit Hemodialisis, Hospital Serdang
• Mexico
  • Angeles Del Pedregal Cp., Mexico, 10700
    • Hospital Ángeles del Pedregal
  • DF
    • Mexico, DF, Mexico, 06100
      • Comite Mexicano para la Prevencion de la Osteoporosis, A.C.
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44600
      • ICLE SC
  • Mexico CITY
    • Tlalpan, Mexico CITY, Mexico, 14000
      • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ)
  • San Luis
    • San Luis Potosi, San Luis, Mexico, 78240
      • Hospital Central Dr Ignacio Morones Prieto Unidad Regional de Osteoporosis
• Poland
  • Bielsko-Biala, Poland, 43-300
    • NZOZ "DIAGNOMED" S.C., Poradnia Nefrologiczna
  • Katowice, Poland, 40-027
    • Samodzielny Publiczny Szpital Kliniczny im Andrzeja Mieleckiego
  • Lublin, Poland, 20-538
    • NZOZ PS "Medica"
  • Warsaw, Poland, 4749
    • Międzyleski Szpital Specjalistyczny w Warszawie
  • Warszawa, Poland, 02-256
    • Centrum Medyczne "Osteomed" NZOZ, Lecznica Specjalistow
  • Warszawa, Poland, 02-256
    • Centrum Medyczne "OSTEOMED" NZOZ
  • Warszawa, Poland, 02-256
    • Centrum Medyczne "Osteomed"
  • Warszawa, Poland, 02-256
    • Centrum Medyczne OSTEOMED NZOZ; Lecznica Specjalistaw
  • Wroclaw, Poland, 50-556
    • SPZOZ Akademicki Szpital Kliniczny im. J. Mikulicza - Radeckiego
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Zvezdara
  • Belgrade, Serbia, 11 000
    • Clinical Center of Serbia Institute for Endocrinology, Diabetes and Metabolic Diseases
  • Belgrade, Serbia, 11000
    • Clinic for Nephrology, Military Medical Academy
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center "Zvezdara"
  • Nis, Serbia, 18000
    • Clinic for Endocrinology, Clinical Center Nis
• Slovakia
  • Bratislava, Slovakia, 813 69
    • FNsP Bratislava, Nemocnica Stare Mesto
  • Levice, Slovakia, 934 01
    • Nemocnice s poliklinikami n.o.
  • Presov, Slovakia, 081 81
    • Fakultna nemocnica s poliklinikou J.A.Reimana Presov
  • Rimavska Sobota, Slovakia, 979 12
    • Vseobecna nemocnica Rimavska Sobota
• South Africa
  • Bloemfontein, South Africa, 9301
    • Latros International
  • Cape Town, South Africa, 7925
    • Division of Nephrology and Hypertension, E13 Renal Unit
  • Durban, South Africa, 4001
    • St Augustine's Hospital
  • Durban, South Africa, 4091
    • Centre for Diabetes and Endocrinology
  • Houghton, Johannesburg, South Africa, 2198
    • Centre for Diabetes and Endocrinology
  • Parow, South Africa, 7500
    • Intercare Parow Medical and Dental Centre
  • Pretoria, South Africa, 132
    • Medi-Clinic Heart Hospital (Pretoria Heart Hospital)
  • Gauteng
    • Benoni, Gauteng, South Africa, 1500
      • Worthwhile Clinical Trials (WWCT), Lake View Hospital
    • Pretoria, Gauteng, South Africa, 0204
      • Dr. George Mukhari Hospital -University of Limpopo
  • Gauteng- South Africa
    • Johannesburg, Gauteng- South Africa, South Africa, 2096
      • Wits Clinical Research
  • Kwazulu Natal
    • Durban, Kwazulu Natal, South Africa, 4091
      • Centre for Diabetes and Endocrinology
• Sweden
  • Goteborg, Sweden, 413 45
    • Sahlgrenska University Hospital Njurmottagningen
  • Stockholm, Sweden, 111 57
    • A+ Science City site
  • Uppsala, Sweden, 751 85
    • Akademiska sjukhuset
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • Research Offices (5th Floor)
  • Edinburgh, United Kingdom, EH16 4TJ
    • University of Edinburgh
  • London, United Kingdom, E1 1BB
    • The Royal London Hospital Whitechapel
  • London, United Kingdom, SE1 9RT
    • Guy's and St Thomas' Foundation Trust
  • Sheffield, United Kingdom, S5 7AU
    • Northern General Hospital Campus
  • South Yorkshire
    • Doncaster, South Yorkshire, United Kingdom, DN2 5LT
      • Doncaster Royal Infirmary
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Saadat Ansari Internal Medicine
    • Huntsville, Alabama, United States, 35805
      • The Office of Iqbal Saeed MD, LLC
  • Arizona
    • Glendale, Arizona, United States, 85306
      • AKDHC Medical Research Services, LLC*
    • Tempe, Arizona, United States, 85284
      • Southwest Clinical Research Institute, LLC
    • Tempe, Arizona, United States, 85281
      • Southwest Clinical Research Institute, LLC
  • California
    • Azusa, California, United States, 91702
      • North America Research Institute
    • Azusa, California, United States, 91702
      • North American Research Institute / California Kidney Specialist
    • Covina, California, United States, 91723
      • Citrus Dialysis Center
    • La Mesa, California, United States, 91942
      • California Institute of Renal Research
    • Sacramento, California, United States, 95825
      • Capital Nephrology Clinical Research
    • San Dimas, California, United States, 91773
      • California Kidney Specialists
    • Whittier, California, United States, 90602
      • American Institute of Research
    • Whittier, California, United States, 90602
      • Whittier Internal Medicine Nephrology Medical Group
    • Yuba, California, United States, 95991
      • North Valley Nephrology
  • Florida
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research
    • Hialeah, Florida, United States, 33012
      • Palm Springs Research Institute
    • Jupiter, Florida, United States, 33458
      • ASA Clinical Research, LLC
    • Summerfield, Florida, United States, 34491
      • Lakeview Medical Research
  • Georgia
    • Conyers, Georgia, United States, 30094
      • Rockdale Medical Research Associates
    • Macon, Georgia, United States, 31217
      • Renal Physicians of Georgia
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Boise Kidney and Hypertension Institute
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Chicago Clinical Research Institute, Inc.
    • Evergreen Park, Illinois, United States, 60805
      • Research by Design, LLC
    • Evergreen Park, Illinois, United States, 60805
      • Associates in Nephrology, SC
    • Peoria, Illinois, United States, 61603
      • RenalCare Associates
  • Indiana
    • Elwood, Indiana, United States, 46036
      • Investigative Clinical Research of Indiana, LLC
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Kansas Nephrology Research Institute, LLC
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Inc.
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Crescent City Clinical Research Center
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Biolab Research, LLC
  • Michigan
    • Dearborn, Michigan, United States, 48124
      • Alzohaili Medical Consultants
    • Flint, Michigan, United States, 48504
      • Apex Medical Research, AMR, Inc.
    • Flint, Michigan, United States, 48504
      • Apex Medical Research, MI, Inc.
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Lincoln Nephrology and Hypertension
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Nephrology Research Institute, LLC - Research Management, Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clinical Research Consortium
    • Las Vegas, Nevada, United States, 89101
      • Alliance Against Diabetes
  • New York
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center - Department of Medicine - Nephrology
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates, PA
    • Wilmington, North Carolina, United States, 28401
      • Trial Management Associates
  • Ohio
    • Willoughby Hills, Ohio, United States, 44094
      • Lake Medical Research
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center, LLC
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians, Inc.
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology Associates, PA
    • Greenville, South Carolina, United States, 29605
      • Carolina Nephrology, PA
    • Orangeburg, South Carolina, United States, 29118
      • Palmetto Nephrology, PA
    • Orangeburg, South Carolina, United States, 29118
      • South Carolina Nephrology & Hypertension Ctr, Inc
    • Orangeburg, South Carolina, United States, 29118
      • South Carolina Nephrology and Hypertension Center
  • Texas
    • Austin, Texas, United States, 78751
      • Research Management, Inc.
    • Austin, Texas, United States, 78751
      • Central Texas Kidney Associates
    • Houston, Texas, United States, 77054
      • Research Across America
    • Houston, Texas, United States, 77004
      • Diagnostic Clinic of Houston, PA
    • Houston, Texas, United States, 77024
      • Houston Nephrology Research
    • San Antonio, Texas, United States, 78215
      • Renal Associates, PA
    • San Antonio, Texas, United States, 78229
      • San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
  • Virginia
    • Fairfax, Virginia, United States, 22033
      • Nephrology Associates of Northern Virginia, Inc.
    • Mechanicsville, Virginia, United States, 23116
      • Nephrology Specialists, P.C.
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater
  • Washington
    • Bremerton, Washington, United States, 98310
      • Renal Remission & Hypertension Consultants, PLLC
    • Port Orchard, Washington, United States, 98366
      • Sound Medical Research
    • Silverdale, Washington, United States, 98383
      • Renal Remission and Hypertension Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Tablet, placebo once daily for 12 weeks
Experimental: PF-00489791	Drug: PF-00489791; Tablet, 20 mg once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 12	UACR was ratio of albumin measured in urine (milligram) to creatinine measured in urine (millimole), reported in units milligram per millimole (mg/mmol). A decrease in UACR may be associated with improved renal and cardiovascular function. The mean values of the 3 consecutive first morning void urine samples (obtained 2 days prior to [Day 5, 6 of Week 12], and with last sample collected on the morning of scheduled clinic visit [Day 7 of Week 12]) were used to determine UACR at the scheduled clinic visit. The mean values of the 3 consecutive first morning void urine samples obtained at screening were used to determine baseline UACR.	Baseline, Week 12 (Day 5, 6, 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 3, 6 and 16	UACR was ratio of albumin measured in urine (milligram) to creatinine measured in urine (millimole), reported in units mg/mmol. A decrease in UACR may be associated with improved renal and cardiovascular function. The mean values of the 3 consecutive first morning void urine samples (obtained 2 days prior to [Day 5, 6 of specified Week], and with last sample collected on the morning of scheduled clinic visit [Day 7 of specified Week]) were used to determine UACR at the scheduled clinic visit. The mean values of the 3 consecutive first morning void urine samples obtained at screening were used to determine baseline UACR.	Baseline, Week 3 (Day 5, 6, 7), Week 6 (Day 5, 6, 7), Week 16 (Day 5, 6, 7)
Change From Baseline in Urinary Protein Creatinine Ratio (UPCR) at Week 3, 6, 12, and 16	UPCR is a ratio between two measured substances in urine: milligram of protein per millimole (mmol) of creatinine, reported in units mg/mmol. A decrease in UPCR may be associated with improved renal and cardiovascular function. The mean values of the 3 consecutive first morning void urine samples (obtained 2 days prior to [Day 5, 6 of Week 3, 6, 12, 16], and with last sample collected on the morning of scheduled clinic visit [Day 7 of Week 3, 6, 12, 16]) were used to determine UPCR at the scheduled clinic visit. The mean values of the 3 consecutive first morning void urine samples obtained at screening were used to determine baseline UPCR.	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)
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 3, 6, 12, and 16	The eGFR was calculated using 4 variable formula developed by the modification of diet in renal disease (MDRD) study group. The 4 variables needed to estimate glomerular filtration rate (GFR) using this formula were serum creatinine concentration (sCr), age, sex (for females, eGFR was multiplied by 0.742) and ethnic origin (for African-Caribbean people only, eGFR was multiplied by 1.212). Thus eGFR in milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) = 175*(sCr/88.4)^-1.154*(Age)^-0.203*(0.742 if female)*(1.212 if African-Caribbean). Baseline eGFR was determined predose at Week 0 (Day 1).	Baseline, Week 3, 6, 12, 16 (follow-up)
Systolic, Diastolic and Mean Blood Pressure at Week 0, 3, 6, 12, and 16	Systolic blood pressure (SBP) is the blood pressure (pressure exerted by circulating blood on the walls of blood vessels) when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle of heart. diastolic blood pressure (DBP) is the blood pressure (pressure exerted by circulating blood on the walls of blood vessels) when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles of heart. Mean blood pressure (MBP) = diastolic blood pressure + ([systolic blood pressure - diastolic blood pressure]/3). After a minimum of 5 minutes of rest, supine BP was measured with the participant's arm supported at the level of the heart.	Week 0, 3, 6, 12, 16 (follow-up)
Change From Baseline in Serum Creatinine Concentration at Week 3, 6, 12, and 16	Serum creatinine concentration was used as a marker of renal function. Baseline serum creatinine concentration was determined predose at Week 0 (Day 1).	Baseline, Week 3, 6, 12, 16 (follow-up)
Change From Baseline in Urine Transforming Growth Factor (TGF) Beta-1 Concentration at Week 3, 6, 12, and 16	TGF Beta-1 is a major fibrogenic growth factor implicated in the pathogenesis of renal scarring. It is overexpressed in the diabetic kidney where it may promote matrix accumulation. Baseline TGF Beta-1 concentration was determined predose at Week 0 (Day 1).	Baseline, Week 3, 6, 12, 16 (follow-up)
Change From Baseline in Serum High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 12 and 16	The CRP is an acute phase reactant which is virtually absent from the blood serum of healthy persons but rapidly appears in blood and body fluids in response to injurious stimuli. Baseline hs-CRP was determined predose at Week 0 (Day 1).	Baseline, Week 12, 16 (follow-up)
Change From Baseline in Serum Cystatin-C Concentration at Week 12 and 16	Cystatin C is produced by all nucleated cells at a constant rate and is freely filtered at the glomerulus. The blood concentration of cystatin C depends almost entirely on the GFR and is not substantially affected by diet, nutritional status or inflammatory disease. Serum cystatin C had been proposed as an endogenous marker of GFR in participant with chronic kidney disease (CKD) than sCr. Baseline serum cystatin C was determined predose at Week 0 (Day 1).	Baseline, Week 12, 16 (follow-up)
Plasma Concentration Versus Time Summary of PF-00489791		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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) Level at Week 12 and 16	Level of HbA1c is an indicator for the average level of blood glucose over the previous 3 months. Baseline HbA1c level was determined predose at Week 0 (Day 1).	Baseline, Week 12, 16 (follow-up)
Number of Participants With Vital Signs Abnormalities	Criteria for determining vital signs abnormalities: supine or standing systolic BP (SBP) (less than [<] 90 mmHg and increase or decrease of greater than or equal to [>=] 30 mmHg compared to baseline value), supine or standing diastolic BP (DBP) (<50 mmHg and increase or decrease of >=20 mmHg compared to baseline value), supine pulse rate (>120 beats per minute [bpm] or <40 bpm), standing pulse rate (>140 bpm or <40 bpm). For supine, baseline was the average of the triplicate predose readings at Week 0 (Day 1). For standing, baseline is the predose reading at Week 0 (Day 1). Only categories who had at least 1 participant are reported.	Baseline up to Week 16 (follow-up)
Number of Participants With Edema and Fluid Overload	Participants were assessed for signs of edema and fluid overload.	Week 0, 3, 6, 12, 16 (follow-up)
Number of Participants With Increased Use of Diuretics		Baseline up to Week 16 (follow-up)
Number of Participants With Laboratory Test Abnormalities	Criteria for laboratory test abnormalities: Hematology (hemoglobin [<0.8*lower limit of normal{LLN}], hematocrit [<0.8*LLN], red blood cells [<0.8*LLN], platelet [<0.5*LLN/>1.75*upper limit of normal{ULN}], white blood cells [<0.6*LLN/>1.5*ULN], lymphocytes [<0.8*LLN/>1.2*ULN], neutrophils [<0.8*LLN/>1.2*ULN], basophils [>1.2*ULN], eosinophils [>1.2*ULN], monocytes [>1.2*ULN]); Liver Function (total/direct/indirect bilirubin [>1.5*ULN], aspartate aminotransferase/ alanine aminotransferase/ gamma glutamyl transpeptidase/ lactate dehydrogenase/ alkaline phosphatase [>3.0*ULN]); Renal Function (blood urea nitrogen/ creatinine [>1.3*ULN], uric acid [>1.2*ULN]); Electrolytes (sodium [<0.95*LLN/>1.05*ULN], potassium, chloride, calcium, bicarbonate [<0.9*LLN/>1.1*ULN]); Clinical Chemistry (glucose [<0.6*LLN/>1.5*ULN], glycosylated hemoglobin [>1.3*ULN], Creatine Kinase [>2.0*ULN], Amylase, Lipase[>1.5*ULN]).	Baseline up to Week 16 (follow-up)
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication and up to Week 16 (follow-up) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both non-serious (AEs) and serious adverse events (SAEs)	Baseline up to Week 16 (follow-up)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2010
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: September 10, 2010
• First Submitted That Met QC Criteria: September 10, 2010
• First Posted (Estimate): September 13, 2010

Study Record Updates

• Last Update Posted (Actual): March 12, 2019
• Last Update Submitted That Met QC Criteria: February 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: chronic kidney disease; Diabetic nephropathy; PF-00489791; phosphodiesterase; PDE5
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: A7331011; 2010-021358-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.