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

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01200394
Collaborator
(none)
256
Enrollment
160
Locations
2
Arms
32
Actual Duration (Months)
1.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
256 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 1, 2010
Actual Primary Completion Date :
Jul 1, 2013
Actual Study Completion Date :
Aug 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: PF-00489791

Drug: PF-00489791
Tablet, 20 mg once daily for 12 weeks
Placebo Comparator: Placebo

Drug: Placebo
Tablet, placebo once daily for 12 weeks

Outcome Measures

Primary Outcome Measures

  1. Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 12 [Baseline, Week 12 (Day 5, 6, 7)]

    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.

Secondary Outcome Measures

  1. Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 3, 6 and 16 [Baseline, Week 3 (Day 5, 6, 7), Week 6 (Day 5, 6, 7), Week 16 (Day 5, 6, 7)]

    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.

  2. Change From Baseline in Urinary Protein Creatinine Ratio (UPCR) at Week 3, 6, 12, and 16 [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)]

    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.

  3. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 3, 6, 12, and 16 [Baseline, Week 3, 6, 12, 16 (follow-up)]

    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).

  4. Systolic, Diastolic and Mean Blood Pressure at Week 0, 3, 6, 12, and 16 [Week 0, 3, 6, 12, 16 (follow-up)]

    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.

  5. Change From Baseline in Serum Creatinine Concentration at Week 3, 6, 12, and 16 [Baseline, Week 3, 6, 12, 16 (follow-up)]

    Serum creatinine concentration was used as a marker of renal function. Baseline serum creatinine concentration was determined predose at Week 0 (Day 1).

  6. Change From Baseline in Urine Transforming Growth Factor (TGF) Beta-1 Concentration at Week 3, 6, 12, and 16 [Baseline, Week 3, 6, 12, 16 (follow-up)]

    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).

  7. Change From Baseline in Serum High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 12 and 16 [Baseline, Week 12, 16 (follow-up)]

    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).

  8. Change From Baseline in Serum Cystatin-C Concentration at Week 12 and 16 [Baseline, Week 12, 16 (follow-up)]

    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).

  9. 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

  1. Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) Level at Week 12 and 16 [Baseline, Week 12, 16 (follow-up)]

    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).

  2. Number of Participants With Vital Signs Abnormalities [Baseline up to Week 16 (follow-up)]

    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.

  3. Number of Participants With Edema and Fluid Overload [Week 0, 3, 6, 12, 16 (follow-up)]

    Participants were assessed for signs of edema and fluid overload.

  4. Number of Participants With Increased Use of Diuretics [Baseline up to Week 16 (follow-up)]

  5. Number of Participants With Laboratory Test Abnormalities [Baseline up to Week 16 (follow-up)]

    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]).

  6. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to Week 16 (follow-up)]

    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)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

  • Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01200394
Other Study ID Numbers:
  • A7331011
  • 2010-021358-20
First Posted:
Sep 13, 2010
Last Update Posted:
Mar 12, 2019
Last Verified:
Feb 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Pfizer
Diabetic nephropathy
chronic kidney disease
PF-00489791
phosphodiesterase
PDE5
Additional relevant MeSH terms:
Kidney Diseases
Diabetic Nephropathies

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Period Title: Overall Study
STARTED 64 192
COMPLETED 62 164
NOT COMPLETED 2 28

Baseline Characteristics

Arm/Group Title Placebo PF-00489791 20 mg Total
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks. Total of all reporting groups
Overall Participants 64 192 256
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
59.8
(11.0)
62.0
(8.8)
61.5
(9.4)
Sex: Female, Male (Count of Participants)
Female
13
20.3%
48
25%
61
23.8%
Male
51
79.7%
144
75%
195
76.2%
Race/Ethnicity, Customized (participants) [Number]
White
27
42.2%
79
41.1%
106
41.4%
Black
5
7.8%
13
6.8%
18
7%
Asian
26
40.6%
83
43.2%
109
42.6%
Other
6
9.4%
17
8.9%
23
9%

Outcome Measures

1. Primary Outcome
Title Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 12
Description 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.
Time Frame Baseline, Week 12 (Day 5, 6, 7)

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose efficacy measurement. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Baseline
195.130
(171.8116)
182.378
(156.5097)
Change at Week 12
9.072
(176.4360)
-6.539
(128.4866)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Analysis of covariance (ANCOVA) model within an outlier robust Bayesian framework on normal logarithmic scale with treatment as fixed effect, baseline UACR and baseline supine systolic blood pressure (BP) as covariate. Values were back-transformed from log scale. Model used informative prior distribution for placebo.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.9889
Comments Posterior distribution was used to calculate a probability (presented as P-value) that PF-00489791 has a greater than 0% reduction in UACR compared to placebo.
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.843
Confidence Interval (2-Sided) 95%
0.728 to 0.975
Parameter Dispersion Type:
Value:
Estimation Comments Geometric mean ratio and corresponding 95% credible intervals were calculated.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments ANCOVA model within an outlier robust Bayesian framework on normal logarithmic scale with treatment as fixed effect, baseline UACR and baseline supine systolic BP as covariate. Values were back-transformed from log scale. Model used informative prior distribution for placebo.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.2402
Comments Posterior distribution was used to calculate a probability (presented as P-value) that PF-00489791 has a greater than or equal to 20% reduction in UACR compared to placebo.
Method ANCOVA
Comments
2. Secondary Outcome
Title Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 3, 6 and 16
Description 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.
Time Frame Baseline, Week 3 (Day 5, 6, 7), Week 6 (Day 5, 6, 7), Week 16 (Day 5, 6, 7)

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose efficacy measurement. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Change at Week 3
-11.805
(161.7282)
-14.268
(94.8469)
Change at Week 6
-7.772
(162.0838)
-2.546
(179.5896)
Change at Week 16
16.500
(202.7600)
2.802
(107.9582)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 3: Mixed model repeated measures (MMRM) on normal logarithmic scale with baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0382
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.8759
Confidence Interval (2-Sided) 95%
0.7727 to 0.9927
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 6: MMRM on normal logarithmic scale with baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0112
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.8311
Confidence Interval (2-Sided) 95%
0.7208 to 0.9584
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 16: MMRM on normal logarithmic scale with baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.1490
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.8816
Confidence Interval (2-Sided) 95%
0.7427 to 1.0465
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Change From Baseline in Urinary Protein Creatinine Ratio (UPCR) at Week 3, 6, 12, and 16
Description 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.
Time Frame 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)

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose efficacy measurement. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Baseline
282.208
(259.8496)
261.015
(220.5260)
Change at Week 3
-20.302
(247.4490)
-26.883
(161.0038)
Change at Week 6
-10.278
(256.7216)
10.699
(290.5749)
Change at Week 12
14.632
(283.9874)
-5.371
(207.3333)
Change at Week 16
30.880
(332.0766)
20.299
(190.3546)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 3: MMRM on normal logarithmic scale with baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0297
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.8565
Confidence Interval (2-Sided) 95%
0.7450 to 0.9847
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 6: MMRM on normal logarithmic scale with baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0305
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.8524
Confidence Interval (2-Sided) 95%
0.7376 to 0.9850
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 12: MMRM on normal logarithmic scale with baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0068
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.7937
Confidence Interval (2-Sided) 95%
0.6717 to 0.9378
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 16: MMRM on normal logarithmic scale with baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.1151
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.8634
Confidence Interval (2-Sided) 95%
0.7190 to 1.0368
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 3, 6, 12, and 16
Description 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).
Time Frame Baseline, Week 3, 6, 12, 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose efficacy measurement. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Baseline
38.575
(11.9122)
37.740
(9.8834)
Change at Week 3
0.069
(6.2868)
-0.156
(4.6044)
Change at Week 6
-0.930
(5.3513)
-0.755
(5.2701)
Change at Week 12
-1.435
(5.3757)
-1.463
(5.1074)
Change at Week 16
-1.915
(5.9005)
-1.659
(6.0659)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 3: MMRM on normal logarithmic scale with change from baseline as response variable and baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.3585
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.9816
Confidence Interval (2-Sided) 95%
0.9434 to 1.0214
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 6: MMRM on normal logarithmic scale with change from baseline as response variable and baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.7475
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.9939
Confidence Interval (2-Sided) 95%
0.9577 to 1.0315
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 12: MMRM on normal logarithmic scale with change from baseline as response variable and baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.4972
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.9866
Confidence Interval (2-Sided) 95%
0.9488 to 1.0259
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 16: MMRM on normal logarithmic scale with change from baseline as response variable and baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.9146
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.0024
Confidence Interval (2-Sided) 95%
0.9588 to 1.0481
Parameter Dispersion Type:
Value:
Estimation Comments
5. Secondary Outcome
Title Systolic, Diastolic and Mean Blood Pressure at Week 0, 3, 6, 12, and 16
Description 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.
Time Frame Week 0, 3, 6, 12, 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose efficacy measurement.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Supine Systolic BP, Week 0
137.20
131.81
Supine Diastolic BP, Week 0
76.98
73.27
Supine Mean BP, Week 0
107.27
102.68
Supine Systolic BP, Week 3
136.68
136.15
Supine Diastolic BP, Week 3
76.78
77.18
Supine Mean BP, Week 3
107.06
106.90
Supine Systolic BP, Week 6
137.41
136.94
Supine Diastolic BP, Week 6
76.88
76.41
Supine Mean BP, Week 6
107.37
106.70
Supine Systolic BP, Week 12
136.89
137.70
Supine Diastolic BP, Week 12
77.32
76.69
Supine Mean BP, Week 12
107.41
107.14
Supine Systolic BP, Week 16
138.38
138.89
Supine Diastolic BP, Week 16
77.25
77.90
Supine Mean BP, Week 16
108.00
108.47
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Systolic BP, Week 0: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value -5.39
Confidence Interval (2-Sided) 95%
-7.94 to -2.84
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.2942
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Diastolic BP, Week 0: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.71
Confidence Interval (2-Sided) 95%
-5.38 to -2.04
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.8490
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Mean BP, Week 0: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.59
Confidence Interval (2-Sided) 95%
-6.46 to -2.72
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.9489
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Systolic BP, Week 3: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.7093
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-3.29 to 2.24
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.4056
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Diastolic BP, Week 3: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.6564
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
-1.39 to 2.20
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.9089
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Mean BP, Week 3: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.8763
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-2.20 to 1.87
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.0334
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Systolic BP, Week 6: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.7491
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-3.42 to 2.46
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.4926
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Diastolic BP, Week 6: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.6141
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-2.29 to 1.35
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.9235
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Mean BP, Week 6: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.5281
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.67
Confidence Interval (2-Sided) 95%
-2.75 to 1.42
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.0582
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Systolic BP, Week 12: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.6695
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
-2.90 to 4.50
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.8764
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Diastolic BP, Week 12: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.5607
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-2.74 to 1.49
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.0730
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Mean BP, Week 12: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.8297
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-2.78 to 2.23
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.2722
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Systolic BP, Week 16: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.7644
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
-2.85 to 3.87
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.7065
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Diastolic BP, Week 16: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.5123
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
-1.30 to 2.61
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.9917
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Supine Mean BP, Week 16: MMRM model included baseline, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. The unstructured covariance matrix was used to estimate variances and covariance within participant across time points.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.6838
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
-1.77 to 2.70
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.1355
Estimation Comments
6. Secondary Outcome
Title Change From Baseline in Serum Creatinine Concentration at Week 3, 6, 12, and 16
Description Serum creatinine concentration was used as a marker of renal function. Baseline serum creatinine concentration was determined predose at Week 0 (Day 1).
Time Frame Baseline, Week 3, 6, 12, 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose efficacy measurement. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Baseline
164.929
(42.0837)
163.637
(42.9529)
Change at Week 3
1.232
(23.9961)
2.691
(20.6884)
Change at Week 6
3.158
(18.0835)
4.974
(21.7977)
Change at Week 12
6.139
(20.7198)
8.110
(22.3709)
Change at Week 16
11.527
(28.5175)
9.269
(26.6470)
7. Secondary Outcome
Title Change From Baseline in Urine Transforming Growth Factor (TGF) Beta-1 Concentration at Week 3, 6, 12, and 16
Description 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).
Time Frame Baseline, Week 3, 6, 12, 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose efficacy measurement. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Baseline
177.88
(231.154)
213.37
(274.409)
Change at Week 3
-22.81
(260.140)
-54.06
(349.817)
Change at Week 6
23.33
(345.304)
-68.59
(333.378)
Change at Week 12
-36.20
(281.523)
-11.87
(328.482)
Change at Week 16
-23.54
(134.752)
-31.32
(299.546)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 3: MMRM on normal logarithmic scale with change from baseline as response variable and baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.5422
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.9282
Confidence Interval (2-Sided) 95%
0.7297 to 1.1807
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 6: MMRM on normal logarithmic scale with change from baseline as response variable and baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0490
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.7998
Confidence Interval (2-Sided) 95%
0.6402 to 0.9990
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 12: MMRM on normal logarithmic scale with change from baseline as response variable and baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.7264
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.0435
Confidence Interval (2-Sided) 95%
0.8211 to 1.3262
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
Comments Week 16: MMRM on normal logarithmic scale with change from baseline as response variable and baseline, baseline supine systolic BP, visit, treatment, baseline by visit interaction and treatment by visit interaction as fixed effects. Unstructured covariance matrix was used to estimate variances and covariance within participant across time points. Values were back-transformed from log scale.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.3733
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.1154
Confidence Interval (2-Sided) 95%
0.8761 to 1.4201
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title Change From Baseline in Serum High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 12 and 16
Description 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).
Time Frame Baseline, Week 12, 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose efficacy measurement. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Baseline
3.019
(3.4924)
4.330
(8.6809)
Change at Week 12
1.183
(3.4600)
0.106
(7.4909)
Change at Week 16
0.317
(2.9508)
-0.102
(6.3317)
9. Secondary Outcome
Title Change From Baseline in Serum Cystatin-C Concentration at Week 12 and 16
Description 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).
Time Frame Baseline, Week 12, 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Full analysis set included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose efficacy measurement. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Baseline
1.659
(0.4122)
1.695
(0.4497)
Change at Week 12
0.096
(0.1844)
0.070
(0.2890)
Change at Week 16
0.104
(0.3234)
0.075
(0.3176)
10. Secondary Outcome
Title Plasma Concentration Versus Time Summary of PF-00489791
Description
Time Frame 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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic analysis set included all randomized and treated participants with at least 1 measured PF-00489791 concentration. Here, "Number analyzed" signifies number of participants evaluable for specified categories. This outcome measure was planned not to be analyzed for Placebo reporting arm.
Arm/Group Title PF-00489791 20 mg
Arm/Group Description PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 191
4 hours post-dose at Day 1 of Week 0
0.6540
(0.33644)
Pre-dose at Day 1 of Week 3
0.4156
(0.44674)
4 hours post-dose at Day 1 of Week 3
0.9772
(0.59610)
Pre-dose at Day 1 of Week 6
0.3514
(0.40417)
4 hours post-dose at Day 1 of Week 6
0.9274
(0.52405)
Pre-dose at Day 1 of Week 12
0.3930
(0.41593)
11. Other Pre-specified Outcome
Title Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) Level at Week 12 and 16
Description 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).
Time Frame Baseline, Week 12, 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Safety analysis set consists of all participants who received at least 1 dose of study medication. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Baseline
7.13
(1.023)
7.39
(1.135)
Change at Week 12
0.12
(0.856)
-0.28
(0.975)
Change at Week 16
0.14
(1.009)
-0.09
(0.986)
12. Other Pre-specified Outcome
Title Number of Participants With Vital Signs Abnormalities
Description 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.
Time Frame Baseline up to Week 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Safety analysis set consists of all participants who received at least 1 dose of study medication. Here, 'Number analyzed' = Participants evaluable at specified time points for each arm, respectively.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Supine SBP <90 mmHg
0
0%
1
0.5%
Standing SBP <90 mmHg
0
0%
2
1%
Supine DBP <50 mmHg
0
0%
3
1.6%
Standing DBP <50 mmHg
0
0%
3
1.6%
Supine Pulse Rate <40 bpm
0
0%
1
0.5%
Increase in Supine SBP >=30 mmHg
0
0%
14
7.3%
Increase in Standing SBP >=30 mmHg
1
1.6%
1
0.5%
Increase in Supine DBP >=20 mmHg
0
0%
7
3.6%
Increase in Standing DBP >=20 mmHg
1
1.6%
0
0%
Decrease in Supine SBP >=30 mmHg
0
0%
9
4.7%
Decrease in Standing SBP >=30 mmHg
2
3.1%
11
5.7%
Decrease in Supine DBP >=20 mmHg
0
0%
5
2.6%
Decrease in Standing DBP >=20 mmHg
1
1.6%
11
5.7%
13. Other Pre-specified Outcome
Title Number of Participants With Edema and Fluid Overload
Description Participants were assessed for signs of edema and fluid overload.
Time Frame Week 0, 3, 6, 12, 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Safety analysis set consists of all participants who received at least 1 dose of study medication.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Week 0
0
0%
4
2.1%
Week 3
1
1.6%
8
4.2%
Week 6
1
1.6%
11
5.7%
Week 12
4
6.3%
9
4.7%
Week 16
5
7.8%
6
3.1%
14. Other Pre-specified Outcome
Title Number of Participants With Increased Use of Diuretics
Description
Time Frame Baseline up to Week 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Safety analysis set consists of all participants who received at least 1 dose of study medication.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
Count of Participants [Participants]
3
4.7%
10
5.2%
15. Other Pre-specified Outcome
Title Number of Participants With Laboratory Test Abnormalities
Description 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]).
Time Frame Baseline up to Week 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Safety analysis set consists of all participants who received at least 1 dose of study medication. Here 'N' (Overall Number of Participants Analyzed) signifies participants evaluable for this measure.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 63 190
Count of Participants [Participants]
62
96.9%
190
99%
16. Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description 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)
Time Frame Baseline up to Week 16 (follow-up)

Outcome Measure Data

Analysis Population Description
Safety analysis set consists of all participants who received at least 1 dose of study medication.
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
Measure Participants 64 192
AEs
36
56.3%
105
54.7%
SAEs
6
9.4%
13
6.8%

Adverse Events

Time Frame Baseline up to Week 16 (follow-up)
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. AEs included both non-serious (AEs) and serious adverse events (SAEs)
Arm/Group Title Placebo PF-00489791 20 mg
Arm/Group Description Placebo matched to PF-00489791 tablet orally once daily for 12 weeks. PF-00489791 20 milligram (mg) tablet orally once daily for 12 weeks.
All Cause Mortality
Placebo PF-00489791 20 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/64 (1.6%) 0/192 (0%)
Serious Adverse Events
Placebo PF-00489791 20 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 6/64 (9.4%) 13/192 (6.8%)
Blood and lymphatic system disorders
Anaemia 1/64 (1.6%) 3/192 (1.6%)
Haemorrhagic anaemia 0/64 (0%) 1/192 (0.5%)
Cardiac disorders
Acute myocardial infarction 1/64 (1.6%) 0/192 (0%)
Cardiac failure 0/64 (0%) 1/192 (0.5%)
Cardiac failure congestive 0/64 (0%) 2/192 (1%)
Coronary artery disease 0/64 (0%) 1/192 (0.5%)
Gastrointestinal disorders
Gastrointestinal haemorrhage 0/64 (0%) 1/192 (0.5%)
Melaena 0/64 (0%) 1/192 (0.5%)
Oesophagitis 0/64 (0%) 1/192 (0.5%)
Pancreatitis 0/64 (0%) 1/192 (0.5%)
General disorders
Chest discomfort 0/64 (0%) 1/192 (0.5%)
Infections and infestations
Cellulitis 1/64 (1.6%) 0/192 (0%)
Localised infection 0/64 (0%) 1/192 (0.5%)
Pneumonia 0/64 (0%) 1/192 (0.5%)
Injury, poisoning and procedural complications
Procedural hypotension 1/64 (1.6%) 0/192 (0%)
Metabolism and nutrition disorders
Hypoglycaemia 1/64 (1.6%) 0/192 (0%)
Musculoskeletal and connective tissue disorders
Gouty arthritis 1/64 (1.6%) 0/192 (0%)
Nervous system disorders
Cerebrovascular accident 0/64 (0%) 2/192 (1%)
Hemiparesis 0/64 (0%) 1/192 (0.5%)
Renal and urinary disorders
Renal failure 0/64 (0%) 1/192 (0.5%)
Renal failure acute 1/64 (1.6%) 1/192 (0.5%)
Reproductive system and breast disorders
Prostatitis 1/64 (1.6%) 0/192 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 0/64 (0%) 1/192 (0.5%)
Pulmonary embolism 0/64 (0%) 1/192 (0.5%)
Pulmonary oedema 0/64 (0%) 1/192 (0.5%)
Respiratory failure 1/64 (1.6%) 0/192 (0%)
Surgical and medical procedures
Prostatectomy 1/64 (1.6%) 0/192 (0%)
Vascular disorders
Accelerated hypertension 0/64 (0%) 1/192 (0.5%)
Other (Not Including Serious) Adverse Events
Placebo PF-00489791 20 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 35/64 (54.7%) 104/192 (54.2%)
Blood and lymphatic system disorders
Anaemia 0/64 (0%) 4/192 (2.1%)
Iron deficiency anaemia 0/64 (0%) 2/192 (1%)
Neutrophilia 0/64 (0%) 1/192 (0.5%)
Cardiac disorders
Cardiac failure 1/64 (1.6%) 1/192 (0.5%)
Coronary artery disease 1/64 (1.6%) 1/192 (0.5%)
Mitral valve incompetence 0/64 (0%) 1/192 (0.5%)
Palpitations 0/64 (0%) 2/192 (1%)
Ear and labyrinth disorders
Ear haemorrhage 0/64 (0%) 1/192 (0.5%)
Endocrine disorders
Autoimmune thyroiditis 0/64 (0%) 1/192 (0.5%)
Eye disorders
Diabetic retinopathy 0/64 (0%) 1/192 (0.5%)
Eye irritation 0/64 (0%) 2/192 (1%)
Lacrimation increased 0/64 (0%) 1/192 (0.5%)
Visual acuity reduced 0/64 (0%) 1/192 (0.5%)
Visual impairment 0/64 (0%) 2/192 (1%)
Gastrointestinal disorders
Abdominal discomfort 1/64 (1.6%) 0/192 (0%)
Abdominal distension 0/64 (0%) 1/192 (0.5%)
Colitis 1/64 (1.6%) 0/192 (0%)
Constipation 2/64 (3.1%) 2/192 (1%)
Diarrhoea 2/64 (3.1%) 17/192 (8.9%)
Dry mouth 1/64 (1.6%) 0/192 (0%)
Dyspepsia 1/64 (1.6%) 12/192 (6.3%)
Flatulence 0/64 (0%) 1/192 (0.5%)
Frequent bowel movements 0/64 (0%) 2/192 (1%)
Gastritis 0/64 (0%) 3/192 (1.6%)
Gastritis erosive 0/64 (0%) 1/192 (0.5%)
Gastroduodenitis 0/64 (0%) 1/192 (0.5%)
Gastrointestinal haemorrhage 1/64 (1.6%) 0/192 (0%)
Gastrooesophageal reflux disease 0/64 (0%) 4/192 (2.1%)
Irritable bowel syndrome 0/64 (0%) 1/192 (0.5%)
Large intestine polyp 0/64 (0%) 1/192 (0.5%)
Nausea 2/64 (3.1%) 4/192 (2.1%)
Oesophageal ulcer 0/64 (0%) 1/192 (0.5%)
Vomiting 2/64 (3.1%) 7/192 (3.6%)
General disorders
Chest discomfort 0/64 (0%) 1/192 (0.5%)
Chest pain 0/64 (0%) 2/192 (1%)
Chills 0/64 (0%) 1/192 (0.5%)
Face oedema 0/64 (0%) 1/192 (0.5%)
Fatigue 1/64 (1.6%) 2/192 (1%)
Feeling hot 0/64 (0%) 1/192 (0.5%)
Oedema 1/64 (1.6%) 3/192 (1.6%)
Oedema peripheral 6/64 (9.4%) 10/192 (5.2%)
Pyrexia 0/64 (0%) 4/192 (2.1%)
Peripheral swelling 0/64 (0%) 2/192 (1%)
Immune system disorders
Drug hypersensitivity 0/64 (0%) 1/192 (0.5%)
Hypersensitivity 0/64 (0%) 1/192 (0.5%)
Infections and infestations
Conjunctivitis 0/64 (0%) 1/192 (0.5%)
Abscess limb 0/64 (0%) 1/192 (0.5%)
Bronchitis 2/64 (3.1%) 1/192 (0.5%)
Cellulitis 0/64 (0%) 1/192 (0.5%)
Eye infection bacterial 0/64 (0%) 1/192 (0.5%)
Gastroenteritis 0/64 (0%) 1/192 (0.5%)
Influenza 0/64 (0%) 3/192 (1.6%)
Laryngitis 1/64 (1.6%) 0/192 (0%)
Lower respiratory tract infection 0/64 (0%) 1/192 (0.5%)
Mastitis fungal 0/64 (0%) 1/192 (0.5%)
Nasopharyngitis 1/64 (1.6%) 9/192 (4.7%)
Onychomycosis 1/64 (1.6%) 0/192 (0%)
Pharyngitis 0/64 (0%) 2/192 (1%)
Pneumonia 0/64 (0%) 1/192 (0.5%)
Respiratory tract infection 0/64 (0%) 1/192 (0.5%)
Rhinitis 0/64 (0%) 1/192 (0.5%)
Sinusitis 0/64 (0%) 1/192 (0.5%)
Tooth infection 1/64 (1.6%) 0/192 (0%)
Upper respiratory tract infection 1/64 (1.6%) 6/192 (3.1%)
Urinary tract infection 1/64 (1.6%) 0/192 (0%)
Injury, poisoning and procedural complications
Contusion 1/64 (1.6%) 0/192 (0%)
Fall 0/64 (0%) 1/192 (0.5%)
Humerus fracture 0/64 (0%) 1/192 (0.5%)
Laceration 0/64 (0%) 1/192 (0.5%)
Ligament sprain 0/64 (0%) 1/192 (0.5%)
Lip injury 1/64 (1.6%) 0/192 (0%)
Procedural pain 1/64 (1.6%) 0/192 (0%)
Spinal compression fracture 0/64 (0%) 1/192 (0.5%)
Skin abrasion 1/64 (1.6%) 1/192 (0.5%)
Investigations
Amylase increased 1/64 (1.6%) 1/192 (0.5%)
Blood calcium decreased 0/64 (0%) 1/192 (0.5%)
Blood creatine phosphokinase increased 3/64 (4.7%) 6/192 (3.1%)
Blood creatinine increased 1/64 (1.6%) 1/192 (0.5%)
Blood glucose abnormal 1/64 (1.6%) 0/192 (0%)
Blood glucose increased 1/64 (1.6%) 1/192 (0.5%)
Blood lactate dehydrogenase increased 1/64 (1.6%) 0/192 (0%)
Blood potassium increased 0/64 (0%) 3/192 (1.6%)
Blood pressure abnormal 0/64 (0%) 1/192 (0.5%)
Blood pressure increased 0/64 (0%) 1/192 (0.5%)
Blood urea increased 0/64 (0%) 2/192 (1%)
Blood uric acid increased 2/64 (3.1%) 0/192 (0%)
Electrocardiogram ST segment depression 0/64 (0%) 1/192 (0.5%)
Gamma-glutamyltransferase increased 1/64 (1.6%) 0/192 (0%)
Glycosylated haemoglobin increased 0/64 (0%) 1/192 (0.5%)
Haemoglobin decreased 1/64 (1.6%) 0/192 (0%)
International normalised ratio increased 0/64 (0%) 1/192 (0.5%)
Lipase increased 0/64 (0%) 2/192 (1%)
Liver function test normal 0/64 (0%) 1/192 (0.5%)
Weight decreased 0/64 (0%) 1/192 (0.5%)
Weight increased 0/64 (0%) 1/192 (0.5%)
Metabolism and nutrition disorders
Decreased appetite 0/64 (0%) 1/192 (0.5%)
Gout 0/64 (0%) 2/192 (1%)
Hyperamylasaemia 1/64 (1.6%) 0/192 (0%)
Hyperglycaemia 1/64 (1.6%) 4/192 (2.1%)
Hyperkalaemia 1/64 (1.6%) 2/192 (1%)
Hyperuricaemia 1/64 (1.6%) 3/192 (1.6%)
Hypoglycaemia 1/64 (1.6%) 1/192 (0.5%)
Hyponatraemia 1/64 (1.6%) 0/192 (0%)
Vitamin D deficiency 0/64 (0%) 1/192 (0.5%)
Musculoskeletal and connective tissue disorders
Arthralgia 1/64 (1.6%) 3/192 (1.6%)
Arthritis 0/64 (0%) 1/192 (0.5%)
Back pain 2/64 (3.1%) 5/192 (2.6%)
Joint swelling 0/64 (0%) 2/192 (1%)
Muscle spasms 2/64 (3.1%) 1/192 (0.5%)
Musculoskeletal pain 1/64 (1.6%) 0/192 (0%)
Myalgia 0/64 (0%) 2/192 (1%)
Neck pain 0/64 (0%) 1/192 (0.5%)
Osteoarthritis 0/64 (0%) 1/192 (0.5%)
Osteopenia 1/64 (1.6%) 0/192 (0%)
Pain in extremity 0/64 (0%) 3/192 (1.6%)
Spinal osteoarthritis 0/64 (0%) 1/192 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Monoclonal gammopathy 1/64 (1.6%) 0/192 (0%)
Nervous system disorders
Balance disorder 0/64 (0%) 1/192 (0.5%)
Diabetic neuropathy 0/64 (0%) 1/192 (0.5%)
Dizziness 1/64 (1.6%) 7/192 (3.6%)
Drooling 0/64 (0%) 1/192 (0.5%)
Dysarthria 0/64 (0%) 1/192 (0.5%)
Headache 6/64 (9.4%) 12/192 (6.3%)
Memory impairment 1/64 (1.6%) 0/192 (0%)
Paraesthesia 0/64 (0%) 1/192 (0.5%)
Restless legs syndrome 0/64 (0%) 1/192 (0.5%)
Somnolence 0/64 (0%) 2/192 (1%)
Tremor 1/64 (1.6%) 1/192 (0.5%)
Psychiatric disorders
Nervousness 1/64 (1.6%) 0/192 (0%)
Renal and urinary disorders
Nocturia 1/64 (1.6%) 0/192 (0%)
Pollakiuria 0/64 (0%) 2/192 (1%)
Polyuria 1/64 (1.6%) 0/192 (0%)
Proteinuria 0/64 (0%) 1/192 (0.5%)
Renal cyst 0/64 (0%) 1/192 (0.5%)
Renal impairment 1/64 (1.6%) 0/192 (0%)
Urinary incontinence 1/64 (1.6%) 0/192 (0%)
Urinary retention 0/64 (0%) 1/192 (0.5%)
Reproductive system and breast disorders
Prostatitis 1/64 (1.6%) 0/192 (0%)
Spontaneous penile erection 0/64 (0%) 2/192 (1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 0/64 (0%) 1/192 (0.5%)
Cough 1/64 (1.6%) 0/192 (0%)
Dyspnoea 0/64 (0%) 1/192 (0.5%)
Dyspnoea exertional 0/64 (0%) 1/192 (0.5%)
Epistaxis 0/64 (0%) 1/192 (0.5%)
Nasal congestion 0/64 (0%) 2/192 (1%)
Sinus congestion 0/64 (0%) 1/192 (0.5%)
Skin and subcutaneous tissue disorders
Alopecia 0/64 (0%) 1/192 (0.5%)
Dry skin 2/64 (3.1%) 0/192 (0%)
Hyperhidrosis 0/64 (0%) 1/192 (0.5%)
Neurodermatitis 0/64 (0%) 1/192 (0.5%)
Neuropathic ulcer 0/64 (0%) 1/192 (0.5%)
Night sweats 0/64 (0%) 1/192 (0.5%)
Pruritus 0/64 (0%) 3/192 (1.6%)
Pruritus generalised 0/64 (0%) 1/192 (0.5%)
Rash 1/64 (1.6%) 0/192 (0%)
Rash pruritic 0/64 (0%) 1/192 (0.5%)
Social circumstances
Immobile 0/64 (0%) 1/192 (0.5%)
Vascular disorders
Aortic aneurysm 0/64 (0%) 1/192 (0.5%)
Flushing 0/64 (0%) 1/192 (0.5%)
Hot flush 0/64 (0%) 1/192 (0.5%)
Hypertension 2/64 (3.1%) 9/192 (4.7%)
Hypotension 2/64 (3.1%) 0/192 (0%)
Orthostatic hypotension 0/64 (0%) 1/192 (0.5%)
Peripheral venous disease 1/64 (1.6%) 0/192 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer, Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01200394
Other Study ID Numbers:
  • A7331011
  • 2010-021358-20
First Posted:
Sep 13, 2010
Last Update Posted:
Mar 12, 2019
Last Verified:
Feb 1, 2019