A Phase 2 Multi-Center Study To Evaluate The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist In Adults With Type 2 Diabetes And Overt Nephropathy

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01712061
• Collaborator: (none)
• Enrollment: 226
• Locations: 142
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study hypothesis under test is that administration of a CCR2/5 antagonist to subjects with type 2 diabetes and overt nephropathy will result in a reduction in urinary albumin, a surrogate for improved glomerular filtration.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Nephropathy	Drug: PF-04634817; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 226 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 Chemokine Ccr2/5 Receptor Antagonist (Pf-04634817) In Adults With Type 2 Diabetes And Overt Nephropathy
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 PF-04634817	Drug: PF-04634817; Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function
Placebo Comparator: Arm 2 Placebo	Drug: Placebo; Three or four tablets (50mg) daily for 12 weeks, depending on baseline renal function

Outcome Measures

Primary Outcome Measures

1. Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12 [Baseline and Week 12]

   The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.

Secondary Outcome Measures

1. Change From Baseline in UACR at Weeks 4, 8 and 16 [Baseline, Weeks 4, 8 and 16]

   The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.

2. Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16 [Baseline, Weeks 4, 8, 12 and 16]

   The presence of protein in the urine (proteinuria) often implies kidney disease. Protein and creatinine concentrations were obtained from spot urine samples.

3. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16 [Baseline, Week 1, 4, 8, 12 and 16]

   eGFR was calculated using the MDRD equation and normalized to 1.73 m^2 body surface area. Age and corresponding creatinine at each visit (Weeks 1, 4, 8, 12 and 16) were used to calculate GFR

4. Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16 [Baseline, Week 12, and Week 16]

   Serum cystatin C may be a more reliable endogenous marker of GFR than serum creatinine. eGFR was calculated using the Cystatin Formula and normalized to 1.73 m^2 body surface area.

5. Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16 [Baseline, Week 1, 4, 8, 12 and 16]

   Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent. Change from baseline=creatinine level at Week 1, 4, 8, 12 or 16 minus baseline level where higher scores represented decreased kidney function.

6. Change From Baseline in Serum Cystatin C at Weeks 12 and 16 [Baseline, Week 12, and Week 16]

   Cystatin C is a protein which is mainly used as a biomarker of kidney function. If kidney function and GFR decline, the blood levels of cystatin C rise.

7. Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16 [Baseline, Weeks 4, 8, 12 and 16]

   HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. As the average amount of plasma glucose increases, the fraction of HbA1c increases in a predictable way.

8. Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12 [1, 2, 4 hours post-dose on Day 1; 2 hours post-dose on Weeks 1, 4, 8 and 12]

Other Outcome Measures

1. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16 [Baseline, Weeks 1, 4, 8, 12 and 16]

2. Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16 [Baseline, Weeks 1, 4, 8, 12 and 16]

3. Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16 [Baseline, Weeks 1, 4, 8, 12 and 16]

4. Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern [Baseline up to Week 16 (follow-up visit)]

   The following laboratory parameters were analyzed for abnormalities at any time point mentioned in the timeframe: clinical chemistry (sodium, potassium, chloride, bicarbonate, phosphate, glucose, blood urea nitrogen [BUN], creatinine, albumin, calcium, bilirubin [total, direct, and indirect], gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactic dehydrogenase [LDH], alkaline phosphatase, creatine phosphokinase [CPK], uric acid, amylase and lipase); hematology (hemoglobin, hematocrit, red blood cell [RBC] count, white blood cell [WBC] count with differential, and platelet count); FSH (for postmenopausal women who had been amenorrheic for less than 2 years prior to screening).

5. Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings [Baseline, Weeks 1, 4 and 12]

   Criteria for potentially clinically important ECG values were defined as: PR interval >=300 milliseconds (msec) or >=25%/50% increase when baseline is >200 msec and ≥50% increase when baseline is less than or equal to (<=)200 msec; QRS interval >=140 msec or >=50% increase from baseline (IFB); QTc >=450 msec or >=30 msec increase; corrected QT interval using Fridericia's formula (QTcF) >=450 msec or >=30 msec increase.

6. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Baseline up to 28 days after last study drug administration]

   An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. A SAE was 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 treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs.

7. Number of Participants With Increased Fasting Blood Glucose [Baseline up to Week 16 (follow-up visit)]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Clinical diagnosis of type 2 diabetes together with stages 2, 3a, 3b or 4 CKD, based on an eGFR of 20-75 mL/min/1.73m2.

• Evidence of persistent, overt albuminuria; defined as a UACR >=300 mg/g (>=33.9 mg/mmol) or UPCR >=390 mg/g (44.1 mg/mmol), or equivalent, for 3 months or longer.

• Stable background therapy of RAAS inhibition (ie, an ACE inhibitor and/or an ARB, which may also include an aldosterone antagonist in double RAAS but not triple RAAS inhibitor therapy) for at least 3 months before screening and to be maintained for the duration of the study.

Exclusion Criteria:

• Subjects with CKD resulting from type 1 diabetes or non-diabetic CKD.

• Subjects who are diagnosed with autosomal dominant polycystic kidney disease (ADPCKD), severe peripheral vascular disease (PVD) or obstructive uropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Investigations, Inc.	Little Rock	Arkansas	United States	72205
2	North America Research Institute	Azusa	California	United States	91702
3	California Institute of Renal Research	Chula Vista	California	United States	91910
4	California Kidney Specialists	Covina	California	United States	91723
5	Diabetes/Lipid Management and Research Center	Huntington Beach	California	United States	92648
6	Tower Nephrology Medical Group	Los Angeles	California	United States	90048
7	Richard S. Cherlin, MD	Los Gatos	California	United States	95032
8	Providence Clinical Research	North Hollywood	California	United States	91606
9	Desert Oasis Healthcare Medical Group	Palm Springs	California	United States	92262
10	Central Coast Nephrology	Salinas	California	United States	93901
11	California Kidney Specialists	San Dimas	California	United States	91773
12	University of Colorado Denver/University of Colorado Hospital	Aurora	Colorado	United States	80045
13	Gulf Coast Endocrine and Diabetes Center	Clearwater	Florida	United States	33756
14	Continental Research Corp.	Doral	Florida	United States	33126
15	Premier Research Associate, Inc.	Hialeah	Florida	United States	33012
16	Ocean Blue Medical Research Center, Inc	Miami Springs	Florida	United States	33166
17	Prestige Clinical Research Center	Miami	Florida	United States	33133
18	Elite Clinical Research	Miami	Florida	United States	33144
19	Nephrology Associates of South Miami	Miami	Florida	United States	33173
20	Tellus Clinical Research, Inc.	Miami	Florida	United States	33173
21	Diabetes Care Center	New Port Richey	Florida	United States	34652
22	Gulf Coast Kidney Center	New Port Richey	Florida	United States	34652
23	Suncoast Clinical Research, Inc.	New Port Richey	Florida	United States	34652
24	Pines Clinical Research, Inc.	Pembroke Pines	Florida	United States	33028
25	Christie Clinic, LLC	Champaign	Illinois	United States	61820
26	Four Rivers Clinical Research, Inc.	Paducah	Kentucky	United States	42003
27	Crescent City Clinical Research Center	Metairie	Louisiana	United States	70006
28	CTRC, Interim LSU Public Hospital	New Orleans	Louisiana	United States	70112
29	Pharmacy Department, Interim LSU Public Hospital	New Orleans	Louisiana	United States	70112
30	A. Kaldun Nossuli MD Research	Bethesda	Maryland	United States	20814
31	Western New England Renal and Transplant Associates, PC	Springfield	Massachusetts	United States	01107
32	Hurley Medical Center	Flint	Michigan	United States	48503
33	Apex Medical Research, MI, Inc.	Flint	Michigan	United States	48504
34	Troy Internal Medicine, PC	Troy	Michigan	United States	48098
35	Clinical Research Consultants, LLC	Kansas City	Missouri	United States	64111
36	VA Medical Center	Kansas City	Missouri	United States	64128
37	Creighton Diabetes Center	Omaha	Nebraska	United States	68131
38	Renal Medicine Associates	Albuquerque	New Mexico	United States	87109
39	Winthrop University Hospital, Division of Nephrology and Hypertension	Mineola	New York	United States	11501
40	Winthrop University Hospital, Pharmacy Department	Mineola	New York	United States	11501
41	Northport VA Medical Sciences Center	Northport	New York	United States	11768
42	Mountain Kidney and Hypertension Associates, PA	Asheville	North Carolina	United States	28801
43	East Carolina University Nephrology Research	Greenville	North Carolina	United States	27834
44	Down East Medical Associates, P.A.	Morehead City	North Carolina	United States	28557
45	Piedmont Healthcare/Research	Statesville	North Carolina	United States	28625
46	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina	United States	27103
47	Rhode Island Hospital	Providence	Rhode Island	United States	02903
48	BRAHN-Hypertension and Nephrology, Inc	Providence	Rhode Island	United States	02904
49	South Carolina Nephrology and Hypertension Center, Inc.	Orangeburg	South Carolina	United States	29118
50	The Endocrine Clinic, PC	Memphis	Tennessee	United States	38119
51	Nephrology Associates, P.C.	Nashville	Tennessee	United States	37205
52	Independent Clinical Research	Greenville	Texas	United States	75402
53	Clinical Trial Network	Houston	Texas	United States	77074
54	Southwest Nephrology Associates, LLP	Houston	Texas	United States	77074
55	Southwest Houston Research LTD	Houston	Texas	United States	77099
56	Southwest Nephrology Associates, LLP	Richmond	Texas	United States	77469
57	Clinical Advancement Center, PLLC	San Antonio	Texas	United States	78215
58	Briggs Clinical Research, LLC	San Antonio	Texas	United States	78224
59	San Antonio Kidney Disease Center Physicians Group, P.L.L.C.	San Antonio	Texas	United States	78229
60	Southwest Nephrology Associates, LLP	Sugar Land	Texas	United States	77478
61	Southern Utah Kidney and Hypertension	Saint George	Utah	United States	84770
62	Burke Internal Medicine & Research	Burke	Virginia	United States	22015
63	Clinical Research Institute of Northern Virginia, Inc.	Burke	Virginia	United States	22015
64	Manassas Clinical Research Center	Manassas	Virginia	United States	20110
65	Zablocki Veterans Affairs Medical Center	Milwaukee	Wisconsin	United States	53295
66	Centro de Salud Renal Junin S.R.L.	Junin	Buenos Aires	Argentina	6000
67	Centro de Investigaciones Medicas - Clinica de Fracturas y Ortopedia	Mar del Plata	Buenos Aires	Argentina	B7600DHK
68	Instituto de Investigaciones Clinicas Quilmes S.R.L	Quilmes	Buenos Aires	Argentina	B1878GEG
69	Instituto de Cardiologia de Corrientes "Juana Francisca Cabral"	Corrientes		Argentina	W3400AMZ
70	Centro de Investigaciones Clinicas del Litoral S.R.L.	Santa Fe		Argentina	3000
71	CETENE S.A. - Centro de Nefrologia y Dialisis	Tucumán		Argentina	T4000IIO
72	Liverpool Hospital	Liverpool	New South Wales	Australia	2170
73	Department of Nephrology	New Lambton	New South Wales	Australia	2305
74	Westmead Hospital, Department of Renal Medicine	Westmead	New South Wales	Australia	2145
75	Sunshine Coast Hospital & Health Service	Nambour	Queensland	Australia	4560
76	Box Hill Hospital	Box Hill	Victoria	Australia	3128
77	Monash Medical Centre	Clayton	Victoria	Australia	3168
78	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
79	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1L8
80	BC Diabetes.ca	Vancouver	British Columbia	Canada	V5Z 1M9
81	Co-Medica Research Network Inc.	Courtice	Ontario	Canada	L1E 3C3
82	OTT Healthcare Incorporated	Scarborough	Ontario	Canada	M1H 3G4
83	Dr. Stephen S. Chow Medicine Professional Corporation	Toronto	Ontario	Canada	M4C 5T2
84	Toronto East General Medical Centre	Toronto	Ontario	Canada	M4C 5T2
85	Centre de Recherche Clinique de Laval	Laval	Quebec	Canada	H7T 2P5
86	Hopital Maisonneuve-Rosemont-Nephrology	Montreal	Quebec	Canada	H1T 2M4
87	Hopital Du Sacre-Coeur de Montreal Centre de recherche	Montreal	Quebec	Canada	H4J 1C5
88	Pro-Recherche	St-Romuald	Quebec	Canada	G6W 5M6
89	Dialysezentrum Elsterland	Herzberg	Brandenburg	Germany	04916
90	Studienzentrum Haematologie/Onkologie/Diabetologie	Aschaffenburg		Germany	63739
91	Universitatsmedizin Berlin - Charite Campus Mitte	Berlin		Germany	10117
92	GWT-TUD GmbH	Dresden		Germany	01307
93	Studienzentrum Karlstrasse GmbH	Duesseldorf		Germany	40210
94	Profil Institut fuer Stoffwechselforschung GmbH (branch: Diabetes Praxis Essen)	Essen		Germany	45136
95	Diabetes Schwerpunktpraxis / Zentrum fur Klinische Studien	Falkensee		Germany	14612
96	Medizinische Hochschule Hannover	Hannover		Germany	30625
97	Nephrologisches Zentrum Hoyerswerda	Hoyerswerda		Germany	02977
98	Zentrum Klinische Studien Neuwied	Neuwied		Germany	D-56564
99	Diabetologische Schwerpunktpraxis	Schwabenheim		Germany	55270
100	Department of Medicine and Therapeutics, Prince of Wales Hospital,	Shatin, New Territories	Hong Kong SAR	Hong Kong
101	Department of Medicine and Therapeutics	Shatin, New Territories	Hong Kong SAR	Hong Kong
102	Queen Mary Hospital	Hong Kong		Hong Kong
103	AOU Consorziale Policlinico di Bari	Bari	BA	Italy	70124
104	Ospedale Versilia	Lido Camaiore. (Lucca)	Lucca	Italy	55041
105	*Ospedale Versilia	Lido di Camaiore (LUCCA)	Lucca	Italy	55043
106	Ospedale Versilia	Lido di Camaiore (LUCCA)	Lucca	Italy	55043
107	A.O.U. Policlinico di Modena	Modena	MO	Italy	41124
108	Azienda Ospedaliera Ospedali Riuniti di Foggia	Foggia		Italy	71100
109	Ospedale Alessandro Manzoni	Lecco		Italy	23900
110	Unita Cardiometabolica e Trials Clinici	Milano		Italy	20132
111	Fondazione Salvatore Maugeri Clinica del Lavoro e della Riabilitazione IRCCS	Pavia		Italy	27100
112	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
113	Yonsei University College of Medicine, Severance Hospital	Seoul		Korea, Republic of	120-752
114	Chung-Ang University Hospital	Seoul		Korea, Republic of	156-755
115	Hospital Universiti Sains Malaysia	Kubong Kerian	Kelantan	Malaysia	16150
116	Hospital Taiping	Taiping	Perak	Malaysia	34000
117	Selayang Hospital	Batu Caves	Selangor	Malaysia	68100
118	Casa de Diabetes y Nutricion	Lima		Peru	17
119	Centro de Investigacion y Atencion Cardiovascular S.A.C. - Clinica Novocardio	Lima		Peru	27
120	Consultorio de Endocrinologia - LM Servicios Medicos y Endocrinologicos EIRL	Lima		Peru	27
121	Clinica Maison de Sante ¿ Sede este	Lima		Peru	LIMA 33
122	Clinica Virgen Maria Auxiliadora	Piura		Peru	073
123	Krakowskie Centrum Medyczne Sp. z.o.o.	Krakow	Malopolskie	Poland	31-501
124	Stacja Dializ	Golub-Dobrzyn		Poland	87-400
125	LANDA Specjalistyczne Gabinety Lekarskie	Krakow		Poland	30-015
126	SCM Sp. z.o.o	Krakow		Poland	31-559
127	Klinika Nefrologii, Hipertensjologii i Transplantologii Nerek	Lodz		Poland	92-013
128	NZOZ TRI-medica	Lodz		Poland	93-338
129	CSK MSW w Warszawie Klinika Chorob Wewnetrznych Endokrynologii i Diabetologii	Warszawa		Poland	02-507
130	KO-MED, Central Kliniczne Sp. z.o.o	Zamosc		Poland	22-400
131	Ponce School of Medicine - CAIMED Center	Ponce		Puerto Rico	00716
132	Medical Sciences Campus University of Puerto Rico	Rio Piedras		Puerto Rico	00935
133	Spital Clinic Municipal "Dr. Gavril Curteanu" Oradea	Oradea	jud. Bihor	Romania	410469
134	Institutul National de Diabet, Nutritie si Boli Metabolice	Bucuresti		Romania	020475
135	Elit Medical SRL, Diabet Zaharat Nutritie si Boli Metabolice	Ploiesti		Romania	100018
136	Spitalul Clinic Judetean de Urgenta Timisoara	Timisoara		Romania	300736
137	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona	Spain	08907
138	Hospital Puerta de Hierro	Majadahonda	Madrid	Spain	28222
139	Parc de Salut Mar. Hospital del Mar	Barcelona		Spain	08003
140	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
141	Hospital Universitari de Girona Dr. Josep Trueta	Girona		Spain	17007
142	Hospital Universitario Dr Peset	Valencia		Spain	46017

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01712061
• Other Study ID Numbers: B1261007; 2012-003332-23
• First Posted: Oct 23, 2012
• Last Update Posted: Oct 21, 2015
• Last Verified: Sep 1, 2015

• Keywords provided by Pfizer: Diabetic nephropathy; type 2 diabetes; albuminuria; chemokine antagonist
• Additional relevant MeSH terms: Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Pre-assignment Detail	The primary entry criterion for participants was based on presence of macroalbuminuria (urine albumin to creatinine ratio [UACR] greater than or equal to (>=)300 milligrams per gram (mg/g).

Arm/Group Title	PF-04634817 150 mg	PF-04634817 200 mg	Placebo
Arm/Group Description	Participants with estimated glomerular filtration rate (eGFR) values of 20 to less than (<)30 milliliters/minute (mL/min)/1.73 square meter (m^2) were dosed orally at 150 mg once daily (QD) for 12 weeks.	Participants with eGFR values of 30 to 75 mL/min/1.73 m^2 were dosed orally at 200 mg QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Period Title: Overall Study
STARTED	30	140	56
COMPLETED	20	114	45
NOT COMPLETED	10	26	11

Baseline Characteristics

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo	Total
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.	Total of all reporting groups
Overall Participants	170	56	226
Age, Customized (participants) [Number]
Less than (<) 18 years	0 0%	0 0%	0 0%
18-44 years	3 1.8%	0 0%	3 1.3%
45-64 years	78 45.9%	31 55.4%	109 48.2%
>=65 years	89 52.4%	25 44.6%	114 50.4%
Sex: Female, Male (Count of Participants)
Female	36 21.2%	7 12.5%	43 19%
Male	134 78.8%	49 87.5%	183 81%

Outcome Measures

1. Primary Outcome

Title	Percent Reduction From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12
Description	The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	159	51
Mean (95% Confidence Interval) [percent (%)]	13.27 (5.43)	5.02 (6.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg/150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric mean changes
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in UACR at Weeks 4, 8 and 16
Description	The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.
Time Frame	Baseline, Weeks 4, 8 and 16

Outcome Measure Data

Analysis Population Description

The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	159	51
Baseline (n=157,50)	127.41 (96)	121.80 (88)
Change From Baseline at Week 4 (n=148,46)	0.89 (66)	0.91 (88)
Change From Baseline at Week 8 (n=134,43)	0.90 (62)	0.94 (57)
Change From Baseline at Week 16 (n=126,37)	0.93 (72)	0.92 (56)

3. Secondary Outcome

Title	Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 4, 8, 12 and 16
Description	The presence of protein in the urine (proteinuria) often implies kidney disease. Protein and creatinine concentrations were obtained from spot urine samples.
Time Frame	Baseline, Weeks 4, 8, 12 and 16

Outcome Measure Data

Analysis Population Description

The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	159	51
Baseline (n=155,49)	185.42 (97)	176.31 (82)
Change From Baseline at Week 4 (n=143,45)	0.93 (47)	0.92 (76)
Change From Baseline at Week 8 (n=130,42)	0.92 (50)	0.94 (46)
Change From Baseline at Week 12 (n=125,42)	0.92 (58)	0.92 (79)
Change From Baseline at Week 16 (n=125,36)	0.95 (58)	0.92 (55)

4. Secondary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Abbreviated Modified Diet in Renal Disease (MDRD) Formula at Weeks 1, 4, 8, 12 and 16
Description	eGFR was calculated using the MDRD equation and normalized to 1.73 m^2 body surface area. Age and corresponding creatinine at each visit (Weeks 1, 4, 8, 12 and 16) were used to calculate GFR
Time Frame	Baseline, Week 1, 4, 8, 12 and 16

Outcome Measure Data

Analysis Population Description

The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	159	51
Baseline (n=159,51)	41.80 (12.18)	41.65 (13.46)
Change From Baseline at Week 1 (n=157,50)	-0.77 (5.80)	-0.35 (5.28)
Change From Baseline at Week 4 (n=157,51)	-1.07 (5.37)	-1.32 (5.12)
Change From Baseline at Week 8 (n=147,47)	-1.60 (5.34)	-2.15 (6.83)
Change From Baseline at Week 12 (n=136,45)	-1.14 (5.70)	-1.03 (5.75)
Change From Baseline at Week 16 (n=134,44)	-2.14 (6.42)	-1.18 (5.58)

5. Secondary Outcome

Title	Change From Baseline in eGFR Using Cystatin Formula at Weeks 12 and 16
Description	Serum cystatin C may be a more reliable endogenous marker of GFR than serum creatinine. eGFR was calculated using the Cystatin Formula and normalized to 1.73 m^2 body surface area.
Time Frame	Baseline, Week 12, and Week 16

Outcome Measure Data

Analysis Population Description

The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	159	51
Baseline (n=159,50)	45.28 (14.22)	45.36 (14.94)
Change From Baseline at Week 12 (n=135,44)	-1.10 (6.30)	-0.70 (5.49)
Change From Baseline at Week 16 (n=134,43)	-2.27 (6.77)	-0.91 (6.30)

6. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at Weeks 1, 4, 8, 12 and 16
Description	Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent. Change from baseline=creatinine level at Week 1, 4, 8, 12 or 16 minus baseline level where higher scores represented decreased kidney function.
Time Frame	Baseline, Week 1, 4, 8, 12 and 16

Outcome Measure Data

Analysis Population Description

The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	159	51
Baseline (n=159,51)	1.72 (0.51)	1.77 (0.51)
Change From Baseline at Week 1 (n=158,50)	0.05 (0.22)	0.03 (0.17)
Change From Baseline at Week 4 (n=157,51)	0.06 (0.21)	0.11 (0.30)
Change From Baseline at Week 8 (n=147,47)	0.06 (0.21)	0.09 (0.24)
Change From Baseline at Week 12 (n=137,45)	0.05 (0.24)	0.08 (0.20)
Change From Baseline at Week 16 (n=134,44)	0.09 (0.30)	0.09 (0.29)

7. Secondary Outcome

Title	Change From Baseline in Serum Cystatin C at Weeks 12 and 16
Description	Cystatin C is a protein which is mainly used as a biomarker of kidney function. If kidney function and GFR decline, the blood levels of cystatin C rise.
Time Frame	Baseline, Week 12, and Week 16

Outcome Measure Data

Analysis Population Description

The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	159	51
Baseline (n=159,51)	1.54 (0.43)	1.52 (0.41)
Change From Baseline at Week 12 (n=136,45)	0.03 (0.25)	0.03 (0.21)
Change From Baseline at Week 16 (n=134,44)	0.05 (0.26)	0.06 (0.25)

8. Secondary Outcome

Title	Change From Baseline in Plasma Glycosylated Hemoglobin (HbA1c) at Weeks 4, 8, 12 and 16
Description	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. As the average amount of plasma glucose increases, the fraction of HbA1c increases in a predictable way.
Time Frame	Baseline, Weeks 4, 8, 12 and 16

Outcome Measure Data

Analysis Population Description

The FAS was defined as all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 post-dose efficacy measurement; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	159	51
Baseline (n=159,51)	7.51 (1.22)	7.91 (1.42)
Change From Baseline at Week 4 (n=157,51)	0.03 (0.46)	-0.04 (0.46)
Change From Baseline at Week 8 (n=147,46)	-0.02 (0.64)	-0.08 (0.71)
Change From Baseline at Week 12 (n=137,44)	-0.01 (0.76)	-0.06 (0.81)
Change From Baseline at Week 16 (n=133,44)	0.04 (0.89)	-0.04 (1.13)

9. Secondary Outcome

Title	Summary of Plasma PF-04634817 Pharmacokinetic (PK) Concentrations at Day 1 and Weeks 1, 4, 8 and 12
Time Frame	1, 2, 4 hours post-dose on Day 1; 2 hours post-dose on Weeks 1, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The PK Concentration Analysis Set is defined as all participants in the FAS for whom a PK sample was obtained and analyzed; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 150 mg	PF-04634817 200 mg
Arm/Group Description	Participants with estimated glomerular filtration rate (eGFR) values of 20 to less than (<)30 milliliters/minute (mL/min)/1.73 square meter (m^2) were dosed orally at 150 mg once daily (QD) for 12 weeks.	Participants with eGFR values of 30 to 75 mL/min/1.73 m^2 were dosed orally at 200 mg QD for 12 weeks.
Measure Participants	30	140
Day 1: 1 Hour Post-Dose (n=29,124)	434.5 (65)	524.4 (83)
Day 1: 2 Hours Post-Dose (n=30,139)	579.3 (37)	602.9 (52)
Day 1: 4 Hours Post-Dose (n=29,137)	497.4 (38)	547.7 (46)
Week 1: Pre-Dose (n=28,131)	294.4 (60)	231.2 (73)
Week 1: 2 Hours Post-Dose (n=28,132)	884.8 (42)	865.0 (55)
Week 4: Pre-Dose (n=25,126)	231.3 (51)	239.5 (87)
Week 4: 2 Hours Post-Dose (n=24,122)	785.8 (45)	918 (55)
Week 8: Pre-Dose (n=23,113)	310.2 (79)	245.2 (77)
Week 8: 2 Hours Post-Dose (n=23,114)	730.0 (70)	895 (57)
Week 12 (n=20,113)	320.1 (75)	252.3 (84)

10. Other Pre-specified Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 1, 4, 8, 12 and 16
Time Frame	Baseline, Weeks 1, 4, 8, 12 and 16

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	170	56
Supine SBP: Baseline (n=168,53)	140.4 (13.96)	139.9 (13.60)
Supine SBP:Change From Baseline Week 1 (n=164,53)	-0.8 (12.75)	-1.6 (12.87)
Supine SBP:Change From Baseline Week 4 (n=154,49)	-0.5 (15.43)	-1.6 (14.19)
Supine SBP:Change From Baseline Week 8 (n=142,47)	-3.4 (12.94)	-1.1 (13.71)
Supine SBP:Change From Baseline Week 12 (n=134,45)	-2.0 (13.28)	-1.3 (13.23)
Supine SBP:Change From Baseline Week 16 (n=138,45)	-2.4 (15.14)	-0.3 (14.41)
Supine DBP: Baseline (n=168,53)	75.9 (8.97)	77.1 (6.88)
Supine DBP:Change From Baseline Week 1 (n=164,53)	-0.2 (6.94)	-2.7 (7.58)
Supine DBP:Change From Baseline Week 4 (n=154,49)	0.1 (8.23)	-1.8 (7.47)
Supine DBP:Change From Baseline Week 8 (n=142,47)	-1.9 (7.46)	-1.5 (7.05)
Supine DBP:Change From Baseline Week 12 (n=134,45)	-0.9 (6.88)	-0.2 (6.69)
Supine DBP:Change From Baseline Week 16 (n=138,45)	-1.7 (7.98)	0.9 (8.40)

11. Other Pre-specified Outcome

Title	Change From Baseline in Pulse Rate at Weeks 1, 4, 8, 12 and 16
Time Frame	Baseline, Weeks 1, 4, 8, 12 and 16

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	170	56
Baseline (n=168,53)	68.7 (9.74)	69.3 (9.30)
Change From Baseline at Week 1 (n=164,53)	0.1 (5.86)	-0.7 (5.63)
Change From Baseline at Week 4 (n=154,49)	0.3 (6.01)	-1.0 (6.63)
Change From Baseline at Week 8 (n=142,47)	0.2 (6.54)	1.4 (6.77)
Change From Baseline at Week 12 (n=134,45)	0.2 (7.03)	0.5 (7.33)
Change From Baseline at Week 16 (n=138,45)	1.4 (8.22)	-0.1 (6.92)

12. Other Pre-specified Outcome

Title	Change From Baseline in Body Weight at Weeks 1, 4, 8, 12 and 16
Time Frame	Baseline, Weeks 1, 4, 8, 12 and 16

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	170	56
Baseline (n=167,53)	93.8 (23.97)	95.1 (25.95)
Change From Baseline at Week 1 (n=163,53)	0.0 (1.03)	0.3 (1.42)
Change From Baseline at Week 4 (n=153,49)	-0.0 (1.74)	0.4 (3.29)
Change From Baseline at Week 8 (n=141,47)	0.1 (2.45)	0.7 (2.74)
Change From Baseline at Week 12 (n=134,45)	0.3 (2.66)	0.7 (3.02)
Change From Baseline at Week 16 (n=137,45)	-0.1 (2.79)	0.2 (3.37)

13. Other Pre-specified Outcome

Title	Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern
Description	The following laboratory parameters were analyzed for abnormalities at any time point mentioned in the timeframe: clinical chemistry (sodium, potassium, chloride, bicarbonate, phosphate, glucose, blood urea nitrogen [BUN], creatinine, albumin, calcium, bilirubin [total, direct, and indirect], gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactic dehydrogenase [LDH], alkaline phosphatase, creatine phosphokinase [CPK], uric acid, amylase and lipase); hematology (hemoglobin, hematocrit, red blood cell [RBC] count, white blood cell [WBC] count with differential, and platelet count); FSH (for postmenopausal women who had been amenorrheic for less than 2 years prior to screening).
Time Frame	Baseline up to Week 16 (follow-up visit)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; number of participants analyzed (N) is number of evaluable participants for this outcome measure.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	167	53
Number [participants]	154 90.6%	49 87.5%

14. Other Pre-specified Outcome

Title	Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Description	Criteria for potentially clinically important ECG values were defined as: PR interval >=300 milliseconds (msec) or >=25%/50% increase when baseline is >200 msec and ≥50% increase when baseline is less than or equal to (<=)200 msec; QRS interval >=140 msec or >=50% increase from baseline (IFB); QTc >=450 msec or >=30 msec increase; corrected QT interval using Fridericia's formula (QTcF) >=450 msec or >=30 msec increase.
Time Frame	Baseline, Weeks 1, 4 and 12

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; n=number of participants analyzed in respective arms for category.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	170	56
Maximum PR Interval >=300 msec (n=164,55)	3 1.8%	0 0%
Maximum QRS Complex >=140 msec (n=169,56)	2 1.2%	1 1.8%
Maximum QT Interval >=500 msec (n=169,56)	0 0%	0 0%
Maximum QTc Interval 450-<480 msec (n=169,56)	23 13.5%	11 19.6%
Maximum QTc Interval 480-<500 msec (n=169,56)	4 2.4%	1 1.8%
Maximum QTc Interval >=500 msec (n=169,56)	0 0%	0 0%
Maximum QTcF Interval 450-<480 msec (n=169,56)	11 6.5%	5 8.9%
Maximum QTcF Interval 480-<500 msec (n=169,56)	1 0.6%	1 1.8%
Maximum QTcF Interval >=500 msec (n=169,56)	1 0.6%	0 0%
PR Interval >=25/50% IFB (n=163,53)	3 1.8%	0 0%
QRS Complex >=50% IFB (n=169,55)	3 1.8%	0 0%
QTc Interval 30-<60 msec IFB (n=169,55)	15 8.8%	4 7.1%
QTc Interval >=60 msec IFB (n=169,55)	0 0%	0 0%
QTcF Interval 30-<60 msec IFB (n=169,55)	8 4.7%	3 5.4%
QTcF Interval >=60 msec IFB (n=169,55)	1 0.6%	0 0%

15. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. A SAE was 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 treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs.
Time Frame	Baseline up to 28 days after last study drug administration

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	170	56
AEs	106 62.4%	36 64.3%
SAEs	17 10%	5 8.9%

16. Other Pre-specified Outcome

Title	Number of Participants With Increased Fasting Blood Glucose
Time Frame	Baseline up to Week 16 (follow-up visit)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set is defined as all participants who receive at least 1 dose of study medication; number of participants analyzed (N) is number of evaluable participants for this outcome measure.

Arm/Group Title	PF-04634817 200 mg/150 mg	Placebo
Arm/Group Description	Participants were dosed orally at 150 mg (eGFR 20-<30 mL/min/1.73 m^2) or 200 mg (30-75 mL/min/1.73 m^2) QD for 12 weeks.	Participants were dosed orally with matching placebo tablets QD for 12 weeks.
Measure Participants	167	53
Number [participants]	1 0.6%	0 0%

Adverse Events

Time Frame	Baseline up to 28 days after last study drug administration
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 non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Arm/Group Title	PF-04634817 150 mg		PF-04634817 200 mg		Placebo
Arm/Group Description	Participants with estimated glomerular filtration rate (eGFR) values of 20 to less than (<)30 milliliters/minute (mL/min)/1.73 square meter (m^2) were dosed orally at 150 mg once daily (QD) for 12 weeks.		Participants with eGFR values of 30 to 75 mL/min/1.73 m^2 were dosed orally at 200 mg QD for 12 weeks.		Participants were dosed orally with matching placebo tablets QD for 12 weeks.
All Cause Mortality
	PF-04634817 150 mg		PF-04634817 200 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PF-04634817 150 mg		PF-04634817 200 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/30 (20%)		11/140 (7.9%)		5/56 (8.9%)
Cardiac disorders
Cardiac failure	1/30 (3.3%)		0/140 (0%)		0/56 (0%)
Gastrointestinal disorders
Gastritis	0/30 (0%)		1/140 (0.7%)		0/56 (0%)
Pancreatitis acute	0/30 (0%)		1/140 (0.7%)		0/56 (0%)
General disorders
Chest pain	0/30 (0%)		2/140 (1.4%)		0/56 (0%)
Generalised oedema	0/30 (0%)		1/140 (0.7%)		0/56 (0%)
Pyrexia	0/30 (0%)		1/140 (0.7%)		0/56 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/30 (0%)		1/140 (0.7%)		0/56 (0%)
Infections and infestations
Cellulitis	0/30 (0%)		0/140 (0%)		1/56 (1.8%)
Localised infection	0/30 (0%)		0/140 (0%)		1/56 (1.8%)
Pneumonia	2/30 (6.7%)		1/140 (0.7%)		1/56 (1.8%)
Septic shock	1/30 (3.3%)		0/140 (0%)		0/56 (0%)
Viral infection	0/30 (0%)		1/140 (0.7%)		0/56 (0%)
Metabolism and nutrition disorders
Dehydration	1/30 (3.3%)		0/140 (0%)		0/56 (0%)
Hypokalaemia	1/30 (3.3%)		0/140 (0%)		0/56 (0%)
Musculoskeletal and connective tissue disorders
Gouty arthritis	1/30 (3.3%)		0/140 (0%)		0/56 (0%)
Nervous system disorders
Cerebral infarction	0/30 (0%)		1/140 (0.7%)		0/56 (0%)
Dizziness	1/30 (3.3%)		0/140 (0%)		0/56 (0%)
Renal and urinary disorders
Renal failure acute	2/30 (6.7%)		2/140 (1.4%)		0/56 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/30 (0%)		0/140 (0%)		1/56 (1.8%)
Skin and subcutaneous tissue disorders
Dermatitis	1/30 (3.3%)		0/140 (0%)		0/56 (0%)
Erythrodermic psoriasis	1/30 (3.3%)		0/140 (0%)		0/56 (0%)
Social circumstances
Homicide	0/30 (0%)		0/140 (0%)		1/56 (1.8%)
Vascular disorders
Hypertension	0/30 (0%)		1/140 (0.7%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	PF-04634817 150 mg		PF-04634817 200 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/30 (36.7%)		40/140 (28.6%)		15/56 (26.8%)
Gastrointestinal disorders
Diarrhoea	2/30 (6.7%)		12/140 (8.6%)		3/56 (5.4%)
Nausea	2/30 (6.7%)		5/140 (3.6%)		2/56 (3.6%)
General disorders
Oedema peripheral	3/30 (10%)		8/140 (5.7%)		4/56 (7.1%)
Infections and infestations
Nasopharyngitis	2/30 (6.7%)		6/140 (4.3%)		3/56 (5.4%)
Upper respiratory tract infection	2/30 (6.7%)		5/140 (3.6%)		2/56 (3.6%)
Investigations
Gamma-glutamyltransferase increased	2/30 (6.7%)		1/140 (0.7%)		0/56 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	2/30 (6.7%)		1/140 (0.7%)		1/56 (1.8%)
Hypoglycaemia	2/30 (6.7%)		2/140 (1.4%)		1/56 (1.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/30 (6.7%)		2/140 (1.4%)		1/56 (1.8%)
Nervous system disorders
Dizziness	2/30 (6.7%)		4/140 (2.9%)		1/56 (1.8%)
Renal and urinary disorders
Dysuria	2/30 (6.7%)		0/140 (0%)		1/56 (1.8%)
Vascular disorders
Hypertension	1/30 (3.3%)		6/140 (4.3%)		3/56 (5.4%)

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.