A Phase 2, Multi-Center Study To Compare The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist With Ranibizumab In Adults With Diabetic Macular Edema

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01994291
• Collaborator: (none)
• Enrollment: 199
• Locations: 63
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study hypothesis under test is that administration of the CCR2/5 antagonist has the potential to be as effective as the current treatment options for subjects with diabetic macular edema. The current treatment option for these subjects is an injection directly into the eye, while this CCR2/5 antagonist would be an oral drug which has the potential to be just as effective. This CCR2/5 antagonist also has a broader anti-inflammatory potential and might be able to provide an alternative mechanism to treat Diabetic Macular Edema.

Condition or Disease	Intervention/Treatment	Phase
Macular Edema, Diabetic	Drug: Ranibizumab; Drug: Placebo; Drug: PF-04634817; Drug: Masked Sham Therapy	Phase 2

Detailed Description

Study recruitment was stopped on April 9, 2015. This decision was taken for business reasons due to changes in the prioritization of the drug development portfolio. This decision was not as a result of any evolving safety, efficacy issue or changes in the risk:benefit assessment of this product or regulatory interactions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 199 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel Group, Multi-Center Study To Compare The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist (PF-04634817) With That Of Ranibizumab In Adult Subjects With Diabetic Macular Edema
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 Intravitreal administration of ranibizumab (either 0.3 or 0.5 mg, given monthly, as detailed in the prescribing information and label content approved for the country governing the study site) plus an oral placebo.	Drug: Ranibizumab; Intravitreal Injection supplied as: 10 mg/mL in a 0.2 mL vial with instructions on preparation and administration of the 0.5 mg (0.05 mL) dose. 6 mg/mL in a single use vial with instructions on preparation and administration of the 0.3 mg (0.05 mL) dose. Adminstered once a month for 12 weeks; Drug: Placebo; Oral Placebo is provided in tablet form to match the 50mg dose of PF-04634817. Dose is 4 tablets each day for 12 weeks
Experimental: Arm 2 Oral PF-04634817 200 mg, once daily plus a masked sham therapy (given monthly).	Drug: PF-04634817; Four 50mg tablets PF-04634817 once a day for 12 weeks.; Drug: Masked Sham Therapy; Empty, needle-less syringe is used by the unmasked team once a month.

Outcome Measures

Primary Outcome Measures

1. Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA) [Baseline (Day 0) and Week 12]

   Refraction and visual acuity were assessed through the BCVA obtained using the retro illuminated early treatment diabetic retinopathy study (ETDRS) charts. Distance visual acuity was expressed as an ETDRS score (number of letters correctly read).

Secondary Outcome Measures

1. Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12 [Baseline (Day 0) and Week 12]

   Refraction and visual acuity were assessed through the BCVA obtained using the retro illuminated ETDRS charts. Distance visual acuity was expressed as an ETDRS score (number of letters correctly read).

2. Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12 [Baseline (Day 0) and Week 12]

   A central reading center was used for the evaluation. A photographer or technician pre certified ("study certified") by the Central Reading Center ought to perform all optical coherence tomography (OCT) imaging. Use of a Spectralis or Cirrus OCT was acceptable.

3. Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12 [Baseline (Day 0) and Week 12]

   Fluorescein Angiography (FA) using certified digital systems was taken by a photographer who had been pre-certified ("study-certified") by the Central Reading Center. They were evaluated by the Central Reading Center.

4. Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12 [Baseline (Day 0) and Week 12]

   Stereo color fundus photographs using certified digital systems were taken by a photographer who had been pre-certified ("study certified") by the Central Reading Center. They were evaluated by the Central Reading Center.

5. Plasma Concentration of PF-04634817 up to Week 12 [Week 0, Week 4, Week 8, and Week 12]

Other Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Week 0 to Week 16]

   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.

2. Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs [Week -5 to Week 16]

   Number of participants who met the categorical summary of post-baseline criteria at any time point, defined as: supine pulse rate <40 beats per minute (bpm) or >120 bpm; supine systolic blood pressure (SBP) ≥30 millimeters of mercury (mmHg) change from baseline in same posture; supine diastolic BP (DBP) ≥20 mmHg change from baseline in same posture; supine SBP <90 mmHg; supine DBP <50 mmHg.

3. Number of Participants With Laboratory Abnormalities [Week -5 to Week 16]

   The following laboratory parameters were analyzed for abnormalities at any time point: hematology (hemoglobin, hematocrit, red blood cell count (RBC), white blood cell count (WBC) with differential, and platelet count); blood chemistry (sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, albumin, calcium, total, direct and indirect bilirubin, gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), alkaline phosphatase, creatine phosphokinase (CPK), uric acid, amylase and lipase); follicle-stimulating hormone (FSH) (Weeks -5 to 0 only, for postmenopausal women who have been amenorrheic for at least 12 consecutive months prior to screening visit).

4. Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings [Week -5 to Week 16]

   ECG parameters included PR interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval greater than or equal to (>=)300 milliseconds (msec) or >=25% increase when baseline is greater than (>)200 msec and >=50% increase when baseline is less than or equal to (≤)200 msec; QRS interval >=200 msec or >=25% increase when baseline is greater than (>)200 msec and >=50% increase when baseline is less than or equal to (≤)200 msec; QT interval >=500 msec; and QTcF >=450 msec or >=30 msec increase. The number of participants with potentially clinically significant ECG findings at any visit were reported.

5. Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 [Week -5 to Week 16]

   The anterior biomicroscopy exam was done undilated in order to assess whether there was any anterior segment inflammation caused either by ranibizumab or PF-04634817.

6. Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye [Week -5 to Week 16]

   IOP was measured using Goldmann applanation tonometry. To maintain consistency, it was recommended that the same examiner ought to measure IOP with the same tonometer at each visit for a given subject. Intraocular pressure ought to be measured in the study eye approximately 30 minutes after intravitreal injection or masked sham therapy (performed by unmasked study team member).

7. Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 [Week -5 to Week 16]

   Ophthalmoscopy ought to be performed after pupillary dilation to examine the vitreous body, optic nerve head, macular and peripheral retina. All findings, including the presence or absence of vitreous inflammation, ought to be documented. All post-dose ophthalmoscopy assessments ought to be made immediately following the administration of ranibizumab or masked sham therapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with Diabetes Mellitus (Type 1 or Type 2) Showing Diabetic Macular Edema in the Eye

• Reduced visual acuity resulting from retinal thickening

• Female subjects of non-childbearing potential ≥18 years and male subjects greater than or equal to 18 years. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

• Female subjects who are not of childbearing potential must meet at least one of the following criteria:

• Have undergone a documented hysterectomy and/or bilateral oophorectomy;

• Have medically confirmed ovarian failure; or

• Achieved post-menopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females.

Exclusion Criteria:

• Severe Impaired Renal Function

• Any intraocular condition or previous surgery in either eye that would likely require medical or surgical intervention during the study duration or if allowed to progress untreated for the 16 weeks of study duration, would likely contribute to a reduction in visual acuity.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina Research Institute, LLC	Phoenix	Arizona	United States	85014
2	Retinal Consultants of Arizona	Phoenix	Arizona	United States	85014
3	Sunny View Medical Center	Phoenix	Arizona	United States	85018
4	Premier Research Group Limited	Phoenix	Arizona	United States	85027
5	Retina Centers, P.C.	Tucson	Arizona	United States	85704
6	Retina Institute of California	Arcadia	California	United States	91007
7	Retina Vitreous Associates Medical Group	Beverly Hills	California	United States	90211
8	Retinal Diagnostic Center	Campbell	California	United States	95008
9	Retina Associates of Orange County	Laguna Hills	California	United States	92653
10	Southern California Desert Retina Consultants	Palm Desert	California	United States	92211
11	American Institute of Research (Administrative Only)	Whittier	California	United States	90603
12	New England Retina Associates	New London	Connecticut	United States	06320
13	Bascom Palmer Eye Institute	Miami	Florida	United States	33136
14	Fort Lauderdale Eye Institute	Plantation	Florida	United States	33324
15	Center for Retina and Macular Disease	Winter Haven	Florida	United States	33880
16	Southeast Retina Center, PC	Augusta	Georgia	United States	30909
17	Midwest Eye Institute	Indianapolis	Indiana	United States	46290
18	Tufts Medical Center	Boston	Massachusetts	United States	02111
19	TLC Eyecare & Laser Center	Jackson	Michigan	United States	49202
20	Wm Beaumont Medical Office Building	Royal Oak	Michigan	United States	48073
21	Charlotte Eye Ear Nose and Throat Associates PA	Charlotte	North Carolina	United States	28210
22	Retina Associates of Cleveland, Inc.	Cleveland	Ohio	United States	44122
23	Retina Associates of Cleveland	Youngstown	Ohio	United States	44505
24	Dean McGee Eye Institute	Oklahoma City	Oklahoma	United States	73104
25	University of Oklahoma -OU Physicians	Oklahoma City	Oklahoma	United States	73104
26	Retina Vitreous Consultants	Pittsburgh	Pennsylvania	United States	15213
27	Associates in Ophthalmology Ltd	West Mifflin	Pennsylvania	United States	15122
28	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701
29	Brain B.Berger,MD,PA	Austin	Texas	United States	78705
30	Retina Research Center	Austin	Texas	United States	78705
31	Retina Consultants of Houston, PA	Houston	Texas	United States	77030
32	Medical Center Ophthalmology Associates	San Antonio	Texas	United States	78240
33	Rocky Mountain Retina Consultants	Salt Lake City	Utah	United States	84107
34	MC Comac Medical	Sofia		Bulgaria	1612
35	Fakultní nemocnice Hradec Králové, Ocni klinika	Hradec Kralove		Czech Republic	500 05
36	Fakultní nemocnice Hradec Králové, Nemocnicni lekarna	Hradec Kralove		Czech Republic	50005
37	Fakultni nemocnice Ostrava, lekarna	Ostrava - Poruba		Czech Republic	70852
38	Fakultni nemocnice Ostrava, Ocni klinika	Ostrava - Poruba		Czech Republic	70852
39	Fakultni nemocnice Kralovske Vinohrady, Oftalmologicka klinika	Praha 10		Czech Republic	10034
40	Fakultni nemocnice Kralovske Vinohrady, Ustavni lekarna	Praha 10		Czech Republic	10034
41	Universitätsklinikum Regensburg	Regensburg	Bavaria	Germany	93053
42	Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin	Berlin		Germany	12200
43	Universitaetsmedizin Goettingen	Goettingen		Germany	37075
44	Universitatsmedizin Mainz	Mainz		Germany	55131
45	Augenärzte am St. Franziskus-Hospital	Muenster		Germany	48145
46	Universitaetsklinikum Muenster	Muenster		Germany	48159
47	Knappschaftsklinikum GmbH	Sulzbach, Saar		Germany	66280
48	Universitatsklinikum Tubingen	Tubingen		Germany	72076
49	Semmelweis Egyetem, Szemészeti Klinika	Budapest		Hungary	1083
50	Bajcsy-Zsilinszky Korhaz, Szemeszet	Budapest		Hungary	1106
51	Budapest Retina Associates Kft.	Budapest		Hungary	1133
52	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, Szemklinika	Debrecen		Hungary	4032
53	Ganglion Orvosi Kozpont	Pecs		Hungary	7621
54	Csolnoky Ferenc Korhaz, Szemeszeti Osztaly	Veszprem		Hungary	8200
55	Hadassah Medical Organization, Hadassah Medical Center, Ein Karem	Jerusalem		Israel	91120
56	Meir Medical Center	Kfar Saba		Israel	44281
57	Rabin Medical Center, Beilinson Hospital	Petah Tikva		Israel	49100
58	Kaplan Medical Center	Rehovot		Israel	76100
59	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
60	Spitalul Clinic Republican	Chisinau		Moldova, Republic of	MD-2025
61	Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza Radeckiego We Wrocławiu, Klinika Okulistyki	Wroclaw		Poland	50-367
62	Med Life SA, Sectia Oftalmologie	Bucuresti		Romania	010719
63	Institutul National de Diabet, Nutritie si Boli Metabolice "N.C.Paulescu"	Bucuresti		Romania	020475

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: NCT01994291
• Other Study ID Numbers: B1261009; 2013-003147-27
• First Posted: Nov 25, 2013
• Last Update Posted: Oct 17, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Pfizer: Chemokine Antagonist; Diabetic Macular Edema; Diabetes; Diabetes Mellitus; Macular Edema; Diabetic Retinopathy; Anti-VEGF
• Additional relevant MeSH terms: Macular Edema; Edema; Ranibizumab

Study Results

Participant Flow

Pre-assignment Detail	In total, 199 participants were randomized, with 99 randomized to receive PF 04634817 200 mg and 99 to placebo + ranibizumab 0.3/0.5 mg. One participant was randomized but discontinued prior to dosing as no longer willing to participate.

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.
Period Title: Overall Study
STARTED	99	43	56
Received Treatment	99	43	56
COMPLETED	84	36	47
NOT COMPLETED	15	7	9

Baseline Characteristics

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Total
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Total of all reporting groups
Overall Participants	99	43	56	198
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.5 (8.8)	60.4 (7.5)	63.4 (8.4)	62.3 (8.4)
Sex: Female, Male (Count of Participants)
Female	40 40.4%	17 39.5%	18 32.1%	75 37.9%
Male	59 59.6%	26 60.5%	38 67.9%	123 62.1%

Outcome Measures

1. Primary Outcome

Title	Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA)
Description	Refraction and visual acuity were assessed through the BCVA obtained using the retro illuminated early treatment diabetic retinopathy study (ETDRS) charts. Distance visual acuity was expressed as an ETDRS score (number of letters correctly read).
Time Frame	Baseline (Day 0) and Week 12

Outcome Measure Data

Analysis Population Description

all subjects randomized and who had received at least one dose of randomized treatment and had at least one post-baseline measurement of BCVA.

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	87	38	53	91
Least Squares Mean (80% Confidence Interval) [Letters]	1.55	3.87	4.03	3.96

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg
	Comments	The null hypothesis was that the difference, in the mean change from baseline in BCVA in the PF-04634817 group,and the control group is less than or equal to -3 letters.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority was to be declared if the lower limit of the confidence interval for the mean difference at Week 12 is greater than -3.0 letters.
Statistical Test of Hypothesis	p-Value	0.1271
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	-2.32
	Confidence Interval	(2-Sided) 80%; -4.27 to -0.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.52
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.5 mg
	Comments	The null hypothesis was that the difference, in the mean change from baseline in BCVA in the PF-04634817 group,and the control group is less than or equal to -3 letters.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority was to be declared if the lower limit of the confidence interval for the mean difference at Week 12 is greater than -3.0 letters.
Statistical Test of Hypothesis	p-Value	0.0699
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	-2.48
	Confidence Interval	(2-Sided) 80%; -4.24 to -0.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.36
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg/0.5 mg
	Comments	The null hypothesis was that the difference, in the mean change from baseline in BCVA in the PF-04634817 group,and the control group is less than or equal to -3 letters.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non inferiority was to be declared if the lower limit of the confidence interval for the mean difference at Week 12 is greater than -3.0 letters.
Statistical Test of Hypothesis	p-Value	0.0399
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	-2.41
	Confidence Interval	(2-Sided) 80%; -3.91 to -0.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.17
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12
Description	Refraction and visual acuity were assessed through the BCVA obtained using the retro illuminated ETDRS charts. Distance visual acuity was expressed as an ETDRS score (number of letters correctly read).
Time Frame	Baseline (Day 0) and Week 12

Outcome Measure Data

Analysis Population Description

all subjects randomized and who had received at least one dose of randomized treatment and had at least one post-baseline measurement of BCVA.

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	87	38	53	91
Number [proportion of participants]	0.0690 0.1%	0.2105 0.5%	0.1132 0.2%	0.1538 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0218
	Comments
	Method	Barnard test
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.1416
	Confidence Interval	(2-Sided) 80%; -0.2483 to -0.0467
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.5 mg
	Comments	baseline in BCVA in the PF-04634817 group,and the control group is less than or equal to -3 letters.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4209
	Comments
	Method	Barnard test.
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.0442
	Confidence Interval	(2-Sided) 80%; -0.1217 to 0.0261
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg/0.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0778
	Comments
	Method	Barnard test.
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.0849
	Confidence Interval	(2-Sided) 80%; -0.1516 to -0.0168
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12
Description	A central reading center was used for the evaluation. A photographer or technician pre certified ("study certified") by the Central Reading Center ought to perform all optical coherence tomography (OCT) imaging. Use of a Spectralis or Cirrus OCT was acceptable.
Time Frame	Baseline (Day 0) and Week 12

Outcome Measure Data

Analysis Population Description

all subjects randomized and who had received at least one dose of randomized treatment and had at least one post-baseline measurement of BCVA.

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	83	36	43	79
Least Squares Mean (80% Confidence Interval) [microns]	1.73	-112.35	-64.09	-85.59

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	114.07
	Confidence Interval	(2-Sided) 80%; 88.56 to 139.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.84
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	65.81
	Confidence Interval	(2-Sided) 80%; 42.20 to 89.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 18.36
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg/0.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	87.32
	Confidence Interval	(2-Sided) 80%; 67.45 to 107.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 15.44
	Estimation Comments

4. Secondary Outcome

Title	Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12
Description	Fluorescein Angiography (FA) using certified digital systems was taken by a photographer who had been pre-certified ("study-certified") by the Central Reading Center. They were evaluated by the Central Reading Center.
Time Frame	Baseline (Day 0) and Week 12

Outcome Measure Data

Analysis Population Description

all subjects randomized and who had received at least one dose of randomized treatment and had at least one post-baseline measurement of BCVA.

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	86	36	50	86
Least Squares Mean (80% Confidence Interval) [mm^2]	1.02	-6.96	-5.32	-6.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	7.98
	Confidence Interval	(2-Sided) 80%; 6.13 to 9.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.44
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	6.34
	Confidence Interval	(2-Sided) 80%; 4.70 to 7.98
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.28
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg/0.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	7.07
	Confidence Interval	(2-Sided) 80%; 5.66 to 8.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.09
	Estimation Comments

5. Secondary Outcome

Title	Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12
Description	Stereo color fundus photographs using certified digital systems were taken by a photographer who had been pre-certified ("study certified") by the Central Reading Center. They were evaluated by the Central Reading Center.
Time Frame	Baseline (Day 0) and Week 12

Outcome Measure Data

Analysis Population Description

all subjects randomized and who had received at least one dose of randomized treatment and had at least one post-baseline measurement of BCVA.

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	82	36	44	80
Least Squares Mean (80% Confidence Interval) [Letters]	0.11	-0.23	-0.44	-0.35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0423
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 80%; 0.13 to 0.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.17
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 80%; 0.36 to 0.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg/0.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS means
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 80%; 0.30 to 0.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

6. Secondary Outcome

Title	Plasma Concentration of PF-04634817 up to Week 12
Time Frame	Week 0, Week 4, Week 8, and Week 12

Outcome Measure Data

Analysis Population Description

All subjects in the full analysis set (FAS) for whom a pharmacokinetic sample was obtained and analyzed. The FAS was defined as all subjects randomized and who had received at least one dose of randomized treatment and had at least one post-baseline measurement of BCVA.

Arm/Group Title	PF-04634817 200 mg QD
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.
Measure Participants	96
Week 0, Hour 2 (N = 91)	612.5 (61)
Week 4, Hour 0 (N = 88)	180.0 (81)
Week 4, Hour 2 (N = 87)	682.0 (61)
Week 8, Hour 0 (N = 90)	159.9 (68)
Week 8, Hour 2 (N = 89)	752.0 (57)
Week 12 (N = 86)	285.2 (105)

7. 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.
Time Frame	Week 0 to Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	99	43	56	99
Number of Participants with AEs	53 53.5%	32 74.4%	27 48.2%	59 29.8%
Number of Participants with SAEs	7 7.1%	2 4.7%	3 5.4%	5 2.5%

8. Other Pre-specified Outcome

Title	Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs
Description	Number of participants who met the categorical summary of post-baseline criteria at any time point, defined as: supine pulse rate <40 beats per minute (bpm) or >120 bpm; supine systolic blood pressure (SBP) ≥30 millimeters of mercury (mmHg) change from baseline in same posture; supine diastolic BP (DBP) ≥20 mmHg change from baseline in same posture; supine SBP <90 mmHg; supine DBP <50 mmHg.
Time Frame	Week -5 to Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	99	42	55	97
Absolute Supine SBP <90 mm Hg	1 1%	0 0%	0 0%	0 0%
Increase from Baseline in Supine SBP >=30 mm Hg	3 3%	4 9.3%	3 5.4%	7 3.5%
Increase from Baseline in Supine DBP >=20 mm Hg	2 2%	2 4.7%	2 3.6%	4 2%
Decrease from Baseline in Supine SBP >=30 mm Hg	3 3%	0 0%	2 3.6%	2 1%
Decrease from Baseline in Supine DBP >=20 mm Hg	2 2%	0 0%	0 0%	0 0%

9. Other Pre-specified Outcome

Title	Number of Participants With Laboratory Abnormalities
Description	The following laboratory parameters were analyzed for abnormalities at any time point: hematology (hemoglobin, hematocrit, red blood cell count (RBC), white blood cell count (WBC) with differential, and platelet count); blood chemistry (sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, albumin, calcium, total, direct and indirect bilirubin, gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), alkaline phosphatase, creatine phosphokinase (CPK), uric acid, amylase and lipase); follicle-stimulating hormone (FSH) (Weeks -5 to 0 only, for postmenopausal women who have been amenorrheic for at least 12 consecutive months prior to screening visit).
Time Frame	Week -5 to Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	99	42	55	97
Number [participants]	45 45.5%	19 44.2%	21 37.5%	40 20.2%

10. Other Pre-specified Outcome

Title	Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Description	ECG parameters included PR interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval greater than or equal to (>=)300 milliseconds (msec) or >=25% increase when baseline is greater than (>)200 msec and >=50% increase when baseline is less than or equal to (≤)200 msec; QRS interval >=200 msec or >=25% increase when baseline is greater than (>)200 msec and >=50% increase when baseline is less than or equal to (≤)200 msec; QT interval >=500 msec; and QTcF >=450 msec or >=30 msec increase. The number of participants with potentially clinically significant ECG findings at any visit were reported.
Time Frame	Week -5 to Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	99	43	56	99
QTcF Interval 450-<480 msec	13 13.1%	2 4.7%	4 7.1%	6 3%
QTcF Interval 480-<500 msec	1 1%	0 0%	0 0%	0 0%
QRS Interval >=50% increase from baseline	0 0%	1 2.3%	0 0%	1 0.5%
QTcF Interval 30-<60 msec increase from baseline	6 6.1%	2 4.7%	1 1.8%	3 1.5%

11. Other Pre-specified Outcome

Title	Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12
Description	The anterior biomicroscopy exam was done undilated in order to assess whether there was any anterior segment inflammation caused either by ranibizumab or PF-04634817.
Time Frame	Week -5 to Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	99	43	56	99
Improvement of findings in Lids	1 1%	0 0%	0 0%	0 0%
New finding (NF)/worsening of findings in Lids	1 1%	0 0%	0 0%	0 0%
Improvement of findings in conjunctiva palpebrae	0 0%	0 0%	0 0%	0 0%
NF/worsening of findings in conjunctiva palpebrae	0 0%	1 2.3%	0 0%	1 0.5%
Improvement of findings in conjunctiva bulbi	2 2%	0 0%	0 0%	0 0%
NF/worsening of findings in conjunctiva bulbi	0 0%	0 0%	0 0%	0 0%
Improvement of findings in sclera	0 0%	0 0%	0 0%	0 0%
NF/worsening of findings in sclera	0 0%	0 0%	0 0%	0 0%
Improvement of findings in cornea	1 1%	0 0%	0 0%	0 0%
NF/worsening of findings in cornea	0 0%	0 0%	0 0%	0 0%
Improvement of findings in anterior chamber	0 0%	0 0%	0 0%	0 0%
NF/worsening of findings in anterior chamber	0 0%	0 0%	0 0%	0 0%
Improvement of findings in iris	0 0%	0 0%	0 0%	0 0%
NF/worsening of findings in iris	0 0%	0 0%	0 0%	0 0%
Improvement of findings in lens	0 0%	0 0%	0 0%	0 0%
NF/worsening of findings in lens	0 0%	0 0%	1 1.8%	1 0.5%

12. Other Pre-specified Outcome

Title	Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye
Description	IOP was measured using Goldmann applanation tonometry. To maintain consistency, it was recommended that the same examiner ought to measure IOP with the same tonometer at each visit for a given subject. Intraocular pressure ought to be measured in the study eye approximately 30 minutes after intravitreal injection or masked sham therapy (performed by unmasked study team member).
Time Frame	Week -5 to Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	99	43	56	99
Mean (Standard Deviation) [mmHg]	2.5 (2.58)	6.0 (4.74)	3.0 (3.32)	4.3 (4.24)

13. Other Pre-specified Outcome

Title	Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8
Description	Ophthalmoscopy ought to be performed after pupillary dilation to examine the vitreous body, optic nerve head, macular and peripheral retina. All findings, including the presence or absence of vitreous inflammation, ought to be documented. All post-dose ophthalmoscopy assessments ought to be made immediately following the administration of ranibizumab or masked sham therapy.
Time Frame	Week -5 to Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PF-04634817 200 mg QD	Placebo QD + Ranibizumab 0.3 mg	Placebo QD + Ranibizumab 0.5 mg	Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Measure Participants	99	43	56	99
Improvement of findings in vitreous body	0 0%	0 0%	0 0%	0 0%
NF/worsening of findings in vitreous body	0 0%	0 0%	0 0%	0 0%
Improvement of findings in optic nerve head	0 0%	0 0%	0 0%	0 0%
NF/worsening of findings in optic nerve head	0 0%	0 0%	0 0%	0 0%
Improvement of findings in retina macula	0 0%	0 0%	0 0%	0 0%
NF/worsening of findings in retina macula	0 0%	0 0%	0 0%	0 0%
Improvement of findings in retina non-macula	0 0%	0 0%	0 0%	0 0%
NF/worsening of findings in retina non-macula	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Baseline to Week 12
Arm/Group Title	PF-04634817 200 mg QD		Placebo QD + Ranibizumab 0.3 mg		Placebo QD + Ranibizumab 0.5 mg
Arm/Group Description	Participants received 50 mg tablets of PF-04634817 and masked sham therapy.		Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.		Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.
All Cause Mortality
	PF-04634817 200 mg QD		Placebo QD + Ranibizumab 0.3 mg		Placebo QD + Ranibizumab 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PF-04634817 200 mg QD		Placebo QD + Ranibizumab 0.3 mg		Placebo QD + Ranibizumab 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/99 (7.1%)		2/43 (4.7%)		3/56 (5.4%)
Cardiac disorders
Aortic valve stenosis	1/99 (1%)		0/43 (0%)		0/56 (0%)
Cardiac failure	1/99 (1%)		0/43 (0%)		0/56 (0%)
Coronary artery disease	1/99 (1%)		0/43 (0%)		0/56 (0%)
Gastrointestinal disorders
Pancreatitis chronic	0/99 (0%)		0/43 (0%)		1/56 (1.8%)
Vomiting	1/99 (1%)		0/43 (0%)		0/56 (0%)
Infections and infestations
Paronychia	0/99 (0%)		0/43 (0%)		1/56 (1.8%)
Sepsis	1/99 (1%)		0/43 (0%)		0/56 (0%)
Injury, poisoning and procedural complications
Head injury	1/99 (1%)		0/43 (0%)		0/56 (0%)
Rib fracture	1/99 (1%)		0/43 (0%)		0/56 (0%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/99 (0%)		0/43 (0%)		1/56 (1.8%)
Hyperuricaemia	0/99 (0%)		1/43 (2.3%)		0/56 (0%)
Hypoglycaemia	1/99 (1%)		0/43 (0%)		0/56 (0%)
Nervous system disorders
Ischaemic stroke	1/99 (1%)		0/43 (0%)		0/56 (0%)
VIIth nerve paralysis	0/99 (0%)		0/43 (0%)		1/56 (1.8%)
Psychiatric disorders
Personality disorder	0/99 (0%)		1/43 (2.3%)		0/56 (0%)
Vascular disorders
Extremity necrosis	0/99 (0%)		0/43 (0%)		1/56 (1.8%)
Other (Not Including Serious) Adverse Events
	PF-04634817 200 mg QD		Placebo QD + Ranibizumab 0.3 mg		Placebo QD + Ranibizumab 0.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/99 (17.2%)		15/43 (34.9%)		7/56 (12.5%)
Eye disorders
Blepharitis	1/99 (1%)		3/43 (7%)		0/56 (0%)
Conjunctival haemorrhage	5/99 (5.1%)		1/43 (2.3%)		0/56 (0%)
Diabetic retinal oedema	4/99 (4%)		7/43 (16.3%)		3/56 (5.4%)
Eye irritation	6/99 (6.1%)		0/43 (0%)		0/56 (0%)
Retinal haemorrhage	0/99 (0%)		3/43 (7%)		0/56 (0%)
Vitreous haemorrhage	2/99 (2%)		3/43 (7%)		1/56 (1.8%)
Investigations
Intraocular pressure increased	0/99 (0%)		1/43 (2.3%)		3/56 (5.4%)
Nervous system disorders
Headache	3/99 (3%)		4/43 (9.3%)		0/56 (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.