Trial Outcomes & Findings for 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 (NCT NCT01994291)

NCT ID: NCT01994291

Last Updated: 2016-10-17

Results Overview

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).

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 199 participants
• Primary outcome timeframe: Baseline (Day 0) and Week 12
• Results posted on: 2016-10-17

Participant Flow

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.

Participant milestones

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

Reasons for withdrawal

Measure	PF-04634817 200 mg QD Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.
Overall Study Adverse Event	4	1	3
Overall Study Lost to Follow-up	1	1	0
Overall Study Does not meet entrance criteria	1	0	0
Overall Study Medication error without associated AE	1	0	1
Overall Study Protocol Violation	1	0	0
Overall Study Withdrawal by Subject	6	3	5
Overall Study Other	1	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	PF-04634817 200 mg QD n=99 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=43 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=56 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Total n=198 Participants Total of all reporting groups
Age, Continuous	62.5 years STANDARD_DEVIATION 8.8 • n=5 Participants	60.4 years STANDARD_DEVIATION 7.5 • n=7 Participants	63.4 years STANDARD_DEVIATION 8.4 • n=5 Participants	62.3 years STANDARD_DEVIATION 8.4 • n=4 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	17 Participants n=7 Participants	18 Participants n=5 Participants	75 Participants n=4 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	26 Participants n=7 Participants	38 Participants n=5 Participants	123 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) and Week 12

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

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).

Outcome measures

Measure	PF-04634817 200 mg QD n=87 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=38 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=53 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=91 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA)	1.55 Letters Interval -2.21 to 5.3	3.87 Letters Interval 0.09 to 7.65	4.03 Letters Interval 0.17 to 7.9	3.96 Letters Interval 0.28 to 7.64

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 12

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

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).

Outcome measures

Measure	PF-04634817 200 mg QD n=87 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=38 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=53 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=91 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12	0.0690 proportion of participants Interval -2.21 to 5.3	0.2105 proportion of participants Interval 0.09 to 7.65	0.1132 proportion of participants Interval 0.17 to 7.9	0.1538 proportion of participants Interval 0.28 to 7.64

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 12

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

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.

Outcome measures

Measure	PF-04634817 200 mg QD n=83 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=36 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=43 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=79 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12	1.73 microns Interval -50.41 to 53.87	-112.35 microns Interval -164.5 to -60.23	-64.09 microns Interval -118.0 to -10.17	-85.59 microns Interval -136.8 to -34.43

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 12

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

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.

Outcome measures

Measure	PF-04634817 200 mg QD n=86 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=36 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=50 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=86 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12	1.02 mm^2 Interval -3.8 to 5.85	-6.96 mm^2 Interval -11.66 to -2.26	-5.32 mm^2 Interval -10.23 to -0.41	-6.05 mm^2 Interval -10.76 to -1.34

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 12

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

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.

Outcome measures

Measure	PF-04634817 200 mg QD n=82 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=36 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=44 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=80 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12	0.11 Letters Interval -0.44 to 0.66	-0.23 Letters Interval -0.76 to 0.31	-0.44 Letters Interval -1.0 to 0.12	-0.35 Letters Interval -0.89 to 0.19

SECONDARY outcome

Timeframe: Week 0, Week 4, Week 8, and Week 12

Population: 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.

Outcome measures

Measure	PF-04634817 200 mg QD n=96 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Plasma Concentration of PF-04634817 up to Week 12 Week 0, Hour 2 (N = 91)	612.5 nanogram (ng)/milliliter (mL) Geometric Coefficient of Variation 61	—	—	—
Plasma Concentration of PF-04634817 up to Week 12 Week 4, Hour 0 (N = 88)	180.0 nanogram (ng)/milliliter (mL) Geometric Coefficient of Variation 81	—	—	—
Plasma Concentration of PF-04634817 up to Week 12 Week 4, Hour 2 (N = 87)	682.0 nanogram (ng)/milliliter (mL) Geometric Coefficient of Variation 61	—	—	—
Plasma Concentration of PF-04634817 up to Week 12 Week 8, Hour 0 (N = 90)	159.9 nanogram (ng)/milliliter (mL) Geometric Coefficient of Variation 68	—	—	—
Plasma Concentration of PF-04634817 up to Week 12 Week 8, Hour 2 (N = 89)	752.0 nanogram (ng)/milliliter (mL) Geometric Coefficient of Variation 57	—	—	—
Plasma Concentration of PF-04634817 up to Week 12 Week 12 (N = 86)	285.2 nanogram (ng)/milliliter (mL) Geometric Coefficient of Variation 105	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0 to Week 16

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

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.

Outcome measures

Measure	PF-04634817 200 mg QD n=99 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=43 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=56 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=99 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Number of Participants with AEs	53 participants	32 participants	27 participants	59 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Number of Participants with SAEs	7 participants	2 participants	3 participants	5 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week -5 to Week 16

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

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.

Outcome measures

Measure	PF-04634817 200 mg QD n=99 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=42 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=55 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=97 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs Absolute Supine SBP <90 mm Hg	1 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs Increase from Baseline in Supine SBP >=30 mm Hg	3 participants	4 participants	3 participants	7 participants
Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs Increase from Baseline in Supine DBP >=20 mm Hg	2 participants	2 participants	2 participants	4 participants
Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs Decrease from Baseline in Supine SBP >=30 mm Hg	3 participants	0 participants	2 participants	2 participants
Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs Decrease from Baseline in Supine DBP >=20 mm Hg	2 participants	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week -5 to Week 16

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

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).

Outcome measures

Measure	PF-04634817 200 mg QD n=99 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=42 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=55 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=97 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Number of Participants With Laboratory Abnormalities	45 participants	19 participants	21 participants	40 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week -5 to Week 16

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

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.

Outcome measures

Measure	PF-04634817 200 mg QD n=99 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=43 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=56 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=99 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QTcF Interval 450-<480 msec	13 participants	2 participants	4 participants	6 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QTcF Interval 480-<500 msec	1 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QRS Interval >=50% increase from baseline	0 participants	1 participants	0 participants	1 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QTcF Interval 30-<60 msec increase from baseline	6 participants	2 participants	1 participants	3 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week -5 to Week 16

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

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.

Outcome measures

Measure	PF-04634817 200 mg QD n=99 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=43 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=56 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=99 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 Improvement of findings in Lids	1 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 New finding (NF)/worsening of findings in Lids	1 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 Improvement of findings in conjunctiva palpebrae	0 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 NF/worsening of findings in conjunctiva palpebrae	0 participants	1 participants	0 participants	1 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 NF/worsening of findings in conjunctiva bulbi	0 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 Improvement of findings in sclera	0 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 NF/worsening of findings in sclera	0 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 Improvement of findings in cornea	1 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 Improvement of findings in anterior chamber	0 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 NF/worsening of findings in anterior chamber	0 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 Improvement of findings in iris	0 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 NF/worsening of findings in iris	0 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 Improvement of findings in lens	0 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 NF/worsening of findings in lens	0 participants	0 participants	1 participants	1 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 Improvement of findings in conjunctiva bulbi	2 participants	0 participants	0 participants	0 participants
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 NF/worsening of findings in cornea	0 participants	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week -5 to Week 16

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

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).

Outcome measures

Measure	PF-04634817 200 mg QD n=99 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=43 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=56 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=99 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye	2.5 mmHg Standard Deviation 2.58	6.0 mmHg Standard Deviation 4.74	3.0 mmHg Standard Deviation 3.32	4.3 mmHg Standard Deviation 4.24

OTHER_PRE_SPECIFIED outcome

Timeframe: Week -5 to Week 16

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

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.

Outcome measures

Measure	PF-04634817 200 mg QD n=99 Participants Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=43 Participants Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=56 Participants Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.3 mg/0.5 mg n=99 Participants Participants received Ranibizumab 0.3 mg/0.5 mg intravitreal injection and matching placebo.
Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 Improvement of findings in vitreous body	0 participants	0 participants	0 participants	0 participants
Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 NF/worsening of findings in vitreous body	0 participants	0 participants	0 participants	0 participants
Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 Improvement of findings in retina macula	0 participants	0 participants	0 participants	0 participants
Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 Improvement of findings in retina non-macula	0 participants	0 participants	0 participants	0 participants
Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 Improvement of findings in optic nerve head	0 participants	0 participants	0 participants	0 participants
Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 NF/worsening of findings in optic nerve head	0 participants	0 participants	0 participants	0 participants
Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 NF/worsening of findings in retina macula	0 participants	0 participants	0 participants	0 participants
Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 NF/worsening of findings in retina non-macula	0 participants	0 participants	0 participants	0 participants

Adverse Events

PF-04634817 200 mg QD

Serious events: 7 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo QD + Ranibizumab 0.3 mg

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Placebo QD + Ranibizumab 0.5 mg

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	PF-04634817 200 mg QD n=99 participants at risk Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=43 participants at risk Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=56 participants at risk Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.
Cardiac disorders Aortic valve stenosis	1.0% 1/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Cardiac disorders Cardiac failure	1.0% 1/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Cardiac disorders Coronary artery disease	1.0% 1/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Gastrointestinal disorders Pancreatitis chronic	0.00% 0/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	1.8% 1/56 • Baseline to Week 12
Gastrointestinal disorders Vomiting	1.0% 1/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Infections and infestations Paronychia	0.00% 0/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	1.8% 1/56 • Baseline to Week 12
Infections and infestations Sepsis	1.0% 1/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Injury, poisoning and procedural complications Head injury	1.0% 1/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Injury, poisoning and procedural complications Rib fracture	1.0% 1/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	1.8% 1/56 • Baseline to Week 12
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/99 • Baseline to Week 12	2.3% 1/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Metabolism and nutrition disorders Hypoglycaemia	1.0% 1/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Nervous system disorders Ischaemic stroke	1.0% 1/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Nervous system disorders VIIth nerve paralysis	0.00% 0/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	1.8% 1/56 • Baseline to Week 12
Psychiatric disorders Personality disorder	0.00% 0/99 • Baseline to Week 12	2.3% 1/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Vascular disorders Extremity necrosis	0.00% 0/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	1.8% 1/56 • Baseline to Week 12

Other adverse events

Measure	PF-04634817 200 mg QD n=99 participants at risk Participants received 50 mg tablets of PF-04634817 and masked sham therapy.	Placebo QD + Ranibizumab 0.3 mg n=43 participants at risk Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo.	Placebo QD + Ranibizumab 0.5 mg n=56 participants at risk Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo.
Eye disorders Blepharitis	1.0% 1/99 • Baseline to Week 12	7.0% 3/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Eye disorders Conjunctival haemorrhage	5.1% 5/99 • Baseline to Week 12	2.3% 1/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Eye disorders Diabetic retinal oedema	4.0% 4/99 • Baseline to Week 12	16.3% 7/43 • Baseline to Week 12	5.4% 3/56 • Baseline to Week 12
Eye disorders Eye irritation	6.1% 6/99 • Baseline to Week 12	0.00% 0/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Eye disorders Retinal haemorrhage	0.00% 0/99 • Baseline to Week 12	7.0% 3/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12
Eye disorders Vitreous haemorrhage	2.0% 2/99 • Baseline to Week 12	7.0% 3/43 • Baseline to Week 12	1.8% 1/56 • Baseline to Week 12
Investigations Intraocular pressure increased	0.00% 0/99 • Baseline to Week 12	2.3% 1/43 • Baseline to Week 12	5.4% 3/56 • Baseline to Week 12
Nervous system disorders Headache	3.0% 3/99 • Baseline to Week 12	9.3% 4/43 • Baseline to Week 12	0.00% 0/56 • Baseline to Week 12

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 18007181021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER