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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01994291
Recruitment Status : Terminated
First Posted : November 25, 2013
Results First Posted : October 17, 2016
Last Update Posted : October 17, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Macular Edema, Diabetic
Interventions Drug: Ranibizumab
Drug: Placebo
Drug: PF-04634817
Drug: Masked Sham Therapy
Enrollment 199
Recruitment Details  
Pre-assignment Details 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
Hide 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
Reason Not Completed
Adverse Event             4             1             3
Lost to Follow-up             1             1             0
Does not meet entrance criteria             1             0             0
Medication error without associated AE             1             0             1
Protocol Violation             1             0             0
Withdrawal by Subject             6             3             5
Other             1             2             0
Arm/Group Title PF-04634817 200 mg QD Placebo QD + Ranibizumab 0.3 mg Placebo QD + Ranibizumab 0.5 mg Total
Hide 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 Number of Baseline Participants 99 43 56 198
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 99 participants 43 participants 56 participants 198 participants
62.5  (8.8) 60.4  (7.5) 63.4  (8.4) 62.3  (8.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 99 participants 43 participants 56 participants 198 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%
1.Primary Outcome
Title Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 87 38 53 91
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Letters
1.55
(-2.21 to 5.30)
3.87
(0.09 to 7.65)
4.03
(0.17 to 7.90)
3.96
(0.28 to 7.64)
Hide 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 [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
2.Secondary Outcome
Title Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 87 38 53 91
Measure Type: Number
Unit of Measure: proportion of participants
0.0690 0.2105 0.1132 0.1538
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0218
Comments [Not Specified]
Method Barnard test
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.1416
Confidence Interval (2-Sided) 80%
-0.2483 to -0.0467
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.4209
Comments [Not Specified]
Method Barnard test.
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.0442
Confidence Interval (2-Sided) 80%
-0.1217 to 0.0261
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0778
Comments [Not Specified]
Method Barnard test.
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.0849
Confidence Interval (2-Sided) 80%
-0.1516 to -0.0168
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 83 36 43 79
Least Squares Mean (80% Confidence Interval)
Unit of Measure: microns
1.73
(-50.41 to 53.87)
-112.35
(-164.5 to -60.23)
-64.09
(-118.0 to -10.17)
-85.59
(-136.8 to -34.43)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
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 [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 86 36 50 86
Least Squares Mean (80% Confidence Interval)
Unit of Measure: mm^2
1.02
(-3.80 to 5.85)
-6.96
(-11.66 to -2.26)
-5.32
(-10.23 to -0.41)
-6.05
(-10.76 to -1.34)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 82 36 44 80
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Letters
0.11
(-0.44 to 0.66)
-0.23
(-0.76 to 0.31)
-0.44
(-1.00 to 0.12)
-0.35
(-0.89 to 0.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0423
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04634817 200 mg QD, Placebo QD + Ranibizumab 0.3 mg/0.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
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 [Not Specified]
6.Secondary Outcome
Title Plasma Concentration of PF-04634817 up to Week 12
Hide Description [Not Specified]
Time Frame Week 0, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Participants received 50 mg tablets of PF-04634817 and masked sham therapy.
Overall Number of Participants Analyzed 96
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram (ng)/milliliter (mL)
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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 99 43 56 99
Measure Type: Number
Unit of Measure: participants
Number of Participants with AEs 53 32 27 59
Number of Participants with SAEs 7 2 3 5
8.Other Pre-specified Outcome
Title Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 99 42 55 97
Measure Type: Number
Unit of Measure: participants
Absolute Supine SBP <90 mm Hg 1 0 0 0
Increase from Baseline in Supine SBP >=30 mm Hg 3 4 3 7
Increase from Baseline in Supine DBP >=20 mm Hg 2 2 2 4
Decrease from Baseline in Supine SBP >=30 mm Hg 3 0 2 2
Decrease from Baseline in Supine DBP >=20 mm Hg 2 0 0 0
9.Other Pre-specified Outcome
Title Number of Participants With Laboratory Abnormalities
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 99 42 55 97
Measure Type: Number
Unit of Measure: participants
45 19 21 40
10.Other Pre-specified Outcome
Title Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 99 43 56 99
Measure Type: Number
Unit of Measure: participants
QTcF Interval 450-<480 msec 13 2 4 6
QTcF Interval 480-<500 msec 1 0 0 0
QRS Interval >=50% increase from baseline 0 1 0 1
QTcF Interval 30-<60 msec increase from baseline 6 2 1 3
11.Other Pre-specified Outcome
Title Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 99 43 56 99
Measure Type: Number
Unit of Measure: participants
Improvement of findings in Lids 1 0 0 0
New finding (NF)/worsening of findings in Lids 1 0 0 0
Improvement of findings in conjunctiva palpebrae 0 0 0 0
NF/worsening of findings in conjunctiva palpebrae 0 1 0 1
Improvement of findings in conjunctiva bulbi 2 0 0 0
NF/worsening of findings in conjunctiva bulbi 0 0 0 0
Improvement of findings in sclera 0 0 0 0
NF/worsening of findings in sclera 0 0 0 0
Improvement of findings in cornea 1 0 0 0
NF/worsening of findings in cornea 0 0 0 0
Improvement of findings in anterior chamber 0 0 0 0
NF/worsening of findings in anterior chamber 0 0 0 0
Improvement of findings in iris 0 0 0 0
NF/worsening of findings in iris 0 0 0 0
Improvement of findings in lens 0 0 0 0
NF/worsening of findings in lens 0 0 1 1
12.Other Pre-specified Outcome
Title Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye
Hide 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
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Hide 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
Hide 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.
Overall Number of Participants Analyzed 99 43 56 99
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 99 43 56 99
Measure Type: Number
Unit of Measure: participants
Improvement of findings in vitreous body 0 0 0 0
NF/worsening of findings in vitreous body 0 0 0 0
Improvement of findings in optic nerve head 0 0 0 0
NF/worsening of findings in optic nerve head 0 0 0 0
Improvement of findings in retina macula 0 0 0 0
NF/worsening of findings in retina macula 0 0 0 0
Improvement of findings in retina non-macula 0 0 0 0
NF/worsening of findings in retina non-macula 0 0 0 0
Time Frame Baseline to Week 12
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PF-04634817 200 mg QD Placebo QD + Ranibizumab 0.3 mg Placebo QD + Ranibizumab 0.5 mg
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
PF-04634817 200 mg QD Placebo QD + Ranibizumab 0.3 mg Placebo QD + Ranibizumab 0.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/99 (7.07%)   2/43 (4.65%)   3/56 (5.36%) 
Cardiac disorders       
Aortic valve stenosis * 1  1/99 (1.01%)  0/43 (0.00%)  0/56 (0.00%) 
Cardiac failure * 1  1/99 (1.01%)  0/43 (0.00%)  0/56 (0.00%) 
Coronary artery disease * 1  1/99 (1.01%)  0/43 (0.00%)  0/56 (0.00%) 
Gastrointestinal disorders       
Pancreatitis chronic * 1  0/99 (0.00%)  0/43 (0.00%)  1/56 (1.79%) 
Vomiting * 1  1/99 (1.01%)  0/43 (0.00%)  0/56 (0.00%) 
Infections and infestations       
Paronychia * 1  0/99 (0.00%)  0/43 (0.00%)  1/56 (1.79%) 
Sepsis * 1  1/99 (1.01%)  0/43 (0.00%)  0/56 (0.00%) 
Injury, poisoning and procedural complications       
Head injury * 1  1/99 (1.01%)  0/43 (0.00%)  0/56 (0.00%) 
Rib fracture * 1  1/99 (1.01%)  0/43 (0.00%)  0/56 (0.00%) 
Metabolism and nutrition disorders       
Diabetic ketoacidosis * 1  0/99 (0.00%)  0/43 (0.00%)  1/56 (1.79%) 
Hyperuricaemia * 1  0/99 (0.00%)  1/43 (2.33%)  0/56 (0.00%) 
Hypoglycaemia * 1  1/99 (1.01%)  0/43 (0.00%)  0/56 (0.00%) 
Nervous system disorders       
Ischaemic stroke * 1  1/99 (1.01%)  0/43 (0.00%)  0/56 (0.00%) 
VIIth nerve paralysis * 1  0/99 (0.00%)  0/43 (0.00%)  1/56 (1.79%) 
Psychiatric disorders       
Personality disorder * 1  0/99 (0.00%)  1/43 (2.33%)  0/56 (0.00%) 
Vascular disorders       
Extremity necrosis * 1  0/99 (0.00%)  0/43 (0.00%)  1/56 (1.79%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PF-04634817 200 mg QD Placebo QD + Ranibizumab 0.3 mg Placebo QD + Ranibizumab 0.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/99 (17.17%)   15/43 (34.88%)   7/56 (12.50%) 
Eye disorders       
Blepharitis * 1  1/99 (1.01%)  3/43 (6.98%)  0/56 (0.00%) 
Conjunctival haemorrhage * 1  5/99 (5.05%)  1/43 (2.33%)  0/56 (0.00%) 
Diabetic retinal oedema * 1  4/99 (4.04%)  7/43 (16.28%)  3/56 (5.36%) 
Eye irritation * 1  6/99 (6.06%)  0/43 (0.00%)  0/56 (0.00%) 
Retinal haemorrhage * 1  0/99 (0.00%)  3/43 (6.98%)  0/56 (0.00%) 
Vitreous haemorrhage * 1  2/99 (2.02%)  3/43 (6.98%)  1/56 (1.79%) 
Investigations       
Intraocular pressure increased * 1  0/99 (0.00%)  1/43 (2.33%)  3/56 (5.36%) 
Nervous system disorders       
Headache * 1  3/99 (3.03%)  4/43 (9.30%)  0/56 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 18007181021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01994291    
Other Study ID Numbers: B1261009
2013-003147-27 ( EudraCT Number )
First Submitted: November 8, 2013
First Posted: November 25, 2013
Results First Submitted: July 5, 2016
Results First Posted: October 17, 2016
Last Update Posted: October 17, 2016