Macular Edema, Diabetic
Conditions
Keywords
Chemokine Antagonist, Diabetic Macular Edema, Diabetes, Diabetes Mellitus, Macular Edema, Diabetic Retinopathy, Anti-VEGF
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.
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.
Interventions
DRUGRanibizumab
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
DRUGPlacebo
Oral Placebo is provided in tablet form to match the 50mg dose of PF-04634817. Dose is 4 tablets each day for 12 weeks
DRUGPF-04634817
Four 50mg tablets PF-04634817 once a day for 12 weeks.
DRUGMasked Sham Therapy
Empty, needle-less syringe is used by the unmasked team once a month.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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. |
| Plasma Concentration of PF-04634817 up to Week 12 | Week 0, Week 4, Week 8, and Week 12 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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). |
Countries
Bulgaria, Czechia, Germany, Hungary, Israel, Moldova, Poland, Romania, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| PF-04634817 200 mg QD Participants received 50 mg tablets of PF-04634817 and masked sham therapy. | 99 |
| Placebo QD + Ranibizumab 0.3 mg Participants received Ranibizumab 0.3 mg intravitreal injection and matching placebo. | 43 |
| Placebo QD + Ranibizumab 0.5 mg Participants received Ranibizumab 0.5 mg intravitreal injection and matching placebo. | 56 |
| Total | 198 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 | 3 |
| Overall Study | Does not meet entrance criteria | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Medication error without associated AE | 1 | 0 | 1 |
| Overall Study | Other | 1 | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 3 | 5 |
Baseline characteristics
| Characteristic | PF-04634817 200 mg QD | Placebo QD + Ranibizumab 0.3 mg | Placebo QD + Ranibizumab 0.5 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 8.8 | 60.4 years STANDARD_DEVIATION 7.5 | 63.4 years STANDARD_DEVIATION 8.4 | 62.3 years STANDARD_DEVIATION 8.4 |
| Sex: Female, Male Female | 40 Participants | 17 Participants | 18 Participants | 75 Participants |
| Sex: Female, Male Male | 59 Participants | 26 Participants | 38 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 99 | 15 / 43 | 7 / 56 |
| serious Total, serious adverse events | 7 / 99 | 2 / 43 | 3 / 56 |
Outcome results
Primary
Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (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).
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PF-04634817 200 mg QD | Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA) | 1.55 Letters |
| Placebo QD + Ranibizumab 0.3 mg | Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA) | 3.87 Letters |
| Placebo QD + Ranibizumab 0.5 mg | Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA) | 4.03 Letters |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA) | 3.96 Letters |
Comparison: 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.p-value: 0.127180% CI: [-4.27, -0.37]Mixed Models Analysis
Comparison: 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.p-value: 0.069980% CI: [-4.24, -0.73]Mixed Models Analysis
Comparison: 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.p-value: 0.039980% CI: [-3.91, -0.91]Mixed Models Analysis
Secondary
Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at 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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PF-04634817 200 mg QD | Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12 | 1.73 microns |
| Placebo QD + Ranibizumab 0.3 mg | Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12 | -112.35 microns |
| Placebo QD + Ranibizumab 0.5 mg | Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12 | -64.09 microns |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12 | -85.59 microns |
p-value: <0.000180% CI: [88.56, 139.59]Mixed Models Analysis
p-value: 0.000480% CI: [42.2, 89.43]Mixed Models Analysis
p-value: <0.000180% CI: [67.45, 107.19]Mixed Models Analysis
Secondary
Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at 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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PF-04634817 200 mg QD | Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12 | 0.11 Letters |
| Placebo QD + Ranibizumab 0.3 mg | Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12 | -0.23 Letters |
| Placebo QD + Ranibizumab 0.5 mg | Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12 | -0.44 Letters |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12 | -0.35 Letters |
p-value: 0.042380% CI: [0.13, 0.55]ANCOVA
p-value: 0.000480% CI: [0.36, 0.75]ANCOVA
p-value: 0.000480% CI: [0.3, 0.63]ANCOVA
Secondary
Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at 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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PF-04634817 200 mg QD | Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12 | 1.02 mm^2 |
| Placebo QD + Ranibizumab 0.3 mg | Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12 | -6.96 mm^2 |
| Placebo QD + Ranibizumab 0.5 mg | Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12 | -5.32 mm^2 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12 | -6.05 mm^2 |
p-value: <0.000180% CI: [6.13, 9.83]ANCOVA
p-value: <0.000180% CI: [4.7, 7.98]ANCOVA
p-value: <0.000180% CI: [5.66, 8.48]ANCOVA
Secondary
Plasma Concentration of PF-04634817 up to Week 12
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | Plasma Concentration of PF-04634817 up to Week 12 | Week 12 (N = 86) | 285.2 nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 105 |
Secondary
Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at 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).
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04634817 200 mg QD | Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12 | 0.0690 proportion of participants |
| Placebo QD + Ranibizumab 0.3 mg | Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12 | 0.2105 proportion of participants |
| Placebo QD + Ranibizumab 0.5 mg | Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12 | 0.1132 proportion of participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12 | 0.1538 proportion of participants |
p-value: 0.021880% CI: [-0.2483, -0.0467]Barnard test
Comparison: baseline in BCVA in the PF-04634817 group,and the control group is less than or equal to -3 letters.p-value: 0.420980% CI: [-0.1217, 0.0261]Barnard test.
p-value: 0.077880% CI: [-0.1516, -0.0168]Barnard test.
Other Pre-specified
Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye
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
Population: The Safety Analysis Set was defined as all subjects who receive at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-04634817 200 mg QD | Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye | 2.5 mmHg | Standard Deviation 2.58 |
| Placebo QD + Ranibizumab 0.3 mg | Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye | 6.0 mmHg | Standard Deviation 4.74 |
| Placebo QD + Ranibizumab 0.5 mg | Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye | 3.0 mmHg | Standard Deviation 3.32 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye | 4.3 mmHg | Standard Deviation 4.24 |
Other Pre-specified
Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8
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
Population: The Safety Analysis Set was defined as all subjects who receive at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | 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 |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
Other Pre-specified
Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12
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
Population: The Safety Analysis Set was defined as all subjects who receive at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in anterior chamber | 0 participants |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in conjunctiva bulbi | 2 participants |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in cornea | 0 participants |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in lens | 0 participants |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in iris | 0 participants |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in cornea | 1 participants |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in lens | 0 participants |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in sclera | 0 participants |
| PF-04634817 200 mg QD | 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 |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in conjunctiva palpebrae | 0 participants |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in iris | 0 participants |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in sclera | 0 participants |
| PF-04634817 200 mg QD | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in Lids | 1 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in sclera | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in cornea | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in lens | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in cornea | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in anterior chamber | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in conjunctiva palpebrae | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in Lids | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in conjunctiva palpebrae | 1 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in lens | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in iris | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in conjunctiva bulbi | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in iris | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in sclera | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | New finding (NF)/worsening of findings in Lids | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in cornea | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in Lids | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | New finding (NF)/worsening of findings in Lids | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in conjunctiva palpebrae | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in conjunctiva bulbi | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in sclera | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in sclera | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in cornea | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in lens | 1 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in anterior chamber | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in iris | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in iris | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in lens | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in lens | 1 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in sclera | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | 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 |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in lens | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in iris | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in conjunctiva bulbi | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in conjunctiva palpebrae | 1 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in Lids | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in iris | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in conjunctiva palpebrae | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in cornea | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | New finding (NF)/worsening of findings in Lids | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in anterior chamber | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | Improvement of findings in cornea | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 | NF/worsening of findings in sclera | 0 participants |
Other Pre-specified
Number of Participants With Laboratory Abnormalities
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
Population: The Safety Analysis Set was defined as all subjects who receive at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04634817 200 mg QD | Number of Participants With Laboratory Abnormalities | 45 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Laboratory Abnormalities | 19 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Laboratory Abnormalities | 21 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Laboratory Abnormalities | 40 participants |
Other Pre-specified
Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs
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
Population: The Safety Analysis Set was defined as all subjects who receive at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04634817 200 mg QD | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Increase from Baseline in Supine DBP >=20 mm Hg | 2 participants |
| PF-04634817 200 mg QD | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Absolute Supine SBP <90 mm Hg | 1 participants |
| PF-04634817 200 mg QD | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Decrease from Baseline in Supine SBP >=30 mm Hg | 3 participants |
| PF-04634817 200 mg QD | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Increase from Baseline in Supine SBP >=30 mm Hg | 3 participants |
| PF-04634817 200 mg QD | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Decrease from Baseline in Supine DBP >=20 mm Hg | 2 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Increase from Baseline in Supine DBP >=20 mm Hg | 2 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Increase from Baseline in Supine SBP >=30 mm Hg | 4 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Decrease from Baseline in Supine SBP >=30 mm Hg | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Absolute Supine SBP <90 mm Hg | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Decrease from Baseline in Supine DBP >=20 mm Hg | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Decrease from Baseline in Supine DBP >=20 mm Hg | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Absolute Supine SBP <90 mm Hg | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Increase from Baseline in Supine SBP >=30 mm Hg | 3 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Increase from Baseline in Supine DBP >=20 mm Hg | 2 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Decrease from Baseline in Supine SBP >=30 mm Hg | 2 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Decrease from Baseline in Supine DBP >=20 mm Hg | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Decrease from Baseline in Supine SBP >=30 mm Hg | 2 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Increase from Baseline in Supine SBP >=30 mm Hg | 7 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Absolute Supine SBP <90 mm Hg | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs | Increase from Baseline in Supine DBP >=20 mm Hg | 4 participants |
Other Pre-specified
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
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
Population: The Safety Analysis Set was defined as all subjects who receive at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04634817 200 mg QD | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 450-<480 msec | 13 participants |
| PF-04634817 200 mg QD | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 480-<500 msec | 1 participants |
| PF-04634817 200 mg QD | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QRS Interval >=50% increase from baseline | 0 participants |
| PF-04634817 200 mg QD | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 30-<60 msec increase from baseline | 6 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 480-<500 msec | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QRS Interval >=50% increase from baseline | 1 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 30-<60 msec increase from baseline | 2 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 450-<480 msec | 2 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QRS Interval >=50% increase from baseline | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 480-<500 msec | 0 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 30-<60 msec increase from baseline | 1 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 450-<480 msec | 4 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 30-<60 msec increase from baseline | 3 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 480-<500 msec | 0 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QTcF Interval 450-<480 msec | 6 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings | QRS Interval >=50% increase from baseline | 1 participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
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
Population: The Safety Analysis Set was defined as all subjects who receive at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04634817 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Number of Participants with AEs | 53 participants |
| PF-04634817 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Number of Participants with SAEs | 7 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Number of Participants with SAEs | 2 participants |
| Placebo QD + Ranibizumab 0.3 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Number of Participants with AEs | 32 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Number of Participants with AEs | 27 participants |
| Placebo QD + Ranibizumab 0.5 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Number of Participants with SAEs | 3 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Number of Participants with AEs | 59 participants |
| Placebo QD + Ranibizumab 0.3 mg/0.5 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Number of Participants with SAEs | 5 participants |