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Dose Ranging Study of Pazopanib to Treat Neovascular Age-Related Macular Degeneration

Primary Purpose

Macular Degeneration

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
pazopanib eye drops
placebo
ranibizumab intravitreal injection
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Macular Degeneration focused on measuring ranibizumab, wet AMD, MD7110852, age related macular degeneration, age-related macular degeneration, macular degeneration, pazopanib

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Men and women aged ≥50 years.
  • Active subfoveal choroidal neovascularization (CNV) lesion secondary to AMD in study eye: Total lesion area ≤12 disc areas with CNV ≥50% total lesion area.
  • Anti-Vascular endothelial growth factor (VEGF) intravitreal injection experienced and in need of re-treatment.
  • Best-corrected visual acuity of at least 24 letters (equates to approximately 20/320 Snellen equivalents or better).

Exclusion Criteria:

  • Prior ocular investigational drug/device for choroidal neovascularization, photodynamic therapy, radiation, subfoveal or juxtafoveal focal laser photocoagulation.
  • Prior failure to anti-VEGF intravitreal injection therapy.
  • Recent ocular investigational drug/device for non-CNV condition.
  • Prior ocular surgeries (vitrectomy, scleral buckle, or glaucoma filtering/shunt surgery). Cataract surgery permitted if ≥3 months and has posterior chamber intraocular lens.
  • Center-fovea involvement of any of the following: fibrosis, atrophy, serous retinal pigment epithelial detachment, or retinal pigment epithelial tear.
  • CNV in either eye due to other causes.
  • Clinical evidence of diabetic retinopathy or diabetic macular edema.
  • Recent myocardial infarction or cerebrovascular accident.
  • Uncontrolled hypertension in spite of antihypertensive medications.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Active Comparator

Arm Label

investigational arm 1

investigational arm 2

investigational arm 3

investigational arm 4

investigational arm 5

placebo control arm

active open-label control arm

Arm Description

5 mg/mL pazopanib eye drops TID with allowance for as-needed ranibizumab injection

5 mg/mL pazopanib eye drops QID with allowance for as-needed ranibizumab injection

10 mg/mL pazopanib eye drops BID with allowance for as-needed ranibizumab injection

10 mg/mL pazopanib eye drops TID with allowance for as-needed ranibizumab injection

10 mg/mL pazopanib eye drops QID with allowance for as-needed ranibizumab injection

Placebo eye drops QID with allowance for as-needed ranibizumab injection

Ranibizumab intravitreal injection every 4 weeks

Outcomes

Primary Outcome Measures

Change From Baseline in Best-corrected Visual Acuity (BCVA) as Measured by the Number of Letters Read on the Early Treatment of Diabetic Retinopathy Study (ETDRS) Grading Charts at a Starting Distance of 4 Meters at Week 52
BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.

Secondary Outcome Measures

Percentage of Ranibizumab Re-injections Received Over 28 and 52 Weeks
The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection. Injection rate over 52 weeks was computed by taking the number of injections received divided by the number of visits for the participant. Likewise for 28 weeks it was estimated as the number of post baseline injections received divided by the number of post baseline visits at or before the week 28 visit.
Number of Participants With BCVA Over Time
BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters.
Number of Participants Analyzed for Visual Acuity (VA) Response Over Time
VA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters.The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. This outcome measure contains the number of participants who were analyzed for VA response.
Change From Baseline in Center Point Thickness (CPT) Over Time
CPT was the inner limiting membrane to the beginning of the retinal pigment epithelium (RPE) inclusive of SR fluid. The outer boundary included the outer segment of the photoreceptors and not included the RPE. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study. In amendment 3, inclusion criterion number 5 was revised to remove the required quantitative OCT component. OCT examination was used to supplement FA findings and provided qualitative (presence of SR and/or IR fluid) and quantitative (a CPT that is at least 250 microns) evidence of an active subfoveal lesion. Hence data for pre and post amendment have been provided separately.
Number of Participants That Met Criteria for Re-injection
The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection.
Change From Baseline in the Area of Choroidal Neovascularisation (CNV)
Choroidal neovascularisation is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Change From Baseline in the Area of the CNV Lesion Complex (i.e. CNV, Blood, PED, and Fibrosis)
CNV is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Change From Baseline in the Area of Fluorescein Leakage
Fluorescein angiograms was performed at the Screening, Week 12, Week 28, and Week 52 Visits. All images, including any that were performed at the investigator's medical discretion, were transferred to the FPRC. Fluorescein was injected intravenously according to usual clinic procedures. Dose response was also examined under different aspects of re-injection, such as time to first injection, the percentage of participants that required an injection by Week 28, as well as the estimation of the probability of reinjection. FA assessments of area of fluorescein leakage, CNV area and area of CNV lesion complex were also examined for dose differentiation.
Change in Area of Serous Sensory Retinal Detachment (SSRD)
This is an Optical coherence tomography (OCT) parameter used to manually measure thickness along any scan. OCT was performed at week 28 and week 52.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations
Opthalmicexaminations were done on Ocular alignment and motility, pupillary function, and visual fields by confrontation. Slit-lamp biomicroscopic examination of the anterior segment structure was performed. Fundus slit-lamp biomicroscopic examination, including use of accessory diagnostic lenses, to view the vitreous, retina (including posterior pole and periphery), macula, vasculature, and optic nerve was also performed. These examinations were performed on the study eye (SE) and the Fellow eye (FE). Participants with abnormal findings are listed here.
Summary of Intraocular Pressure Exam Findings
Intraocular pressure (IOP) measurement was done with Goldmann tonometer. Intraocular pressure was measured prior to dilating the pupil and, to account for diurnal variation, at approximately the same time of day for every visit.
Number of Participants With Vital Sign Values Outside of Clinical Concern Range
Vital signs including systolic and diastolic blood pressure and heart rate were measured throughout the study. Number of participants with vital signs outside of clinical concern Range were summarized. 'High' denotes above normal range and 'Low' denotes below normal range for all the categories. The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (<85 and >160 millimeter of mercury [mmHg]), diastolic blood pressure (<45 and >100 mmHg) and heart rate (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.
Summary of Abnormal Electrocardiogram (ECG) Findings
12-Lead ECGs were performed in triplicate and were obtained on Weeks 4 to Week 28 and Week 52. The on-treatment ECGs were used to ascertain any risk of QTc interval prolongation at extremely low pazopanib exposures compared to what was routinely observed in participants with cancer. The on-treatment ECG data collected from participants assigned to one of the control arms also provided ECG background rate data for participants not exposed to pazopanib. Participants with Clinically significant abnormal ECGs are included here.
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern
The Laboratory Parameters included Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Amino Transferase (AST), Calcium, Bicarbonate, Creatinine, Glucose, Hemoglobin, Lymphocytes, Platelet count, Potassium, Sodium, Thyroid Stimulating Hormone (TSH), Total Bilirubin, Total Neutrophils, Blood Urea Nitrogen (BUN) and White Blood Cell count (WBC). Number of participants with Laboratory outside of clinical concern Range were summarized here. Data of high and low from the clinical concern range has been provided here. Here 'High' denotes above normal range and 'Low' denotes below normal range for all the categories.
Number of Participants With Laboratory Data of Clinical Concern for Urine Protein
Urine Samples were collected from Day 1 to Week 28 and Week 52 for analyses. In this dipstick test, the level of protein in urine samples was recorded as negative (Neg), trace (tr), 1+, 2+, and 3+ (the plus sign increases with a higher level of proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). Neg indicated no proteinuria and 3+(high positive) indicated worst proteinuria.
Plasma Concentrations of Pazopanib
All participants in the eye drop containing arms had a single blood sample drawn for assessment of pazopanib plasma concentration at the Week 4, Week 24 and Week 24. The sample was drawn without restriction for the time interval between blood draw and the last dose of IP eye drops.

Full Information

First Posted
May 27, 2010
Last Updated
December 7, 2017
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT01134055
Brief Title
Dose Ranging Study of Pazopanib to Treat Neovascular Age-Related Macular Degeneration
Official Title
MD7110852, A Phase 2b Dose-Ranging Study of Pazopanib Eye Drops Versus Ranibizumab Intravitreal Injections for the Treatment of Neovascular Age-Related Macular Degeneration
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
June 1, 2010 (Actual)
Primary Completion Date
October 1, 2012 (Actual)
Study Completion Date
October 1, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine the safety and efficacy of different dosage regimens of pazopanib eye drops for the treatment of neovascular age-related macular degeneration.
Detailed Description
MD7110852 is a Phase 2b dose-ranging study designed to demonstrate the 1 year efficacy and safety of pazopanib eye drops for the treatment of neovascular age related macular degeneration (AMD) in subjects whose disease is currently managed with anti-VEGF (vascular endothelial growth factor) injection therapy. Eye drop regimens are double-masked with placebo eye drops and will have access to open-label ranibizumab intravitreal (IVT) injection if needed. The ranibizumab IVT injection every 4 weeks control arm is open-label.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Macular Degeneration
Keywords
ranibizumab, wet AMD, MD7110852, age related macular degeneration, age-related macular degeneration, macular degeneration, pazopanib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
510 (Actual)

8. Arms, Groups, and Interventions

Arm Title
investigational arm 1
Arm Type
Experimental
Arm Description
5 mg/mL pazopanib eye drops TID with allowance for as-needed ranibizumab injection
Arm Title
investigational arm 2
Arm Type
Experimental
Arm Description
5 mg/mL pazopanib eye drops QID with allowance for as-needed ranibizumab injection
Arm Title
investigational arm 3
Arm Type
Experimental
Arm Description
10 mg/mL pazopanib eye drops BID with allowance for as-needed ranibizumab injection
Arm Title
investigational arm 4
Arm Type
Experimental
Arm Description
10 mg/mL pazopanib eye drops TID with allowance for as-needed ranibizumab injection
Arm Title
investigational arm 5
Arm Type
Experimental
Arm Description
10 mg/mL pazopanib eye drops QID with allowance for as-needed ranibizumab injection
Arm Title
placebo control arm
Arm Type
Placebo Comparator
Arm Description
Placebo eye drops QID with allowance for as-needed ranibizumab injection
Arm Title
active open-label control arm
Arm Type
Active Comparator
Arm Description
Ranibizumab intravitreal injection every 4 weeks
Intervention Type
Drug
Intervention Name(s)
pazopanib eye drops
Intervention Description
A tyrosine kinase inhibitor of multiple receptors including vascular endothelial growth factor receptors and platelet-derived growth factor receptors.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
placebo eye drops
Intervention Type
Biological
Intervention Name(s)
ranibizumab intravitreal injection
Intervention Description
Humanized recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A
Primary Outcome Measure Information:
Title
Change From Baseline in Best-corrected Visual Acuity (BCVA) as Measured by the Number of Letters Read on the Early Treatment of Diabetic Retinopathy Study (ETDRS) Grading Charts at a Starting Distance of 4 Meters at Week 52
Description
BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Time Frame
Day 1 and 52 weeks
Secondary Outcome Measure Information:
Title
Percentage of Ranibizumab Re-injections Received Over 28 and 52 Weeks
Description
The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection. Injection rate over 52 weeks was computed by taking the number of injections received divided by the number of visits for the participant. Likewise for 28 weeks it was estimated as the number of post baseline injections received divided by the number of post baseline visits at or before the week 28 visit.
Time Frame
Up to 52 weeks
Title
Number of Participants With BCVA Over Time
Description
BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters.
Time Frame
Up to Week 52
Title
Number of Participants Analyzed for Visual Acuity (VA) Response Over Time
Description
VA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters.The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. This outcome measure contains the number of participants who were analyzed for VA response.
Time Frame
Week 52
Title
Change From Baseline in Center Point Thickness (CPT) Over Time
Description
CPT was the inner limiting membrane to the beginning of the retinal pigment epithelium (RPE) inclusive of SR fluid. The outer boundary included the outer segment of the photoreceptors and not included the RPE. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study. In amendment 3, inclusion criterion number 5 was revised to remove the required quantitative OCT component. OCT examination was used to supplement FA findings and provided qualitative (presence of SR and/or IR fluid) and quantitative (a CPT that is at least 250 microns) evidence of an active subfoveal lesion. Hence data for pre and post amendment have been provided separately.
Time Frame
Baseline and Week 52
Title
Number of Participants That Met Criteria for Re-injection
Description
The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection.
Time Frame
Up to Week 52
Title
Change From Baseline in the Area of Choroidal Neovascularisation (CNV)
Description
Choroidal neovascularisation is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Time Frame
Day 1, Week 28 and Week 52
Title
Change From Baseline in the Area of the CNV Lesion Complex (i.e. CNV, Blood, PED, and Fibrosis)
Description
CNV is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Time Frame
Day 1, Week 28 and Week 52
Title
Change From Baseline in the Area of Fluorescein Leakage
Description
Fluorescein angiograms was performed at the Screening, Week 12, Week 28, and Week 52 Visits. All images, including any that were performed at the investigator's medical discretion, were transferred to the FPRC. Fluorescein was injected intravenously according to usual clinic procedures. Dose response was also examined under different aspects of re-injection, such as time to first injection, the percentage of participants that required an injection by Week 28, as well as the estimation of the probability of reinjection. FA assessments of area of fluorescein leakage, CNV area and area of CNV lesion complex were also examined for dose differentiation.
Time Frame
Day 1, Week 28 and Week 52
Title
Change in Area of Serous Sensory Retinal Detachment (SSRD)
Description
This is an Optical coherence tomography (OCT) parameter used to manually measure thickness along any scan. OCT was performed at week 28 and week 52.
Time Frame
Day 1, Week 28 and Week 52
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.
Time Frame
Up to 52 Weeks
Title
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations
Description
Opthalmicexaminations were done on Ocular alignment and motility, pupillary function, and visual fields by confrontation. Slit-lamp biomicroscopic examination of the anterior segment structure was performed. Fundus slit-lamp biomicroscopic examination, including use of accessory diagnostic lenses, to view the vitreous, retina (including posterior pole and periphery), macula, vasculature, and optic nerve was also performed. These examinations were performed on the study eye (SE) and the Fellow eye (FE). Participants with abnormal findings are listed here.
Time Frame
Up to Week 52
Title
Summary of Intraocular Pressure Exam Findings
Description
Intraocular pressure (IOP) measurement was done with Goldmann tonometer. Intraocular pressure was measured prior to dilating the pupil and, to account for diurnal variation, at approximately the same time of day for every visit.
Time Frame
Up to week 52
Title
Number of Participants With Vital Sign Values Outside of Clinical Concern Range
Description
Vital signs including systolic and diastolic blood pressure and heart rate were measured throughout the study. Number of participants with vital signs outside of clinical concern Range were summarized. 'High' denotes above normal range and 'Low' denotes below normal range for all the categories. The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (<85 and >160 millimeter of mercury [mmHg]), diastolic blood pressure (<45 and >100 mmHg) and heart rate (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.
Time Frame
Up to Week 52
Title
Summary of Abnormal Electrocardiogram (ECG) Findings
Description
12-Lead ECGs were performed in triplicate and were obtained on Weeks 4 to Week 28 and Week 52. The on-treatment ECGs were used to ascertain any risk of QTc interval prolongation at extremely low pazopanib exposures compared to what was routinely observed in participants with cancer. The on-treatment ECG data collected from participants assigned to one of the control arms also provided ECG background rate data for participants not exposed to pazopanib. Participants with Clinically significant abnormal ECGs are included here.
Time Frame
Week 4, Week 28, Week 44 and Week 52
Title
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern
Description
The Laboratory Parameters included Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Amino Transferase (AST), Calcium, Bicarbonate, Creatinine, Glucose, Hemoglobin, Lymphocytes, Platelet count, Potassium, Sodium, Thyroid Stimulating Hormone (TSH), Total Bilirubin, Total Neutrophils, Blood Urea Nitrogen (BUN) and White Blood Cell count (WBC). Number of participants with Laboratory outside of clinical concern Range were summarized here. Data of high and low from the clinical concern range has been provided here. Here 'High' denotes above normal range and 'Low' denotes below normal range for all the categories.
Time Frame
Up to Week 52
Title
Number of Participants With Laboratory Data of Clinical Concern for Urine Protein
Description
Urine Samples were collected from Day 1 to Week 28 and Week 52 for analyses. In this dipstick test, the level of protein in urine samples was recorded as negative (Neg), trace (tr), 1+, 2+, and 3+ (the plus sign increases with a higher level of proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). Neg indicated no proteinuria and 3+(high positive) indicated worst proteinuria.
Time Frame
Day 1 to Week 28 and Week 52
Title
Plasma Concentrations of Pazopanib
Description
All participants in the eye drop containing arms had a single blood sample drawn for assessment of pazopanib plasma concentration at the Week 4, Week 24 and Week 24. The sample was drawn without restriction for the time interval between blood draw and the last dose of IP eye drops.
Time Frame
Week 4, Week 24 and Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women aged ≥50 years. Active subfoveal choroidal neovascularization (CNV) lesion secondary to AMD in study eye: Total lesion area ≤12 disc areas with CNV ≥50% total lesion area. Anti-Vascular endothelial growth factor (VEGF) intravitreal injection experienced and in need of re-treatment. Best-corrected visual acuity of at least 24 letters (equates to approximately 20/320 Snellen equivalents or better). Exclusion Criteria: Prior ocular investigational drug/device for choroidal neovascularization, photodynamic therapy, radiation, subfoveal or juxtafoveal focal laser photocoagulation. Prior failure to anti-VEGF intravitreal injection therapy. Recent ocular investigational drug/device for non-CNV condition. Prior ocular surgeries (vitrectomy, scleral buckle, or glaucoma filtering/shunt surgery). Cataract surgery permitted if ≥3 months and has posterior chamber intraocular lens. Center-fovea involvement of any of the following: fibrosis, atrophy, serous retinal pigment epithelial detachment, or retinal pigment epithelial tear. CNV in either eye due to other causes. Clinical evidence of diabetic retinopathy or diabetic macular edema. Recent myocardial infarction or cerebrovascular accident. Uncontrolled hypertension in spite of antihypertensive medications.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Peoria
State/Province
Arizona
ZIP/Postal Code
85381
Country
United States
Facility Name
GSK Investigational Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85014
Country
United States
Facility Name
GSK Investigational Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85020
Country
United States
Facility Name
GSK Investigational Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
GSK Investigational Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85710
Country
United States
Facility Name
GSK Investigational Site
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
GSK Investigational Site
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
GSK Investigational Site
City
Poway
State/Province
California
ZIP/Postal Code
92064
Country
United States
Facility Name
GSK Investigational Site
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
GSK Investigational Site
City
Golden
State/Province
Colorado
ZIP/Postal Code
80401
Country
United States
Facility Name
GSK Investigational Site
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
GSK Investigational Site
City
Winter Haven
State/Province
Florida
ZIP/Postal Code
33880
Country
United States
Facility Name
GSK Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
GSK Investigational Site
City
Leawood
State/Province
Kansas
ZIP/Postal Code
66211
Country
United States
Facility Name
GSK Investigational Site
City
Paducah
State/Province
Kentucky
ZIP/Postal Code
42001
Country
United States
Facility Name
GSK Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
GSK Investigational Site
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
GSK Investigational Site
City
Traverse City
State/Province
Michigan
ZIP/Postal Code
49686
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
GSK Investigational Site
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28803
Country
United States
Facility Name
GSK Investigational Site
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
GSK Investigational Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
GSK Investigational Site
City
Beachwood
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
GSK Investigational Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
Facility Name
GSK Investigational Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
GSK Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43212
Country
United States
Facility Name
GSK Investigational Site
City
Ashland
State/Province
Oregon
ZIP/Postal Code
97520
Country
United States
Facility Name
GSK Investigational Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
GSK Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
GSK Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
GSK Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
GSK Investigational Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
GSK Investigational Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
GSK Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
GSK Investigational Site
City
Silverdale
State/Province
Washington
ZIP/Postal Code
98383
Country
United States
Facility Name
GSK Investigational Site
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Facility Name
GSK Investigational Site
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2000
Country
Australia
Facility Name
GSK Investigational Site
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2150
Country
Australia
Facility Name
GSK Investigational Site
City
Melbourne
State/Province
Victoria
Country
Australia
Facility Name
GSK Investigational Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
GSK Investigational Site
City
Bruxelles
ZIP/Postal Code
1020
Country
Belgium
Facility Name
GSK Investigational Site
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
GSK Investigational Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 3N9
Country
Canada
Facility Name
GSK Investigational Site
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
V8V 4X3
Country
Canada
Facility Name
GSK Investigational Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Facility Name
GSK Investigational Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4V2
Country
Canada
Facility Name
GSK Investigational Site
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L4W 1W9
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
GSK Investigational Site
City
Aarhus
ZIP/Postal Code
DK-8000
Country
Denmark
Facility Name
GSK Investigational Site
City
Glostrup
Country
Denmark
Facility Name
GSK Investigational Site
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
GSK Investigational Site
City
Tuebingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
72076
Country
Germany
Facility Name
GSK Investigational Site
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
80336
Country
Germany
Facility Name
GSK Investigational Site
City
Bonn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53127
Country
Germany
Facility Name
GSK Investigational Site
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Facility Name
GSK Investigational Site
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04103
Country
Germany
Facility Name
GSK Investigational Site
City
Kiel
State/Province
Schleswig-Holstein
ZIP/Postal Code
24105
Country
Germany
Facility Name
GSK Investigational Site
City
Udine
State/Province
Friuli-Venezia-Giulia
ZIP/Postal Code
33100
Country
Italy
Facility Name
GSK Investigational Site
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
GSK Investigational Site
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20157
Country
Italy
Facility Name
GSK Investigational Site
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10122
Country
Italy
Facility Name
GSK Investigational Site
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
GSK Investigational Site
City
Aichi
ZIP/Postal Code
460-0011
Country
Japan
Facility Name
GSK Investigational Site
City
Aichi
ZIP/Postal Code
462-0825
Country
Japan
Facility Name
GSK Investigational Site
City
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
GSK Investigational Site
City
Chiba
ZIP/Postal Code
279-0021
Country
Japan
Facility Name
GSK Investigational Site
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
GSK Investigational Site
City
Fukushima
ZIP/Postal Code
960-1295
Country
Japan
Facility Name
GSK Investigational Site
City
Hokkaido
ZIP/Postal Code
001-0016
Country
Japan
Facility Name
GSK Investigational Site
City
Hokkaido
ZIP/Postal Code
060-8604
Country
Japan
Facility Name
GSK Investigational Site
City
Kagawa
ZIP/Postal Code
761-0793
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
101-8309
Country
Japan
Facility Name
GSK Investigational Site
City
Linköping
ZIP/Postal Code
SE-581 85
Country
Sweden
Facility Name
GSK Investigational Site
City
Stockholm
ZIP/Postal Code
SE-112 82
Country
Sweden
Facility Name
GSK Investigational Site
City
Uppsala
ZIP/Postal Code
SE-751 85
Country
Sweden
Facility Name
GSK Investigational Site
City
Örebro
ZIP/Postal Code
SE-701 85
Country
Sweden

12. IPD Sharing Statement

Learn more about this trial

Dose Ranging Study of Pazopanib to Treat Neovascular Age-Related Macular Degeneration

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