search
Back to results

To Evaluate the Pharmacodynamics, Safety, and Pharmacokinetics of Pazopanib Drops in Adult Subjects With Neovascular AMD

Primary Purpose

Macular Degeneration

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pazopanib
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 angiogenesis, pazopanib,, age-related macular degeneration (AMD),, vascular endothelial growth factor (VEGF),, choroidal neovascularization (CNV),

Eligibility Criteria

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

Inclusion Criteria:

  • Age-related macular degeneration patients diagnosed with subfoveal choroidal neovascularization in the study eye, with all of the following characteristics required:

    • central subfield thickness > 300 microns on investigator-determined OCT (inclusive of subretinal fluid)
    • active subfoveal leakage as determined by investigator-determined fluorescein angiography
    • minimally classic or occult with no classic CNV lesion
    • lesion size no greater than 12 disc areas
    • CNV > 50% of lesion area
    • < 50% of lesion area with blood
    • = 25% of lesion area with fibrosis
  • Best-corrected ETDRS visual acuity in the study eye between 80 to 24 letters inclusive (approximately 20/25 and 20/320 or 4/5 to 4/63) at screening
  • Female subjects must be of non-childbearing potential.

Exclusion Criteria:

  • Additional eye disease in the study eye that could compromise best corrected visual acuity (i.e. glaucoma with documented visual field loss, clinically significant diabetic retinopathy, ischemic optic neuropathy, or retinitis pigmentosa).
  • CNV in the study eye due to other causes unrelated to age-related macular degeneration.
  • The presence of retinal angiomatous proliferation (RAP) in the study eye, as determined by the investigator (confirmation by indocyanine green angiography is not required).
  • Geographic atrophy involving the center of the fovea in the study eye.
  • Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation of the fundus for photographs, fluorescein angiography and OCT.
  • Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD.
  • More than one prior photodynamic therapy (PDT) treatment in the study eye.
  • PDT treatment in the study eye < 12 weeks prior to dosing.
  • Previous treatment in the study eye with ranibizumab (Lucentis) or bevacizumab (Avastin) without resolution of exudation (intraretinal and subretinal fluid as documented by OCT).
  • Use of any treatment, either approved or experimental, for AMD in the study eye within 60 days of first dose of investigational product.
  • Intraocular surgery in the study eye within 3 months of dosing.
  • Aphakia or total absence of the posterior capsule (Yttrium aluminum garnet (YAG) capsulotomy permitted) in the study eye.
  • History of vitrectomy in the study eye.
  • Use of topical ocular medications in the study eye within 7 days of first dose of investigational product or expected use of topical ocular medications during the treatment period, with the exception of artificial tears (refer to Section 9.1)
  • Active treatment in the fellow eye, with the exception of preservative-free artificial tears.
  • Current use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol).
  • Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of first dose.
  • An unwillingness to refrain from wearing contact lenses starting from the screening visit, through the follow-up visit

  • Medical history or condition:

    • Uncontrolled Diabetes Mellitus, with hemoglobin A1c (HbA1c) > 10%.
    • Myocardial infarction or stroke within 12 months of screening.
    • Active bleeding disorder.
    • Major surgery within 1 month of screening.
    • Hepatic impairment.
  • Uncontrolled hypertension

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm 1

Arm 2

Arm 3

Arm Description

Pazopanib eye drops formulation 5 mg/mL daily for 28 days

Pazopanib eye drop formulation 5mg/mL TID for 28 days

Pazopanib eye drop formulation 2mg/mL TID for 28 days

Outcomes

Primary Outcome Measures

Mean Change From Baseline in Central Retinal/Lesion Thickness (CRLT) as Measured by the Carl Zeiss Meditec Stratus Optical Coherence Tomography (OCT) Scanner at Day 29
CRLT was measured by the Carl Zeiss Meditec Stratus OCT scanner based on the manual measurement of the distance between the inner and outer retina, inclusive of subretinal fluid and any choroidal neovascularization (CNV) as measured in the central 1 millimeter (mm) area of the 7 mm Posterior Pole Scan. OCT scans/images were collected by trained and certified photographer and analyzed by investigator. Two datasets were used for analysis namely Last observation carried forward (LOCF) which included missing assessment for a participant who completed at least 7 days of pazopanib eye drop replaced by the last non-missing assessment post 7 days of pazopanib eye drop treatment. OC dataset included a missing assessment at any scheduled time was considered unevaluable and was not imputed. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.

Secondary Outcome Measures

Number of Participants With Complete Ophthalmic Examination Values of Potential Clinical Concern
A complete eye examination was performed to include the following: Examination of eyelids and lashes (including meibomian glands), Pupil, motility and confrontation visual field examination, Slit lamp evaluation of anterior ocular structures (including conjunctiva, tear film, cornea with fluorescein staining, anterior chamber, iris, lens, and anterior vitreous), intraocular pressure (IOP) measurement and Dilated Fundus Examination (Indirect ophthalmoscopy and slit lamp biomicroscopy). Data has been presented in a consolidated format for the total number of participants with values of potential clinical concern for complete ophthalmic examinations until Day 43.
Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern
Vital sign assessments included systolic blood pressure, diastolic blood pressure and heart rate. The potential clinical concern range for systolic blood pressure was <85 and > 160 millimeters of mercury, diastolic blood pressure <45 and > 100 millimeters of mercury, 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 findings at any visit were reported.
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings
Single 12-lead ECGs were to be obtained at each Day 15 and follow-up Day 43 using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and QTc intervals. ECG findings were defined as abnormal-not clinically significant (A-NCS) and abnormal-clinically significant (A-CS). Data has been presented for the number of participants with A-NCS and A-CS findings.
Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern
Clinical chemistry parameters assessed included blood urea nitrogen, potassium, calcium, albumin, creatinine, chloride, sodium, total protein, glucose, total carbon dioxide, aspartate amino transferase, alanine amino transferase, direct bilirubin, total bilirubin, alkaline phosphatase and hematology parameters assessed included platelet count, white blood cell count, red blood cell count, reticulocyte count, hemoglobin, mean corpuscle volume, mean corpuscle hemoglobin, mean corpuscle hemoglobin concentration, total neutrophils, lymphocytes, monocytes, eosinophils, basophils. Data has been presented for the number of participants with values high and low of potential clinical concern for clinical chemistry and hematology.
Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis
Urinalysis included analysis for urine occult blood, urine glucose, urine ketones and urine proteins via dipstick analysis. Data has been presented for number of participants with abnormal urinalysis results. Only categories with values have been presented.
Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events
An AE is defined as 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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. Data has been presented for number of participants with ocular and non-ocular adverse events and serious adverse event
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Number of Letter Read on Standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) Charts at Day 29
BCVA was measured in the study eye using the ETDRS grading charts consists of at least 24 to 78 letters placed at a test distance of 4 meters. There were 7 cut off points in visual acuity on ETDRS grading chart: 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. Grade 15 to 29 indicates no impairment in vision and grade -15 to -29 indicates worst impairment in vision. Analyses were done for two sub-efficacy-populations. One sub-efficacy population included all participants in the efficacy population with a YES for retinal angiomatous proliferation (RAP)/retinal choroidal anastomosis (RCA) NONE field from Digital angiography reading center (DARC) FA form in study eye. The other included all participants in the efficacy population with a YES for eligible field from DARC FA form in study eye. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline calculated as subtracting the Baseline value from the value at Day 29.
Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT
OCT was used for the determination of retinal morphology changes in the study eye which included assessments of cystoids spaces (cyst like spaces in the inner layers of the retina), subretinal fluid (an exudate between the retina and choroid from various sources including the vitreous cavity, subarachnoid space, or abnormal vessels) and pigment epithelial detachment (retinal pigment epithelium separates from the underlying Bruch's membrane due to the presence of blood, serous exudate, drusen, or a neovascular membrane). Data has been presented for number of participants with retinal morphology changes in the study eye at Day 29.
Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP)
Fundus photography involves capturing of images of the center of the very back inner wall of the eye - the retina, optic nerve, macula and main retinal blood vessels. The parameters assessment were heme subretinal hemorrhage (absence or presence at the location), heme intraretinal hemorrhage (absence or presence at the location), subretinal fluid (absence or presence at location), fibrosis (absence or presence at location), atrophy (absence or presence of atrophic changes) and pigment ((absence or presence at location). A protocol set of fundus photographs were obtained at Day 29. Images were read by the investigator for eligibility determination, and by a central reading center for determination of PD effect. Data has been presented for number of participants with changes in eye characteristics in the study eye at Day 29.
Change From Baseline in Neovascular Size, Total Lesion Size, Fluorescein Angiography (FA) Leakage Area of Measurement, FA Blood Area of Measurement as Measured by FA at Day 29
FA uses FP to capture images of injected dye circulating throughout the retinal blood vessels to assess leaking, swelling or circulation problems caused by various eye diseases like diabetic retinopathy and wet macular degeneration. The parameters assessed were CNV size, Classic CNV size, FA blood area of measurement, FA leakage area of measurement and total lesion size. A protocol fluorescein angiogram was to be obtained at Day 29. Images were evaluated by investigator for eligibility determination, and by a central reading center for determination of PD effect. Data has been presented for change from baseline in change in eye characteristics in the study eye at Day 29. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.
Plasma Pharmacokinetic Parameter Maximum Observed Concentration (Cmax)
Blood samples for analysis of plasma pazopanib concentrations were collected over 6 hours after an ocular dose of pazopanib on Day 15 or Day 22. PK analyses of plasma pazopanib concentration-time data were conducted using non-compartmental Model 200 (for extravascular administration) of WinNonlin Professional Edition version 5.2. Data has been presented for pharmacokinetic parameter Cmax at Day 15 and Day 22.
Plasma Pharmacokinetic Parameter Time of Occurrence of Cmax (Tmax)
Blood samples for analysis of plasma pazopanib concentrations were collected over 6 hours after an ocular dose of pazopanib on Day 15 or Day 22. PK analyses of plasma pazopanib concentration-time data were conducted using non-compartmental Model 200 (for extravascular administration) of WinNonlin Professional Edition version 5.2. Data has been presented for pharmacokinetic parameter tmax at Day 15 and Day 22.
Plasma Pharmacokinetic Parameter Area Under Concentration Time-curve From Time Zero to 6 Hours (AUC [0-6)]
Blood samples for analysis of plasma pazopanib concentrations were collected over 6 hours after an ocular dose of pazopanib on Day 15 or Day 22. PK analyses of plasma pazopanib concentration-time data were conducted using non-compartmental Model 200 (for extravascular administration) of WinNonlin Professional Edition version 5.2. Data has been presented for pharmacokinetic parameter AUC (0-6) at Day 15 and Day 22.

Full Information

First Posted
January 29, 2008
Last Updated
October 18, 2017
Sponsor
GlaxoSmithKline
search

1. Study Identification

Unique Protocol Identification Number
NCT00612456
Brief Title
To Evaluate the Pharmacodynamics, Safety, and Pharmacokinetics of Pazopanib Drops in Adult Subjects With Neovascular AMD
Official Title
A Double-masked, Randomized, Parallel-group Study to Investigate the Pharmacodynamics, Safety, and Systemic Pharmacokinetics of Pazopanib Drops, Administered for 28 Days to Adult Subjects With Neovascular Age-related Macular Degeneration.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
March 5, 2008 (Actual)
Primary Completion Date
January 1, 2009 (Actual)
Study Completion Date
June 17, 2009 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a 28 day study to evaluate the pharmacodynamic effect of pazopanib eye drops on the central retinal thickness of AMD patients
Detailed Description
Pazopanib has been formulated as an eye drop for the topical treatment of age-related macular degeneration (AMD). Safety, tolerability and pharmacokinetics have been evaluated in a first study conducted in healthy volunteers (MD7108238). In the present study, three dosing regimens of pazopanib eye drops, administered for 28 days, will be evaluated in subjects with occult or minimally classic subtypes of choroidal neovascularization due to AMD. This study is designed to measure pharmacological activity of topically administered pazopanib in target tissues (choroid and retina) of patients with AMD by weekly evaluation of central retinal thickness as measured by optical coherence tomography (OCT). Evaluation of efficacy will be performed on an exploratory basis by weekly measurement of visual acuity. The ocular and systemic safety and systemic pharmacokinetics of pazopanib treatment for 28 days will also be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Macular Degeneration
Keywords
angiogenesis, pazopanib,, age-related macular degeneration (AMD),, vascular endothelial growth factor (VEGF),, choroidal neovascularization (CNV),

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Pazopanib eye drops formulation 5 mg/mL daily for 28 days
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
Pazopanib eye drop formulation 5mg/mL TID for 28 days
Arm Title
Arm 3
Arm Type
Experimental
Arm Description
Pazopanib eye drop formulation 2mg/mL TID for 28 days
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Intervention Description
Pazopanib eye drops formulation
Primary Outcome Measure Information:
Title
Mean Change From Baseline in Central Retinal/Lesion Thickness (CRLT) as Measured by the Carl Zeiss Meditec Stratus Optical Coherence Tomography (OCT) Scanner at Day 29
Description
CRLT was measured by the Carl Zeiss Meditec Stratus OCT scanner based on the manual measurement of the distance between the inner and outer retina, inclusive of subretinal fluid and any choroidal neovascularization (CNV) as measured in the central 1 millimeter (mm) area of the 7 mm Posterior Pole Scan. OCT scans/images were collected by trained and certified photographer and analyzed by investigator. Two datasets were used for analysis namely Last observation carried forward (LOCF) which included missing assessment for a participant who completed at least 7 days of pazopanib eye drop replaced by the last non-missing assessment post 7 days of pazopanib eye drop treatment. OC dataset included a missing assessment at any scheduled time was considered unevaluable and was not imputed. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.
Time Frame
Baseline (Day -3 to -1) and Day 29
Secondary Outcome Measure Information:
Title
Number of Participants With Complete Ophthalmic Examination Values of Potential Clinical Concern
Description
A complete eye examination was performed to include the following: Examination of eyelids and lashes (including meibomian glands), Pupil, motility and confrontation visual field examination, Slit lamp evaluation of anterior ocular structures (including conjunctiva, tear film, cornea with fluorescein staining, anterior chamber, iris, lens, and anterior vitreous), intraocular pressure (IOP) measurement and Dilated Fundus Examination (Indirect ophthalmoscopy and slit lamp biomicroscopy). Data has been presented in a consolidated format for the total number of participants with values of potential clinical concern for complete ophthalmic examinations until Day 43.
Time Frame
Upto follow-up (Day 43)
Title
Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern
Description
Vital sign assessments included systolic blood pressure, diastolic blood pressure and heart rate. The potential clinical concern range for systolic blood pressure was <85 and > 160 millimeters of mercury, diastolic blood pressure <45 and > 100 millimeters of mercury, 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 findings at any visit were reported.
Time Frame
Up to follow up (Day 46)
Title
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings
Description
Single 12-lead ECGs were to be obtained at each Day 15 and follow-up Day 43 using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and QTc intervals. ECG findings were defined as abnormal-not clinically significant (A-NCS) and abnormal-clinically significant (A-CS). Data has been presented for the number of participants with A-NCS and A-CS findings.
Time Frame
Day 15 and follow-up (Day 43)
Title
Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern
Description
Clinical chemistry parameters assessed included blood urea nitrogen, potassium, calcium, albumin, creatinine, chloride, sodium, total protein, glucose, total carbon dioxide, aspartate amino transferase, alanine amino transferase, direct bilirubin, total bilirubin, alkaline phosphatase and hematology parameters assessed included platelet count, white blood cell count, red blood cell count, reticulocyte count, hemoglobin, mean corpuscle volume, mean corpuscle hemoglobin, mean corpuscle hemoglobin concentration, total neutrophils, lymphocytes, monocytes, eosinophils, basophils. Data has been presented for the number of participants with values high and low of potential clinical concern for clinical chemistry and hematology.
Time Frame
Up to follow-up Day 43
Title
Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis
Description
Urinalysis included analysis for urine occult blood, urine glucose, urine ketones and urine proteins via dipstick analysis. Data has been presented for number of participants with abnormal urinalysis results. Only categories with values have been presented.
Time Frame
Day 29 and follow-up (Day 43)
Title
Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events
Description
An AE is defined as 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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. Data has been presented for number of participants with ocular and non-ocular adverse events and serious adverse event
Time Frame
Up to follow-up (Day 43)
Title
Change From Baseline in Best Corrected Visual Acuity (BCVA) [Number of Letter Read on Standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) Charts at Day 29
Description
BCVA was measured in the study eye using the ETDRS grading charts consists of at least 24 to 78 letters placed at a test distance of 4 meters. There were 7 cut off points in visual acuity on ETDRS grading chart: 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. Grade 15 to 29 indicates no impairment in vision and grade -15 to -29 indicates worst impairment in vision. Analyses were done for two sub-efficacy-populations. One sub-efficacy population included all participants in the efficacy population with a YES for retinal angiomatous proliferation (RAP)/retinal choroidal anastomosis (RCA) NONE field from Digital angiography reading center (DARC) FA form in study eye. The other included all participants in the efficacy population with a YES for eligible field from DARC FA form in study eye. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline calculated as subtracting the Baseline value from the value at Day 29.
Time Frame
Baseline (Day -3 to -1) and Day 29
Title
Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT
Description
OCT was used for the determination of retinal morphology changes in the study eye which included assessments of cystoids spaces (cyst like spaces in the inner layers of the retina), subretinal fluid (an exudate between the retina and choroid from various sources including the vitreous cavity, subarachnoid space, or abnormal vessels) and pigment epithelial detachment (retinal pigment epithelium separates from the underlying Bruch's membrane due to the presence of blood, serous exudate, drusen, or a neovascular membrane). Data has been presented for number of participants with retinal morphology changes in the study eye at Day 29.
Time Frame
Day 29
Title
Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP)
Description
Fundus photography involves capturing of images of the center of the very back inner wall of the eye - the retina, optic nerve, macula and main retinal blood vessels. The parameters assessment were heme subretinal hemorrhage (absence or presence at the location), heme intraretinal hemorrhage (absence or presence at the location), subretinal fluid (absence or presence at location), fibrosis (absence or presence at location), atrophy (absence or presence of atrophic changes) and pigment ((absence or presence at location). A protocol set of fundus photographs were obtained at Day 29. Images were read by the investigator for eligibility determination, and by a central reading center for determination of PD effect. Data has been presented for number of participants with changes in eye characteristics in the study eye at Day 29.
Time Frame
Day 29
Title
Change From Baseline in Neovascular Size, Total Lesion Size, Fluorescein Angiography (FA) Leakage Area of Measurement, FA Blood Area of Measurement as Measured by FA at Day 29
Description
FA uses FP to capture images of injected dye circulating throughout the retinal blood vessels to assess leaking, swelling or circulation problems caused by various eye diseases like diabetic retinopathy and wet macular degeneration. The parameters assessed were CNV size, Classic CNV size, FA blood area of measurement, FA leakage area of measurement and total lesion size. A protocol fluorescein angiogram was to be obtained at Day 29. Images were evaluated by investigator for eligibility determination, and by a central reading center for determination of PD effect. Data has been presented for change from baseline in change in eye characteristics in the study eye at Day 29. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.
Time Frame
Baseline (Day -3 to -1) and Day 29
Title
Plasma Pharmacokinetic Parameter Maximum Observed Concentration (Cmax)
Description
Blood samples for analysis of plasma pazopanib concentrations were collected over 6 hours after an ocular dose of pazopanib on Day 15 or Day 22. PK analyses of plasma pazopanib concentration-time data were conducted using non-compartmental Model 200 (for extravascular administration) of WinNonlin Professional Edition version 5.2. Data has been presented for pharmacokinetic parameter Cmax at Day 15 and Day 22.
Time Frame
Day 15 and Day 22
Title
Plasma Pharmacokinetic Parameter Time of Occurrence of Cmax (Tmax)
Description
Blood samples for analysis of plasma pazopanib concentrations were collected over 6 hours after an ocular dose of pazopanib on Day 15 or Day 22. PK analyses of plasma pazopanib concentration-time data were conducted using non-compartmental Model 200 (for extravascular administration) of WinNonlin Professional Edition version 5.2. Data has been presented for pharmacokinetic parameter tmax at Day 15 and Day 22.
Time Frame
Day 15 and Day 22
Title
Plasma Pharmacokinetic Parameter Area Under Concentration Time-curve From Time Zero to 6 Hours (AUC [0-6)]
Description
Blood samples for analysis of plasma pazopanib concentrations were collected over 6 hours after an ocular dose of pazopanib on Day 15 or Day 22. PK analyses of plasma pazopanib concentration-time data were conducted using non-compartmental Model 200 (for extravascular administration) of WinNonlin Professional Edition version 5.2. Data has been presented for pharmacokinetic parameter AUC (0-6) at Day 15 and Day 22.
Time Frame
Day 15 and Day 22

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age-related macular degeneration patients diagnosed with subfoveal choroidal neovascularization in the study eye, with all of the following characteristics required: central subfield thickness > 300 microns on investigator-determined OCT (inclusive of subretinal fluid) active subfoveal leakage as determined by investigator-determined fluorescein angiography minimally classic or occult with no classic CNV lesion lesion size no greater than 12 disc areas CNV > 50% of lesion area < 50% of lesion area with blood = 25% of lesion area with fibrosis Best-corrected ETDRS visual acuity in the study eye between 80 to 24 letters inclusive (approximately 20/25 and 20/320 or 4/5 to 4/63) at screening Female subjects must be of non-childbearing potential. Exclusion Criteria: Additional eye disease in the study eye that could compromise best corrected visual acuity (i.e. glaucoma with documented visual field loss, clinically significant diabetic retinopathy, ischemic optic neuropathy, or retinitis pigmentosa). CNV in the study eye due to other causes unrelated to age-related macular degeneration. The presence of retinal angiomatous proliferation (RAP) in the study eye, as determined by the investigator (confirmation by indocyanine green angiography is not required). Geographic atrophy involving the center of the fovea in the study eye. Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation of the fundus for photographs, fluorescein angiography and OCT. Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD. More than one prior photodynamic therapy (PDT) treatment in the study eye. PDT treatment in the study eye < 12 weeks prior to dosing. Previous treatment in the study eye with ranibizumab (Lucentis) or bevacizumab (Avastin) without resolution of exudation (intraretinal and subretinal fluid as documented by OCT). Use of any treatment, either approved or experimental, for AMD in the study eye within 60 days of first dose of investigational product. Intraocular surgery in the study eye within 3 months of dosing. Aphakia or total absence of the posterior capsule (Yttrium aluminum garnet (YAG) capsulotomy permitted) in the study eye. History of vitrectomy in the study eye. Use of topical ocular medications in the study eye within 7 days of first dose of investigational product or expected use of topical ocular medications during the treatment period, with the exception of artificial tears (refer to Section 9.1) Active treatment in the fellow eye, with the exception of preservative-free artificial tears. Current use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol). Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of first dose. An unwillingness to refrain from wearing contact lenses starting from the screening visit, through the follow-up visit Medical history or condition: Uncontrolled Diabetes Mellitus, with hemoglobin A1c (HbA1c) > 10%. Myocardial infarction or stroke within 12 months of screening. Active bleeding disorder. Major surgery within 1 month of screening. Hepatic impairment. Uncontrolled hypertension
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
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
GSK Investigational Site
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
GSK Investigational Site
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
GSK Investigational Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95841
Country
United States
Facility Name
GSK Investigational Site
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33334
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
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46280
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
GSK Investigational Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
GSK Investigational Site
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49525
Country
United States
Facility Name
GSK Investigational Site
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States
Facility Name
GSK Investigational Site
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
GSK Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
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
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
GSK Investigational Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
GSK Investigational Site
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
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
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
GSK Investigational Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
GSK Investigational Site
City
Trieste
State/Province
Friuli-Venezia-Giulia
ZIP/Postal Code
34129
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
Firenze
State/Province
Toscana
ZIP/Postal Code
50134
Country
Italy
Facility Name
GSK Investigational Site
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

To Evaluate the Pharmacodynamics, Safety, and Pharmacokinetics of Pazopanib Drops in Adult Subjects With Neovascular AMD

We'll reach out to this number within 24 hrs