Macular Degeneration
Conditions
Keywords
angiogenesis, pazopanib,, age-related macular degeneration (AMD),, vascular endothelial growth factor (VEGF),, choroidal neovascularization (CNV),
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.
Interventions
DRUGPazopanib
Pazopanib eye drops formulation
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline (Day -3 to -1) and 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Up to follow up (Day 46) | 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 | Day 15 and follow-up (Day 43) | 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 | Up to follow-up Day 43 | 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 | Day 29 and follow-up (Day 43) | 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 | Up to follow-up (Day 43) | 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 | Baseline (Day -3 to -1) and 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 Complete Ophthalmic Examination Values of Potential Clinical Concern | Upto follow-up (Day 43) | 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 Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Day 29 | 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 | Baseline (Day -3 to -1) and 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) | Day 15 and Day 22 | 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) | Day 15 and Day 22 | 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)] | Day 15 and Day 22 | 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. |
| Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Day 29 | 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. |
Countries
Australia, Belgium, Italy, United States
Participant flow
Recruitment details
This study was conducted at 22 centers in the United States, Belgium, Italy and Australia between 18 February 2008 and 27 January 2009. A total of 70 participants with Age-related macular degeneration (AMD) were randomized to the study.
Participants by arm
| Arm | Count |
|---|---|
| Pazopanib 5 mg/mL TID Eligible participants received Pazopanib eye drops topically at a dose of 5 mg/mL TID for 28 days. Participants were instructed to administer drops with a 6-hour interval between daily doses.. | 27 |
| Pazopanib 2 mg/mL TID Eligible participants received Pazopanib eye drops topically at a dose of 2 mg/mL TID for 28 days. Participants were instructed to administer drops with a 6-hour interval between daily doses. | 27 |
| Pazopanib 5 mg/mL Once Daily Eligible participants received Pazopanib eye drops topically at a dose of 5 mg/mL once daily for 28 days. Participants were instructed to administer drops with a 6-hour interval between daily doses. | 16 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Pazopanib 5 mg/mL TID | Pazopanib 2 mg/mL TID | Pazopanib 5 mg/mL Once Daily | Total |
|---|---|---|---|---|
| Age, Customized 57 to 88 years | 27 Participants | 27 Participants | 16 Participants | 70 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 27 Participants | 16 Participants | 70 Participants |
| Sex: Female, Male Female | 20 Participants | 14 Participants | 9 Participants | 43 Participants |
| Sex: Female, Male Male | 7 Participants | 13 Participants | 7 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 | 0 / 16 |
| other Total, other adverse events | 7 / 27 | 1 / 27 | 3 / 16 |
| serious Total, serious adverse events | 0 / 27 | 1 / 27 | 0 / 16 |
Outcome results
Primary
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.
Time frame: Baseline (Day -3 to -1) and Day 29
Population: Pharmacodynamics (PD) parameters population comprised of all participants in the Safety Population and had Choroidal Neovascularization (CNV) present as detected by Fluorescein Angiography (FA). LOCF and OC dataset were used for analysis. Only those participants with data available at the indicated time point were included for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pazopanib 5 mg/mL TID | 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 as measued by OCT, LOCF data | 7.5 Microns | Standard Deviation 110.34 |
| Pazopanib 5 mg/mL TID | 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 as measued by OCT, OC data | 7.5 Microns | Standard Deviation 110.34 |
| Pazopanib 2 mg/mL TID | 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 as measued by OCT, LOCF data | 10.0 Microns | Standard Deviation 83.78 |
| Pazopanib 2 mg/mL TID | 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 as measued by OCT, OC data | 3.0 Microns | Standard Deviation 85.16 |
| Pazopanib 5 mg/mL Once Daily | 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 as measued by OCT, OC data | 9.1 Microns | Standard Deviation 69.12 |
| Pazopanib 5 mg/mL Once Daily | 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 as measued by OCT, LOCF data | 31.2 Microns | Standard Deviation 85.72 |
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.624195% CI: [-31.05, 42.71]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.731595% CI: [-26.52, 50.26]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.621295% CI: [-31.65, 43.18]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.598795% CI: [-36.44, 46.84]ANCOVA
Comparison: LOCF Data excluding potential one outlier participant. Comparison between Baseline value and Day 29 value.p-value: 0.48295% CI: [-37.28, 35.64]ANCOVA
Comparison: LOCF Data excluding potential one outlier participant. Comparison between Baseline value and Day 29 value.p-value: 0.856295% CI: [-17.33, 57.13]ANCOVA
Comparison: OC Data excluding potential one outlier participant. Comparison between Baseline value and Day 29 value.p-value: 0.48895% CI: [-37.46, 36.35]ANCOVA
Comparison: OC Data excluding potential one outlier participant. Comparison between Baseline value and Day 29 value.p-value: 0.755695% CI: [-26.38, 54.32]ANCOVA
Secondary
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.
Time frame: Baseline (Day -3 to -1) and Day 29
Population: Efficacy population comprised of all participants in the Safety Population who completed at least 7 days of pazopanib eye drop treatment and provided VA measurements and had CNV present as detected by FA. Only those participants available at the specified time points were included for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pazopanib 5 mg/mL TID | 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 | YES for RAP/RCA NONE field from DARC FA at Day 29 | 4.8 Scores on scale | Standard Deviation 5.67 |
| Pazopanib 5 mg/mL TID | 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 at Day 29 | 4.3 Scores on scale | Standard Deviation 5.95 |
| Pazopanib 5 mg/mL TID | 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 | YES for eligible field from DARC FA form at Day 29 | 3.5 Scores on scale | Standard Deviation 5.26 |
| Pazopanib 2 mg/mL TID | 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 | YES for RAP/RCA NONE field from DARC FA at Day 29 | 1.7 Scores on scale | Standard Deviation 7.43 |
| Pazopanib 2 mg/mL TID | 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 at Day 29 | 0.8 Scores on scale | Standard Deviation 8.38 |
| Pazopanib 2 mg/mL TID | 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 | YES for eligible field from DARC FA form at Day 29 | 0.8 Scores on scale | Standard Deviation 7.39 |
| Pazopanib 5 mg/mL Once Daily | 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 at Day 29 | 0.0 Scores on scale | Standard Deviation 2.05 |
| Pazopanib 5 mg/mL Once Daily | 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 | YES for eligible field from DARC FA form at Day 29 | 0.3 Scores on scale | Standard Deviation 1.38 |
| Pazopanib 5 mg/mL Once Daily | 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 | YES for RAP/RCA NONE field from DARC FA at Day 29 | -0.1 Scores on scale | Standard Deviation 2.13 |
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.001595% CI: [1.74, 6.91]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.592195% CI: [-2.05, 3.57]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.964695% CI: [-3.89, 4.07]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.000395% CI: [2.32, 7.19]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.220895% CI: [-1.02, 4.3]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.984795% CI: [-3.9, 3.83]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.014295% CI: [0.75, 6.31]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.554795% CI: [-2.02, 3.71]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value.p-value: 0.911495% CI: [-4.37, 4.88]ANCOVA
Secondary
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.
Time frame: Baseline (Day -3 to -1) and Day 29
Population: PD Parameter Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pazopanib 5 mg/mL TID | 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 leakage area of measurement at Day 29 | 0.8 millimeters | Standard Deviation 1.77 |
| Pazopanib 5 mg/mL TID | 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 blood area of measurement at Day 29 | -0.2 millimeters | Standard Deviation 0.75 |
| Pazopanib 5 mg/mL TID | 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 | CNV size at Day 29 | 0.6 millimeters | Standard Deviation 1.67 |
| Pazopanib 5 mg/mL TID | 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 | Classic CNV size at Day 29 | 0.2 millimeters | Standard Deviation 0.9 |
| Pazopanib 5 mg/mL TID | 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 | Total lesion size | 0.5 millimeters | Standard Deviation 1.57 |
| Pazopanib 2 mg/mL TID | 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 blood area of measurement at Day 29 | 1.0 millimeters | Standard Deviation 1.87 |
| Pazopanib 2 mg/mL TID | 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 | CNV size at Day 29 | 0.44 millimeters | Standard Deviation 2.04 |
| Pazopanib 2 mg/mL TID | 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 | Classic CNV size at Day 29 | 1.5 millimeters | Standard Deviation 1.62 |
| Pazopanib 2 mg/mL TID | 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 leakage area of measurement at Day 29 | 0.8 millimeters | Standard Deviation 2.06 |
| Pazopanib 2 mg/mL TID | 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 | Total lesion size | 1.2 millimeters | Standard Deviation 2.37 |
| Pazopanib 5 mg/mL Once Daily | 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 | Total lesion size | 0.7 millimeters | Standard Deviation 1.86 |
| Pazopanib 5 mg/mL Once Daily | 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 leakage area of measurement at Day 29 | 0.6 millimeters | Standard Deviation 1.88 |
| Pazopanib 5 mg/mL Once Daily | 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 | CNV size at Day 29 | 0.7 millimeters | Standard Deviation 1.96 |
| Pazopanib 5 mg/mL Once Daily | 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 blood area of measurement at Day 29 | 0.4 millimeters | Standard Deviation 0.82 |
| Pazopanib 5 mg/mL Once Daily | 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 | Classic CNV size at Day 29 | 0.7 millimeters | Standard Deviation 0.81 |
Comparison: Comparison between Baseline value and Day 29 value for FA Leakage Area of measurement.p-value: 0.053495% CI: [-0.01, 1.53]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for FA Leakage Area of measurement.p-value: 0.050895% CI: [0, 1.64]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for FA Leakage Area of measurement.p-value: 0.314195% CI: [-0.6, 1.83]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for FA Blood Area of measurement.p-value: 0.601895% CI: [-1.04, 0.62]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for FA Blood Area of measurement.p-value: 0.050995% CI: [0, 2]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for FA Blood Area of measurement.p-value: 0.397695% CI: [-0.7, 1.68]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for Total Lesion sizep-value: 0.24195% CI: [-0.32, 1.23]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for Total Lesion sizep-value: 0.003295% CI: [0.44, 2.09]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for Total Lesion sizep-value: 0.318595% CI: [-0.58, 1.75]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for CNV Sizep-value: 0.107495% CI: [-0.14, 1.37]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for CNV Sizep-value: 0.040395% CI: [0.04, 1.65]ANCOVA
Comparison: Comparison between Baseline value and Day 29 value for CNV Sizep-value: 0.24995% CI: [-0.5, 1.88]ANCOVA
Secondary
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.
Time frame: Day 15 and follow-up (Day 43)
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Day 15, A-NCS | 11 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Day 15, A-CS | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Follow-up (Day 43), A-CS | 2 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Follow-up (Day 43), A-NCS | 7 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Day 15, A-CS | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Follow-up (Day 43), A-NCS | 10 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Day 15, A-NCS | 11 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Follow-up (Day 43), A-CS | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Follow-up (Day 43), A-CS | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Day 15, A-CS | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Day 15, A-NCS | 6 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Follow-up (Day 43), A-NCS | 8 Participants |
Secondary
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.
Time frame: Day 29 and follow-up (Day 43)
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Glucose at Day 29 1 hour, 1+ OR 1/4 | 0 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Occult Blood at Day 29 1 hour, 1+ | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Day 29 1 hour, 2+ | 0 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Glucose at Follow-up, 3+ OR 1 gram/deciliter | 0 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Follow-up, 3+ | 0 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Day 29 1 hour, 1+ | 2 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Occult Blood at Follow-up, 1+ | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Occult Blood at Day 29 1 hour, 2+ | 0 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Follow-up, 1+ | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Follow-up, 3+ | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Occult Blood at Day 29 1 hour, 1+ | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Occult Blood at Day 29 1 hour, 2+ | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Occult Blood at Follow-up, 1+ | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Glucose at Day 29 1 hour, 1+ OR 1/4 | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Glucose at Follow-up, 3+ OR 1 gram/deciliter | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Day 29 1 hour, 1+ | 2 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Day 29 1 hour, 2+ | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Follow-up, 1+ | 2 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Glucose at Day 29 1 hour, 1+ OR 1/4 | 1 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Follow-up, 3+ | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Day 29 1 hour, 2+ | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Occult Blood at Follow-up, 1+ | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Occult Blood at Day 29 1 hour, 1+ | 2 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Follow-up, 1+ | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Glucose at Follow-up, 3+ OR 1 gram/deciliter | 1 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Occult Blood at Day 29 1 hour, 2+ | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Abnormal Urinalysis Data by Dipstick Analysis | Urine Protein at Day 29 1 hour, 1+ | 1 Participants |
Secondary
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.
Time frame: Day 29
Population: PD Parameter Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pazopanib 5 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Heme subretinal hemorrhage at Day 29 | 14 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Heme intraretinal hemorrhage at Day 29 | 7 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Subretinal fluid at Day 29 | 26 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Fibrosis at Day 29 | 2 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Atrophy at Day 29 | 6 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Pigment at Day 29 | 23 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Pigment at Day 29 | 20 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Heme subretinal hemorrhage at Day 29 | 14 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Fibrosis at Day 29 | 2 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Atrophy at Day 29 | 6 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Heme intraretinal hemorrhage at Day 29 | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Subretinal fluid at Day 29 | 22 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Heme intraretinal hemorrhage at Day 29 | 1 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Subretinal fluid at Day 29 | 11 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Pigment at Day 29 | 11 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Fibrosis at Day 29 | 1 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Heme subretinal hemorrhage at Day 29 | 7 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Change in Characteristics (Fibrosis, Atrophy, Blood) as Measured by Fundus Photography (FP) | Atrophy at Day 29 | 5 Participants |
Secondary
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.
Time frame: Day 29
Population: PD Parameter Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pazopanib 5 mg/mL TID | Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Pigment epithelial detachment at Day 29 | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Cystoid spaces at Day 29 | 9 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Subretinal fluid at Day 29 | 2 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Pigment epithelial detachment at Day 29 | 2 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Cystoid spaces at Day 29 | 10 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Subretinal fluid at Day 29 | 4 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Cystoid spaces at Day 29 | 5 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Subretinal fluid at Day 29 | 2 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Change in Retinal Morphology (Cystoid Spaces, Subretinal Fluid and Retinal Pigment Epithelial Detachment) as Determined by OCT | Pigment epithelial detachment at Day 29 | 1 Participants |
Secondary
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.
Time frame: Up to follow-up Day 43
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pazopanib 5 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Glucose high | 4 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Glucose low | 2 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Calcium low | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Potassium high | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Total bilirubin high | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Alkaline phosphatase high | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Lymphocytes low | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Total neutrophils low | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Calcium low | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Lymphocytes low | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Potassium high | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Total bilirubin high | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Alkaline phosphatase high | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Glucose high | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Glucose low | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Total neutrophils low | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Calcium low | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Glucose low | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Glucose high | 1 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Potassium high | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Lymphocytes low | 1 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Alkaline phosphatase high | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Total bilirubin high | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern | Total neutrophils low | 1 Participants |
Secondary
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.
Time frame: Upto follow-up (Day 43)
Population: Safety population comprised of all participants who received at least one dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pazopanib 5 mg/mL TID | Number of Participants With Complete Ophthalmic Examination Values of Potential Clinical Concern | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Complete Ophthalmic Examination Values of Potential Clinical Concern | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Complete Ophthalmic Examination Values of Potential Clinical Concern | 0 Participants |
Secondary
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
Time frame: Up to follow-up (Day 43)
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pazopanib 5 mg/mL TID | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Non-Ocular Adverse Events | 10 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Ocular Adverse Events, Fellow eye | 2 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Ocular Adverse Events, Study eye | 9 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Non-Ocular Serious Adverse Events | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Non-Ocular Serious Adverse Events | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Non-Ocular Adverse Events | 5 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Ocular Adverse Events, Study eye | 2 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Ocular Adverse Events, Fellow eye | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Non-Ocular Serious Adverse Events | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Ocular Adverse Events, Fellow eye | 1 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Ocular Adverse Events, Study eye | 3 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Ocular Adverse Events, Non-ocular Adverse Events, Serious Ocular Adverse Events and Serious Non-ocular Adverse Events | Non-Ocular Adverse Events | 2 Participants |
Secondary
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.
Time frame: Up to follow up (Day 46)
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pazopanib 5 mg/mL TID | Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Diastolic blood pressure | 0 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Systolic blood pressure | 1 Participants |
| Pazopanib 5 mg/mL TID | Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Heart rate | 0 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Diastolic blood pressure | 1 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Systolic blood pressure | 4 Participants |
| Pazopanib 2 mg/mL TID | Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Heart rate | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Systolic blood pressure | 1 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Heart rate | 0 Participants |
| Pazopanib 5 mg/mL Once Daily | Number of Participants With Vital Sign Data for Systolic Blood Pressure and Diastolic Blood Pressure and Heart Rate of Potential Clinical Concern | Diastolic blood pressure | 0 Participants |
Secondary
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.
Time frame: Day 15 and Day 22
Population: Pharmacokinetic population. Only those participants available at the specified time points were used for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pazopanib 5 mg/mL TID | Plasma Pharmacokinetic Parameter Area Under Concentration Time-curve From Time Zero to 6 Hours (AUC [0-6)] | Day 15 | 312.17998 nanograms per hour per milliliter | Geometric Coefficient of Variation 87.87 |
| Pazopanib 2 mg/mL TID | Plasma Pharmacokinetic Parameter Area Under Concentration Time-curve From Time Zero to 6 Hours (AUC [0-6)] | Day 15 | 124.57714 nanograms per hour per milliliter | Geometric Coefficient of Variation 77 |
| Pazopanib 2 mg/mL TID | Plasma Pharmacokinetic Parameter Area Under Concentration Time-curve From Time Zero to 6 Hours (AUC [0-6)] | Day 22 | 96.13500 nanograms per hour per milliliter | — |
Secondary
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.
Time frame: Day 15 and Day 22
Population: The pharmacokinetic population included all participants in the Safety Population who received at least one dose of active treatment and a PK sample was obtained and analyzed. Only those participants available at the specified time points were used for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pazopanib 5 mg/mL TID | Plasma Pharmacokinetic Parameter Maximum Observed Concentration (Cmax) | Day 15 | 56.104 nanograms per milliliter | Geometric Coefficient of Variation 85.38 |
| Pazopanib 2 mg/mL TID | Plasma Pharmacokinetic Parameter Maximum Observed Concentration (Cmax) | Day 15 | 21.142 nanograms per milliliter | Geometric Coefficient of Variation 75.53 |
| Pazopanib 2 mg/mL TID | Plasma Pharmacokinetic Parameter Maximum Observed Concentration (Cmax) | Day 22 | 17.680 nanograms per milliliter | — |
Secondary
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.
Time frame: Day 15 and Day 22
Population: Pharmacokinetic population. Only those participants available at the specified time points were used for analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pazopanib 5 mg/mL TID | Plasma Pharmacokinetic Parameter Time of Occurrence of Cmax (Tmax) | Day 15 | 3.000 hour |
| Pazopanib 2 mg/mL TID | Plasma Pharmacokinetic Parameter Time of Occurrence of Cmax (Tmax) | Day 15 | 2.970 hour |
| Pazopanib 2 mg/mL TID | Plasma Pharmacokinetic Parameter Time of Occurrence of Cmax (Tmax) | Day 29 | 3.000 hour |