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This is a two month study to allow continued treatment with pazopanib eye drops. Study may be extended to 5 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5 mg/ml TID | Experimental | eligible participants received 5 mg/ml Pazopanib eye drops three times daily (TID) |
|
| 2 mg/ml TID | Experimental | eligible participants received 2 mg/ml Pazopanib eye drops three times daily |
|
| 5 mg/ml QD | Experimental | eligible participants received 5 mg/ml Pazopanib eye drops once daily (QD) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pazopanib | Drug | 5 mg/ml TID, 2 mg/ml TID or 5 mg/ml QD |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline (Day 1) in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. SBP and DBP were recorded from Baseline up to 6 months. At screening and Baseline, if the single measured value of blood pressure was above 150 millimeters of mercury (mm Hg) systolic or 95 mm Hg diastolic, then blood pressure measurement could not be repeated. If, the SBP was <80 or >140 mm Hg and DBP was <40 or >90 mm Hg, then measurement of BP was repeated. Three consecutive blood pressure readings that were less than 150 mmHg systolic and 95 mmHg diastolic were taken with each measurement separated by at least 1 hour. | Baseline (Day 1) and approximately up to 6 months |
| Change From Baseline (Day 1) in Heart Rate Over Period | Heart rate was measured over 6 months. Baseline value was recorded on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Heart rate measurement were repeated in case it was in range < 50 beats per minute (bpm) or >110 bpm. | Baseline (Day 1) and approximately up to 6 months |
| Change From Baseline (Day 1) in Albumin and Hemoglobin Over Period | Albumin and hemoglobin values were recorded at Baseline, Month2, and till follow-up (Month 6). Baseline was recorded on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. | Baseline (Day 1), Month 2, 5 and approximately up to Month 6 |
| Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferases (ALT), and Aspartate Aminotransferases (AST) Over Period | ALP, ALT and AST values were measured over 5 months and till the follow-up period. Baseline value was recorded pre-dose Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. | Baseline (Day 1) and approximately up to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline (Screening Visit) in BCVA at Month 2 and 5 | Change from Baseline in BCVA is the value at indicated time point minus the Baseline value. BCVA at screening visit was used as statistical Baseline. Only data before post-dose intravitreal injection of Avastin/ Lucentis (IVT) has been presented. Arithmetic mean was presented as data values; however statistical analysis is based on means of observed case (OC) data. The screening was used as a Baseline visit that was within or at 14 days of Day 1. Screening visit BCVA values were used to perform statistical comparison at month 2 and 5. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Beverly Hills | California | 90211 | United States | ||
| GSK Investigational Site |
Randomized participants without progression of age-related macular degeneration (AMD) and/or requiring rescue therapy during the 28-day treatment period in study MD7108240 (NCT00612456) were included in this study. A total of 42 participants were randomized in the study.
This was an extension study to protocol MD7108240 (NCT00612456). It was a multi-center, double-masked, randomized, parallel-group dose-ranging study of repeat topical ocular doses of pazopanib from 25 June 2008 to 9 September 2009. The study was conducted in 14 centers in the United States, Italy, and Australia.
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| ID | Title | Description |
|---|---|---|
| FG000 | 5 mg/mL TID | Eligible participants received 5 milligram/milliliter (mg/mL) Pazopanib eye drops three times daily for a treatment period of five months. |
| FG001 | 2 mg/mL TID | Eligible participants received 2 mg/mL Pazopanib eye drops three times daily for a treatment period of five months. |
| FG002 | 5 mg/mL QD | Eligible participants received 5 mg/mL Pazopanib eye drops once daily for a treatment period of five months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 5 mg/mL TID | Eligible participants received 5 mg/mL Pazopanib eye drops three times daily for a treatment period of five months. |
| BG001 | 2 mg/mL TID | Eligible participants received 2 mg/mL Pazopanib eye drops three times daily for a treatment period of five months. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline (Day 1) in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. SBP and DBP were recorded from Baseline up to 6 months. At screening and Baseline, if the single measured value of blood pressure was above 150 millimeters of mercury (mm Hg) systolic or 95 mm Hg diastolic, then blood pressure measurement could not be repeated. If, the SBP was <80 or >140 mm Hg and DBP was <40 or >90 mm Hg, then measurement of BP was repeated. Three consecutive blood pressure readings that were less than 150 mmHg systolic and 95 mmHg diastolic were taken with each measurement separated by at least 1 hour. | Safety population included all participants who received at least one dose of the study drug. Only those participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | Millimeters of mercury (mmHg) | Baseline (Day 1) and approximately up to 6 months |
|
AEs and SAEs were collected approximately up to 6 months
Safety Population was used to collect AE and SAE data
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 5 mg/mL TID | Eligible participants received 5 mg/mL Pazopanib eye drops three times daily for a treatment period of five months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eye pain | Eye disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| D020256 | Choroidal Neovascularization |
| ID | Term |
|---|---|
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D015862 | Choroid Diseases |
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| ID | Term |
|---|---|
| C516667 | pazopanib |
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| Change From Baseline (Day 1) in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, and White Blood Cell Count Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. The above mentioned hematological parameters were recorded from Baseline up to 5 months. | Baseline (Day 1) and approximately up to 6 months |
| Change From Baseline (Day 1) in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Over here, the change is % Basophils at month x - % Basophils at Baseline. Baseline measurement was recorded at Day 1. Percentage change in the hematological parameter mentioned above was recorded from Baseline up to 5 months. | Baseline (Day 1) and approximately up to 6 months |
| Change From Baseline (Day 1) in Direct Bilirubin, Total Bilirubin, and Creatinine Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. Direct bilirubin, total bilirubin, and creatinine were recorded from Baseline up to 6 months | Baseline (Day 1) and approximately up to 6 months |
| Change From Baseline in Calcium, Chloride, Carbon di Oxide Equivalent Content, Glucose, Potassium, Sodium, and Urea Blood Urea Nitrogen (BUN) Over Period | Change from Baseline (Day 1) is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. Calcium, chloride, carbon di oxide equivalent content (CO2), glucose, potassium, sodium, and urea/blood urea nitrogen (BUN) was recorded from Baseline up to Follow-up. | Baseline (Day 1) and approximately up to 6 months |
| Change From Baseline (Day 1) in Mean Corpuscular Volume (MCV) Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. MCV was recorded from Baseline up to Follow-up. | Baseline (Day 1) and approximately up to 6 months |
| Change From Baseline (Day 1) in Intra-ocular Pressure Assessment Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. Intra-ocular pressure was recorded from Baseline up to Follow-up. | Baseline (Day 1) and approximately up to 6 months |
| Number of Participants With Blood Occult, Urine Glucose, Urine Ketones, and Urine Proteins by Dip Stick Analysis | In this dipstick test, the level of blood occult and glucose, ketones, protein in urine samples were recorded as negative, trace, 1+, 2+, and 3+ (the plus sign increases with a higher level of glucose, ketones, or proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). | Approximately up to 6 months (up to follow-up) |
| Number of Participants With Adverse Events (AEs)and Serious Adverse Events (SAEs) | Number of participants with ocular and non-ocular AEs and SAEs were separately recorded. An AE is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. An SAE is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. | Approximately up to 6 months |
| Number of Participants With Abnormal Visual Acuity of Potential Clinical Concern (PCI) | Visual acuity was measured over 5 months and also during follow-up period. Visual acuity was measured using standardized early treatment of diabetic retinopathy study (ETDRS) visual acuity charts. Visual acuity measurement was performed by an examiner that had been appropriately trained. Screening, Month 2 and Month 5 data were considered as Best Corrected Visual Acuity (BCVA) data. A loss of greater than or equal to 15 letters in BCVA from Baseline was considered of PCI. Data for number of participants who met the criteria for PCI have been presented. | Approximately up to 6 months |
| Number of Participants With Abnormal Pupil Examination of PCI | Pupil abnormalities were of different types. Meibomian gland dysfunction was measured as obvious inspissation (debris). Mild injection, no trichiasis (lid thickening), or two step worsening was analyzed. Afferent pupillary defect, motility examination, PERRL, confrontation visual field was measured as a new definite abnormality. Left and right both eyes were examined. | Up to follow-up (approximately 6 months) |
| Number of Participants With Abnormal Conjunctival Examination of PCI | A two step worsening in the conjunctival examination was considered a value of PCI. Participants were analyzed for conjunctival examination up to follow-up (6 months). | Up to follow-up (approximately 6 months) |
| Number of Participants With Abnormal Anterior Chamber Examination of PCI | A two step worsening in the anterior chamber examination was considered a value of PCI. The participants were examined for any anterior chamber abnormality. Fibrinous response and obvious aqueous haze were considered abnormalities related to anterior chamber examination. | Approximately up to 6 months |
| Number of Participants With Abnormal Corneal Examination of PCI | A two step change in any of the lens opacity categories was categorized as of PCI. Corneal epithelium was defined as abnormal when punctate keratopathy was measured as mild, moderate, severe; epithelial edema was measured as subtle epithelial haze, mild patchy microcystic changes, diffuse microcystic changes, and/or investigator determined abnormality. Stromal opacity/ edema was measured by investigator when stroma identifies opacity or edema. Corneal staining was measured as obvious (<=20) localized or diffuse punctate staining areas, severe localized or diffuse punctate staining. Participants were analyzed for any of the mentioned abnormality over 6 weeks (up to follow-up period). | Approximately up to 6 months |
| Number of Participants With Abnormal Lens Opacity of PCI Using Age Related Eye Disease Study (AREDS) Scale | A two step change in any of the lens opacity categories was considered a value of PCI. Aphakia (surgical removal of lens) or pseudophakia was noted if any. Stroma opacity or edema was measured by investigator when it was detected as edema or opacity in stroma. | Approximately up to 6 months |
| Number of Participants With Abnormal Tear Films of PCI | Tear film abnormalities were based on the clinical judgment of investigator. Tear film thickness was analyzed and it was reported whether the film was increased or decreased or was normal. Presence of debris or mucus was also reported. Other test were tear lake analysis and checking of discharge from eyes. | Approximately up to 6 months |
| Number of Participants With Any Grade 2 Plus Worsening of Meibomian Gland Function | Meibomian gland dysfunction was measured as obvious insipisation/debris, mild injection, no trichiasis or lid thickening; inspisation, debris, obvious injection, lid thickening, may have trsichiasis; or a two step worsening. Any 2+ worsening of Meibomian gland function was considered a value of PCI. | Approximately up to 6 months |
| Number of Participants With Abnormal (Dilated) Fundus Examination | Dilation of fundus was examined post dosing up to 6 months. Number of participants with abnormal change from Baseline indicating dilation of fundus of eye was reported. Change from Baseline was the value at indicated time point minus the Baseline value. The abnormalities were posterior vitreous separation, pale optic nerve, fluid in the posterior pole, drusen, thick arterio-venous changes, pigment changes, cystoids, macular edema, drying of posterior fluid or sub-retinal fluid, underlying central atrophy, and retinal pigment epithelial changes etc. Refraction measurement were determined at the screening and 2 month/5 month visits in order to determine BCVA. | Approximately up to 6 months |
| From Baseline (screening visit), Month 2, and Month 5 |
| Change From Baseline (Screening Visit) in Optical Coherence Tomography (OCT) Central Subfield Over 5 Months | The OCT effect is a pharmacodynamics (PD) measure of daily repeated dosing of Pazopanib. The anatomic effects of pazopanib treatment were limited to investigator determined assessment of OCT central subfield retinal thickness due to heterogeneity of participant population and the low likelihood of utility of central reading center determination. The OCT equipment used was approved by central OTC reading center. OCT scans were collected at indicated time points and were evaluated by Investigator. Thus, grading of further secondary objectives was not performed as per the study team. Change from Baseline is the value at indicated time point minus the Baseline value. The screening was used as a Baseline visit that was within or at 14 days of Day 1. Screening visit BCVA values were used to perform statistical comparison at month 2 and 5. | From Baseline (Screening visit) and up to 5 months |
| Change in Neo-vascular Size and Lesion Size Over Period | The analysis was planned to be performed up to 6 months; however, due to heterogeneity of the population and the low likelihood of the utility of the data, the anatomic effects of the pazopanib treatment in this treatment were limited to investigator determined assessment of OCT central subfield retinal thickness. Thus, the study team decided not to have DARC (central reading center) perform the grading for the secondary PD outcomes like lesion size and change with respect to time were not analyzed. Thus, data was not collected for this outcome measure. | Up to 6 weeks |
| Number of Participants With Lesion Types Over Period | Number of participants with type of lesion were reported as determined by Investigator. Occult and minimally classic were the two types of lesions reported. | Up to 6 months |
| Sacramento |
| California |
| 95841 |
| United States |
| GSK Investigational Site | Winter Haven | Florida | 33880 | United States |
| GSK Investigational Site | Indianapolis | Indiana | 46280 | United States |
| GSK Investigational Site | Boston | Massachusetts | 02111 | United States |
| GSK Investigational Site | Ann Arbor | Michigan | 48105 | United States |
| GSK Investigational Site | Grand Rapids | Michigan | 49525 | United States |
| GSK Investigational Site | Salt Lake City | Utah | 84132 | United States |
| GSK Investigational Site | Sydney | New South Wales | 2145 | Australia |
| GSK Investigational Site | Sydney | New South Wales | 2150 | Australia |
| GSK Investigational Site | Melbourne | Victoria | Australia |
| GSK Investigational Site | Perth | Western Australia | 6009 | Australia |
| GSK Investigational Site | Milan | Lombardy | 20132 | Italy |
| GSK Investigational Site | Milan | Lombardy | 20157 | Italy |
| GSK Investigational Site | Turin | Piedmont | 10122 | Italy |
| GSK Investigational Site | Florence | Tuscany | 50134 | Italy |
| GSK Investigational Site | Padova | Veneto | 35128 | Italy |
| Lost to Follow-up |
|
| Physician Decision |
|
| Withdrawal by Subject |
|
| BG002 | 5 mg/mL QD | Eligible participants received 5 mg/mL Pazopanib eye drops once daily for a treatment period of five months. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Safety Population | Count of Participants | Participants |
|
| Race (NIH/OMB) | Safety Population | Count of Participants | Participants |
|
| OG000 |
| 5 mg/mL TID |
Eligible participants received 5 mg/mL Pazopanib eye drops three times daily for a treatment period of five months and were followed-up for 7-14 days after the last dose of the study drug. |
| OG001 | 2 mg/mL TID | Eligible participants received 2 mg/mL Pazopanib eye drops three times daily for a treatment period of five months and were followed-up for 7-14 days after the last dose of the study drug. |
| OG002 | 5 mg/mL QD | Eligible participants received 5 mg/mL Pazopanib eye drops once daily for a treatment period of five months and were followed-up for 7-14 days after the last dose of the study drug. |
|
|
| Primary | Change From Baseline (Day 1) in Heart Rate Over Period | Heart rate was measured over 6 months. Baseline value was recorded on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Heart rate measurement were repeated in case it was in range < 50 beats per minute (bpm) or >110 bpm. | Safety population. Only the participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | bpm | Baseline (Day 1) and approximately up to 6 months |
|
|
|
| Primary | Change From Baseline (Day 1) in Albumin and Hemoglobin Over Period | Albumin and hemoglobin values were recorded at Baseline, Month2, and till follow-up (Month 6). Baseline was recorded on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. | Safety population. Only the participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | Grams per liter | Baseline (Day 1), Month 2, 5 and approximately up to Month 6 |
|
|
|
| Primary | Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferases (ALT), and Aspartate Aminotransferases (AST) Over Period | ALP, ALT and AST values were measured over 5 months and till the follow-up period. Baseline value was recorded pre-dose Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. | Safety population. Only the participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | International units per Liter (IU/L) | Baseline (Day 1) and approximately up to 6 months |
|
|
|
| Primary | Change From Baseline (Day 1) in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, and White Blood Cell Count Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. The above mentioned hematological parameters were recorded from Baseline up to 5 months. | Safety population. Only the participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | Giga per Liter (G/L) | Baseline (Day 1) and approximately up to 6 months |
|
|
|
| Primary | Change From Baseline (Day 1) in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Over here, the change is % Basophils at month x - % Basophils at Baseline. Baseline measurement was recorded at Day 1. Percentage change in the hematological parameter mentioned above was recorded from Baseline up to 5 months. | Safety population. Only the participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | Percentage of cells | Baseline (Day 1) and approximately up to 6 months |
|
|
|
| Primary | Change From Baseline (Day 1) in Direct Bilirubin, Total Bilirubin, and Creatinine Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. Direct bilirubin, total bilirubin, and creatinine were recorded from Baseline up to 6 months | Safety population. Only those participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | Micromoles per Liter (umol/L) | Baseline (Day 1) and approximately up to 6 months |
|
|
|
| Primary | Change From Baseline in Calcium, Chloride, Carbon di Oxide Equivalent Content, Glucose, Potassium, Sodium, and Urea Blood Urea Nitrogen (BUN) Over Period | Change from Baseline (Day 1) is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. Calcium, chloride, carbon di oxide equivalent content (CO2), glucose, potassium, sodium, and urea/blood urea nitrogen (BUN) was recorded from Baseline up to Follow-up. | Safety population. Only those participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | Millimoles per Liter (mmol/L) | Baseline (Day 1) and approximately up to 6 months |
|
|
|
| Primary | Change From Baseline (Day 1) in Mean Corpuscular Volume (MCV) Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. MCV was recorded from Baseline up to Follow-up. | Safety population. Only those participants available at the time of assessment were analyzed | Posted | Mean | Standard Deviation | Femtoliters | Baseline (Day 1) and approximately up to 6 months |
|
|
|
| Primary | Change From Baseline (Day 1) in Intra-ocular Pressure Assessment Over Period | Change from Baseline is the value at indicated time point minus the Baseline value. Baseline measurement was recorded at Day 1. Intra-ocular pressure was recorded from Baseline up to Follow-up. | Safety population. Only those participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline (Day 1) and approximately up to 6 months |
|
|
|
| Primary | Number of Participants With Blood Occult, Urine Glucose, Urine Ketones, and Urine Proteins by Dip Stick Analysis | In this dipstick test, the level of blood occult and glucose, ketones, protein in urine samples were recorded as negative, trace, 1+, 2+, and 3+ (the plus sign increases with a higher level of glucose, ketones, or proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). | Safety population. Only those participants available at the time of assessment were analyzed. | Posted | Count of Participants | Participants | Approximately up to 6 months (up to follow-up) |
|
|
|
| Primary | Number of Participants With Adverse Events (AEs)and Serious Adverse Events (SAEs) | Number of participants with ocular and non-ocular AEs and SAEs were separately recorded. An AE is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. An SAE is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. | Safety population. | Posted | Count of Participants | Participants | Approximately up to 6 months |
|
|
|
| Primary | Number of Participants With Abnormal Visual Acuity of Potential Clinical Concern (PCI) | Visual acuity was measured over 5 months and also during follow-up period. Visual acuity was measured using standardized early treatment of diabetic retinopathy study (ETDRS) visual acuity charts. Visual acuity measurement was performed by an examiner that had been appropriately trained. Screening, Month 2 and Month 5 data were considered as Best Corrected Visual Acuity (BCVA) data. A loss of greater than or equal to 15 letters in BCVA from Baseline was considered of PCI. Data for number of participants who met the criteria for PCI have been presented. | Safety population. Only those participants available at the time of assessment were analyzed. | Posted | Count of Participants | Participants | Approximately up to 6 months |
|
|
|
| Primary | Number of Participants With Abnormal Pupil Examination of PCI | Pupil abnormalities were of different types. Meibomian gland dysfunction was measured as obvious inspissation (debris). Mild injection, no trichiasis (lid thickening), or two step worsening was analyzed. Afferent pupillary defect, motility examination, PERRL, confrontation visual field was measured as a new definite abnormality. Left and right both eyes were examined. | Safety population. | Posted | Count of Participants | Participants | Up to follow-up (approximately 6 months) |
|
|
|
| Primary | Number of Participants With Abnormal Conjunctival Examination of PCI | A two step worsening in the conjunctival examination was considered a value of PCI. Participants were analyzed for conjunctival examination up to follow-up (6 months). | Safety population. | Posted | Count of Participants | Participants | Up to follow-up (approximately 6 months) |
|
|
|
| Primary | Number of Participants With Abnormal Anterior Chamber Examination of PCI | A two step worsening in the anterior chamber examination was considered a value of PCI. The participants were examined for any anterior chamber abnormality. Fibrinous response and obvious aqueous haze were considered abnormalities related to anterior chamber examination. | Safety population. | Posted | Count of Participants | Participants | Approximately up to 6 months |
|
|
|
| Primary | Number of Participants With Abnormal Corneal Examination of PCI | A two step change in any of the lens opacity categories was categorized as of PCI. Corneal epithelium was defined as abnormal when punctate keratopathy was measured as mild, moderate, severe; epithelial edema was measured as subtle epithelial haze, mild patchy microcystic changes, diffuse microcystic changes, and/or investigator determined abnormality. Stromal opacity/ edema was measured by investigator when stroma identifies opacity or edema. Corneal staining was measured as obvious (<=20) localized or diffuse punctate staining areas, severe localized or diffuse punctate staining. Participants were analyzed for any of the mentioned abnormality over 6 weeks (up to follow-up period). | Safety population | Posted | Count of Participants | Participants | Approximately up to 6 months |
|
|
|
| Primary | Number of Participants With Abnormal Lens Opacity of PCI Using Age Related Eye Disease Study (AREDS) Scale | A two step change in any of the lens opacity categories was considered a value of PCI. Aphakia (surgical removal of lens) or pseudophakia was noted if any. Stroma opacity or edema was measured by investigator when it was detected as edema or opacity in stroma. | Safety population | Posted | Count of Participants | Participants | Approximately up to 6 months |
|
|
|
| Primary | Number of Participants With Abnormal Tear Films of PCI | Tear film abnormalities were based on the clinical judgment of investigator. Tear film thickness was analyzed and it was reported whether the film was increased or decreased or was normal. Presence of debris or mucus was also reported. Other test were tear lake analysis and checking of discharge from eyes. | Safety population. | Posted | Count of Participants | Participants | Approximately up to 6 months |
|
|
|
| Primary | Number of Participants With Any Grade 2 Plus Worsening of Meibomian Gland Function | Meibomian gland dysfunction was measured as obvious insipisation/debris, mild injection, no trichiasis or lid thickening; inspisation, debris, obvious injection, lid thickening, may have trsichiasis; or a two step worsening. Any 2+ worsening of Meibomian gland function was considered a value of PCI. | Safety population. | Posted | Count of Participants | Participants | Approximately up to 6 months |
|
|
|
| Primary | Number of Participants With Abnormal (Dilated) Fundus Examination | Dilation of fundus was examined post dosing up to 6 months. Number of participants with abnormal change from Baseline indicating dilation of fundus of eye was reported. Change from Baseline was the value at indicated time point minus the Baseline value. The abnormalities were posterior vitreous separation, pale optic nerve, fluid in the posterior pole, drusen, thick arterio-venous changes, pigment changes, cystoids, macular edema, drying of posterior fluid or sub-retinal fluid, underlying central atrophy, and retinal pigment epithelial changes etc. Refraction measurement were determined at the screening and 2 month/5 month visits in order to determine BCVA. | Safety population. | Posted | Count of Participants | Participants | Approximately up to 6 months |
|
|
|
| Secondary | Change From Baseline (Screening Visit) in BCVA at Month 2 and 5 | Change from Baseline in BCVA is the value at indicated time point minus the Baseline value. BCVA at screening visit was used as statistical Baseline. Only data before post-dose intravitreal injection of Avastin/ Lucentis (IVT) has been presented. Arithmetic mean was presented as data values; however statistical analysis is based on means of observed case (OC) data. The screening was used as a Baseline visit that was within or at 14 days of Day 1. Screening visit BCVA values were used to perform statistical comparison at month 2 and 5. | Efficacy population included all participants in safety population who have classic choroidal neovascularization present as detected by fluorescein angiography in the previous screening visit. | Posted | Mean | Standard Deviation | Number of letters | From Baseline (screening visit), Month 2, and Month 5 |
|
|
|
|
| Secondary | Change From Baseline (Screening Visit) in Optical Coherence Tomography (OCT) Central Subfield Over 5 Months | The OCT effect is a pharmacodynamics (PD) measure of daily repeated dosing of Pazopanib. The anatomic effects of pazopanib treatment were limited to investigator determined assessment of OCT central subfield retinal thickness due to heterogeneity of participant population and the low likelihood of utility of central reading center determination. The OCT equipment used was approved by central OTC reading center. OCT scans were collected at indicated time points and were evaluated by Investigator. Thus, grading of further secondary objectives was not performed as per the study team. Change from Baseline is the value at indicated time point minus the Baseline value. The screening was used as a Baseline visit that was within or at 14 days of Day 1. Screening visit BCVA values were used to perform statistical comparison at month 2 and 5. | Pharmacodynamic subpopulation included participants that were analyzed for PD outcome measures. Only the participants available at the time of assessment were analyzed. | Posted | Mean | Standard Deviation | Microns | From Baseline (Screening visit) and up to 5 months |
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| Secondary | Change in Neo-vascular Size and Lesion Size Over Period | The analysis was planned to be performed up to 6 months; however, due to heterogeneity of the population and the low likelihood of the utility of the data, the anatomic effects of the pazopanib treatment in this treatment were limited to investigator determined assessment of OCT central subfield retinal thickness. Thus, the study team decided not to have DARC (central reading center) perform the grading for the secondary PD outcomes like lesion size and change with respect to time were not analyzed. Thus, data was not collected for this outcome measure. | PD population was planned for analysis of this outcome; however, Data was not collected for this outcome measure. | Posted | Up to 6 weeks |
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| Secondary | Number of Participants With Lesion Types Over Period | Number of participants with type of lesion were reported as determined by Investigator. Occult and minimally classic were the two types of lesions reported. | Safety population. | Posted | Count of Participants | Participants | Up to 6 months |
|
|
|
| 0 |
| 19 |
| 2 |
| 19 |
| 15 |
| 19 |
| EG001 | 2 mg/mL TID | Eligible participants received 2 mg/mL Pazopanib eye drops three times daily for a treatment period of five months. | 0 | 15 | 1 | 15 | 9 | 15 |
| EG002 | 5 mg/mL QD | Eligible participants received 5 mg/mL Pazopanib eye drops once daily for a treatment period of five months. | 0 | 8 | 0 | 8 | 3 | 8 |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Cataract | Eye disorders | MedDRA | Systematic Assessment |
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| Keratoconjunctivitis sicca | Eye disorders | MedDRA | Systematic Assessment |
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| Macular degeneration | Eye disorders | MedDRA | Systematic Assessment |
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| Retinal disorder | Eye disorders | MedDRA | Systematic Assessment |
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| Retinal haemorrhage | Eye disorders | MedDRA | Systematic Assessment |
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| Blepharitis | Eye disorders | MedDRA | Systematic Assessment |
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| Cataract | Eye disorders | MedDRA | Systematic Assessment |
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| Cataract nuclear | Eye disorders | MedDRA | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA | Systematic Assessment |
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| Optic disc haemorrhage | Eye disorders | MedDRA | Systematic Assessment |
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| Photopsia | Eye disorders | MedDRA | Systematic Assessment |
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| Posterior capsule opacification | Eye disorders | MedDRA | Systematic Assessment |
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| Visual impairment | Eye disorders | MedDRA | Systematic Assessment |
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| Vitreous detachment | Eye disorders | MedDRA | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
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| Localised infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Ankle fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Wrist fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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| Seasonal allergy | Immune system disorders | MedDRA | Systematic Assessment |
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| Blood cholesterol increased | Investigations | MedDRA | Systematic Assessment |
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| Blood glucose increased | Investigations | MedDRA | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA | Systematic Assessment |
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| Hypothyroidism | Endocrine disorders | MedDRA | Systematic Assessment |
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| Sensation of foreign body | General disorders | MedDRA | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D014603 |
| Uveal Diseases |
| D009389 | Neovascularization, Pathologic |
| D008679 | Metaplasia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Month 2 |
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| Month 3 |
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| Month 4 |
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| Month 5 |
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| Follow-up |
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| Albumin, Month 5 |
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| Albumin, Follow-up |
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| Hemoglobin, Month 2 |
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| Hemoglobin, Month 5 |
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| Hemoglobin, Follow-up |
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| ALP, Month 2 |
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| ALP, Month 3 |
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| ALP, Month 4 |
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| ALP, Month 5 |
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| ALP, Follow-up |
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| ALT, Month 1 |
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| ALT, Month 2 |
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| ALT, Month 3 |
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| ALT, Month 4 |
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| ALT, Month 5 |
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| ALT, Follow-up |
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| AST, Month 1 |
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| AST, Month 2 |
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| AST, Month 3 |
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| AST, Month 4 |
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| AST, Month 5 |
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| AST, Follow-up |
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| Basophils, Month 5 |
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| Bsophils, Follow-up |
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| Eosinophils, Month 2 |
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| Eosinophils, Month 5 |
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| Eosinophils,Follow-up |
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| Lymphocytes, Month 2 |
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| Lymphocytes, Month 5 |
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| Lymphocytes, Follow-up |
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| Monocytes, Month 2 |
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| Monocytes, Month 5 |
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| Monocytes, Follow-up |
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| Platelets, Month 2 |
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| Platelets, Month 5 |
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| Platelets, Follow-up |
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| White blood cells, Month 2 |
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| White blood cells, Month 5 |
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| White blood cells, Follow-up |
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| % Basophils, Month 5 |
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| % Basophils, Follow-up |
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| % Eosinophils, Month 2 |
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| % Eosinophils, Month 5 |
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| % Eosinophils,Follow-up |
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| % lymphocytes, Month 2 |
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| % lymphocytes, Month 5 |
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| % lymphocytes, Follow-up |
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| % monocytes, Month 2 |
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| % monocytes, Month 5 |
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| % monocytes, Follow-up |
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| %Total neutrophils, Month 2 |
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| %Total neutrophils, Month 5 |
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| %Total neutrophils, Follow-up |
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| Direct bilirubin, Month 2 |
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| Direct bilirubin, Month 3 |
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| Direct bilirubin, Month 4 |
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| Direct bilirubin, Month 5 |
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| Direct bilirubin, Follow-up |
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| Total bilirubin, Month 1 |
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| Total bilirubin, Month 2 |
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| Total bilirubin, Month 3 |
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| Total bilirubin, Month 4 |
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| Total bilirubin, Month 5 |
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| Total bilirubin, Follow-up |
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| Creatinine, Month 2 |
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| Creatinine, Month 5 |
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| Creatinine, Follow-up |
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| Calcium, Month 5 |
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| Calcium, Follow-up |
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| Chloride, Month 2 |
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| Chloride, Month 5 |
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| Chloride, Follow-up |
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| CO2, Month 2 |
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| CO2, Month 5 |
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| CO2, Follow-up |
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| Glucose, Month 2 |
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| Glucose, Month 5 |
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| Glucose, Follow-up |
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| Potassium, Month 2 |
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| Potassium, Month 5 |
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| Potassium, Follow-up |
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| Sodium, Month 2 |
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| Sodium, Month 5 |
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| Sodium, Follow-up |
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| Urea/BUN, Month 2 |
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| Urea/BUN, Month 5 |
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| Urea/BUN, Follow-up |
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| Month 5 |
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| Follow-up |
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| Month 2 |
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| Month 3 |
|
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| Month 4 |
|
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| Month 5 |
|
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| Month Follow-up |
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| Urine blood occult, Month 2, traces |
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| Urine blood occult, Month 5, traces |
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| Urine blood occult, Follow-up, traces |
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| Urine glucose, Month 5, traces |
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| Urine glucose, Follow-up, 1+ OR 1/4/G/DL (5%) |
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| Urine ketones, Month 2, traces |
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| Urine ketones, Follow-up, traces |
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| Urine protein, Month 2, 1+ |
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| Urine protein, Month 2, traces |
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| Urine protein, Month 5, 1+ |
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| Urine protein, Follow-up, 1+ |
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| Urine protein, Follow-up, traces |
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| Title | Measurements |
|---|---|
|
| Any AE, ocular |
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| Any SAE, ocular |
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| IVT Treatment naive, Month 5 |
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| Previously treated with IVT, Month 2 |
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| Previously treated with IVT, Month 5 |
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Month 5 versus screening visit
| ANCOVA |
Analysis of covariance (ANCOVA) model was used to perform statistical analysis based on treatment, visit, fixed effect terms etc. |
| Mean Difference (Net) |
| -3.80 |
| Standard Error of the Mean |
| 1.659 |
| 2-Sided |
| 95 |
| -7.13 |
| -0.46 |
| Superiority |
| Month 2 versus screening visit | ANCOVA | Analysis of covariance (ANCOVA) model was used to perform statistical analysis based on treatment, visit, fixed effect terms etc. | Mean Difference (Net) | -4.15 | Standard Error of the Mean | 1.672 | 2-Sided | 95 | -7.52 | -0.78 | Superiority |
| Month 5 versus screening visit | ANCOVA | Analysis of covariance (ANCOVA) model was used to perform statistical analysis based on treatment, visit, fixed effect terms etc. | Mean Difference (Net) | -4.03 | Standard Error of the Mean | 1.740 | 2-Sided | 95 | -7.53 | 0.53 | Superiority |
| Treatment naive, Month 2 |
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| Treatment naive, Month 3 |
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| Treatment naive, Month 4 |
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| Treatment naive, Month 5 |
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| Previously treated, Month 1 |
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| Previously treated, Month 2 |
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| Previously treated, Month 3 |
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| Previously treated, Month 4 |
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| Previously treated, Month 5 |
|
|
Month 2 versus Screening visit |
| ANCOVA |
ANCOVA model was used to perform statistical analysis based on treatment, visit, fixed effect terms, Baseline OCT central subfield as covariate, and participant within treatment as a random effect term. |
| Mean Difference (Net) |
| -1.21 |
| Standard Error of the Mean |
| 17.177 |
| 2-Sided |
| 95 |
| -35.73 |
| 33.31 |
| Superiority |
| Month 3 versus Screening visit | ANCOVA | ANCOVA model was used to perform statistical analysis based on treatment, visit, fixed effect terms, Baseline OCT central subfield as covariate, and participant within treatment as a random effect term. | Mean Difference (Net) | -5.11 | Standard Error of the Mean | 17.958 | 2-Sided | 95 | -41.08 | 30.86 | Superiority |
| Month 4 versus Screening visit | ANCOVA | ANCOVA model was used to perform statistical analysis based on treatment, visit, fixed effect terms, Baseline OCT central subfield as covariate, and participant within treatment as a random effect term. | Mean Difference (Net) | -9.92 | Standard Error of the Mean | 18.996 | 2-Sided | 95 | -47.83 | 28.00 | Superiority |
| Month 5 versus Screening visit | ANCOVA | ANCOVA model was used to perform statistical analysis based on treatment, visit, fixed effect terms, Baseline OCT central subfield as covariate, and participant within treatment as a random effect term. | Mean Difference (Net) | 2.42 | Standard Error of the Mean | 18.996 | 2-Sided | 95 | -35.50 | 40.33 | Superiority |
| Month 1 versus Screening visit | ANCOVA | ANCOVA model was used to perform statistical analysis based on treatment, visit, fixed effect terms, Baseline OCT central subfield as covariate, and participant within treatment as a random effect term. | Mean Difference (Net) | 9.05 | Standard Error of the Mean | 20.931 | 2-Sided | 95 | -33.09 | 51.20 | Superiority |
| Month 2 versus Screening visit | ANCOVA | ANCOVA model was used to perform statistical analysis based on treatment, visit, fixed effect terms, Baseline OCT central subfield as covariate, and participant within treatment as a random effect term. | Mean Difference (Net) | -1.24 | Standard Error of the Mean | 21.290 | 2-Sided | 95 | -44.05 | 41.57 | Superiority |
| Month 3 versus Screening visit | ANCOVA | ANCOVA model was used to perform statistical analysis based on treatment, visit, fixed effect terms, Baseline OCT central subfield as covariate, and participant within treatment as a random effect term. | Mean Difference (Net) | 15.39 | Standard Error of the Mean | 21.757 | 2-Sided | 95 | -28.28 | 59.06 | Superiority |
| Month 4 versus Screening visit | ANCOVA | ANCOVA model was used to perform statistical analysis based on treatment, visit, fixed effect terms, Baseline OCT central subfield as covariate, and participant within treatment as a random effect term. | Mean Difference (Net) | -16.82 | Standard Error of the Mean | 22.183 | 2-Sided | 95 | -61.28 | 27.63 | Superiority |
| Month 5 versus Screening visit | ANCOVA | ANCOVA model was used to perform statistical analysis based on treatment, visit, fixed effect terms, Baseline OCT central subfield as covariate, and participant within treatment as a random effect term. | Mean Difference (Net) | -2.16 | Standard Error of the Mean | 21.757 | 2-Sided | 95 | -45.83 | 41.51 | Superiority |
| Title | Measurements |
|---|---|
|