12 Week Patient Study in Neovascular Age-related Macular Degeneration (AMD)

• ClinicalTrials.gov Identifier: NCT01362348
• Recruitment Status: Terminated
• First Posted: May 30, 2011
• Results First Posted: August 21, 2017
• Last Update Posted: September 21, 2017
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Macular Degeneration
• Intervention: Drug: pazopanib eye drops
• Enrollment: 19

Participant Flow

Recruitment Details	This study was conducted at 10 sites in the United States, Germany and France from 7 July 2011 was early terminated on 22 Mar 2012 and completed on 16 April 2012. The study was terminated due to lack of efficacy.
Pre-assignment Details

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description	Eligible participants instilled a single drop (approximately 40 micro liters ) of the pazopanib ophthalmic solution 10 milligram per millimeter (mg/mL) via topical ocular route to the study eye at approximate 5 hour intervals four times a day (QID) during the non-sleep period for a duration of 12 weeks.
Period Title: Overall Study
Started	19
Completed	5
Not Completed	14
Reason Not Completed
Protocol-defined stopping criteria	9
Study closed/terminated	5

Baseline Characteristics

Arm/Group Title		Pazopanib 10 mg/mL QID
Arm/Group Description		Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Baseline Participants		19
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	19 participants
		76.3 (6.65)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Female	14 73.7%
	Male	5 26.3%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	19 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Central Retinal Lesion Thickness (CRT) as Measured by Optical Coherence Tomography (OCT) at Day 29
Description	CRT was the distance between the inner limiting membrane of the retina and the inner border of the retinal pigment epithelium/choriocapillaris band, inclusive of sub retinal fluid, measured in the central 1 millimeter (mm) of the Cube scan. OCT assessments were performed using SPECTRALIS spectral domain OCT. Images were evaluated by investigator for safety monitoring, and by a central reading center for eligibility determination and pharmacodynamics (PD) effects. Observed case (OC) data set was used for analysis in this analysis dataset, a missing assessment at any scheduled time point was considered unevaluable, was not imputed and was not included in data analysis. 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 (Week 0) and Day 29

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) Population comprised of any participant who received at least one dose of study medication. Only those participants with data available at the indicated time point were analyzed. OC dataset was used for analysis.

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description:	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: Microns
	37.91 (89.692)

2. Primary Outcome

Title	Change From Baseline in Best Correct Visual Acuity (BCVA) as Measured by the Number of Letters Determined by Electronic Early Treatment Diabetic Retinopathy [ETDRS] Study Visual Acuity (EVA) at Day 29
Description	BCVA was measured in the study eye using the EVA chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the participant. A decrease in the BCVA score indicates a worsening of vision while higher scores indicates improvement of VA. 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

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the indicated time point were analyzed. OC dataset was used for analysis.

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description:	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: Count of letters
	0.07 (9.973)

3. Secondary Outcome

Title	Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time
Description	CRLT was the manual measurement of the distance between the inner limiting membrane of the retina and the inner border of the choriocapillaris, inclusive of subretinal or sub-retinal pigment epithelium fluid collections and of the thickness of any observable choroidal neovascular membrane or scar tissue, evaluated in the central 1 mm of the Cube scan. OCT assessments were performed using SPECTRALIS spectral domain OCT. 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 (Week -3 to -1) Up to Follow-up (Day 102)

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed. OC dataset was used for analysis.

Arm/Group Title		Pazopanib 10 mg/mL QID
Arm/Group Description:		Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: Microns
CRLT at Week 1	Number Analyzed	19 participants
		-3.97 (93.420)
CRLT at Week 2	Number Analyzed	19 participants
		-6.39 (93.420)
CRLT at Week 3	Number Analyzed	14 participants
		15.15 (86.646)
CRLT at Week 4	Number Analyzed	13 participants
		31.72 (88.289)
CRLT at Week 6	Number Analyzed	10 participants
		51.22 (84.679)
CRLT at Week 8	Number Analyzed	8 participants
		15.48 (82.304)
CRLT at Week 12	Number Analyzed	6 participants
		-1.57 (75.216)
CRLT at Follow-up	Number Analyzed	11 participants
		-8.42 (91.346)

4. Secondary Outcome

Title	Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
Description	OCT was used for the determination of retinal morphology changes in the study eye which included assessments of SR fluid (an exudate between the retina and choroid from various sources including the vitreous cavity, subarachnoid space, or abnormal vessels) and PED (retinal pigment epithelium separates from the underlying Bruch's membrane due to the presence of blood, serous exudate, drusen, or a neovascular membrane). 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 (Week -3 to -1) Up to Follow-up (Day 102)

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed. OC dataset was used for analysis.

Arm/Group Title		Pazopanib 10 mg/mL QID
Arm/Group Description:		Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: Microns
SR fluid thickness at Week 1	Number Analyzed	17 participants
		-34.79 (70.781)
SR fluid thickness at Week 2	Number Analyzed	18 participants
		-29.32 (71.654)
SR fluid thickness at Week 3	Number Analyzed	13 participants
		-0.22 (67.074)
SR fluid thickness at Week 4	Number Analyzed	12 participants
		5.69 (67.938)
SR fluid thickness at Week 6	Number Analyzed	10 participants
		28.05 (67.192)
SR fluid thickness at Week 8	Number Analyzed	7 participants
		35.25 (64.689)
SR fluid thickness at Week 12	Number Analyzed	4 participants
		1.72 (57.734)
SR fluid thickness at Follow-up	Number Analyzed	8 participants
		8.43 (70.329)
PED thickness at Week 1	Number Analyzed	12 participants
		4.01 (56.669)
PED thickness at Week 2	Number Analyzed	12 participants
		4.47 (56.669)
PED thickness at Week 3	Number Analyzed	9 participants
		14.00 (53.040)
PED thickness at Week 4	Number Analyzed	9 participants
		7.16 (54.843)
PED thickness at Week 6	Number Analyzed	5 participants
		37.93 (49.035)
PED thickness at Week 8	Number Analyzed	3 participants
		36.57 (46.786)
PED thickness at Week 12	Number Analyzed	3 participants
		-32.68 (46.509)
PED thickness at Follow-up	Number Analyzed	7 participants
		-19.04 (56.214)

5. Secondary Outcome

Title	Change From Baseline in BCVA Over Time
Description	BCVA was measured in the study eye using the EVA chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the participant. A decrease in the BCVA score indicates a worsening of vision while higher scores indicates improvement of VA. 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 (Week -3 to -1) Up to Follow-up (Day 102)

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed. OC dataset was used for analysis.

Arm/Group Title		Pazopanib 10 mg/mL QID
Arm/Group Description:		Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: Letters
Week 1	Number Analyzed	19 participants
		0.26 (11.015)
Week 2	Number Analyzed	19 participants
		0.26 (11.015)
Week 3	Number Analyzed	14 participants
		-1.47 (9.927)
Week 4	Number Analyzed	13 participants
		0.07 (9.973)
Week 6	Number Analyzed	10 participants
		1.76 (9.345)
Week 8	Number Analyzed	8 participants
		0.63 (8.912)
Week 12	Number Analyzed	6 participants
		-0.85 (8.069)
Follow-up	Number Analyzed	11 participants
		-5.49 (10.388)

6. Secondary Outcome

Title	Change From Baseline in the Area of Choroidal Neovascular (CNV) Size and CNV Total Lesion Complex Size as Measured by Fluorescein Angiography (FA) at Day 29
Description	CNV was the measurement of the combined classic and occult neovascular lesion including areas of classic neovascularization, late staining of undetermined origin and fibrovascular PED. CNV total lesion complex size was the measurement of the entire lesion including classic and occult neovascular components as well as contagious blood and/or blocked fluorescence and/or serous PED. FA uses fundus photography (FP) to capture images of injected dye circulating throughout the retinal blood vessels to assess leaking, swelling/circulation problems caused by various eye diseases like diabetic retinopathy and wet macular degeneration. A fluorescein angiogram was obtained at Day 29. Images were evaluated by investigator for eligibility and by a central reading center for determination of PD effect. 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

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the indicated time point were analyzed. OC dataset was used for analysis.

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description:	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed	13
Mean (Standard Deviation); Unit of Measure: millimeter square
CNV Size at Week 4	1.38 (2.902)
CNV total lesion complex size at Week 4	1.37 (2.892)

7. Secondary Outcome

Title	Number of Participants With Change in Charactertsics (Atrophy, Pigment, SR Hemorrhage, IR Hemorrhage, SR Fluid and Fibrosis) as Measured by FP
Description	Fundus photography involves capturing of images of the center of the very back inner wall of the eye - the retina, optic nerve, macula and main retinal blood vessels. The parameters assessment were heme SR hemorrhage (absence or presence at the location), heme IR hemorrhage (absence or presence at the location), SR 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

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the indicated time point were analyzed. OC dataset was used for analysis.

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description:	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed	13
Measure Type: Count of Participants; Unit of Measure: Participants
Atrophy at Week 4	0 0.0%
Pigment at Week 4	12 92.3%
Heme (SR) at Week 4	10 76.9%
Heme (IR) at Week 4	1 7.7%
SR fluid at Week 4	13 100.0%
Fibrosis at Week 4	1 7.7%

8. Secondary Outcome

Title	Number of Participants Who Received Rescue Medication
Description	At any time during the study, including the follow-up period, rescue treatment (standard of care) was given based on the clinical judgment of the investigator. Rescue treatment was to be strongly considered for participants whose center subfield thickness had increased by >50 microns from the lowest value on study or whose BCVA decreased by more than 5 letters compared to baseline and who also had persistent fluid by OCT. Data has been reported for the number of participants with their percentages who required any rescue medication administration until follow-up.
Time Frame	Up to follow-up (Day 102)

Outcome Measure Data

Analysis Population Description

Safety Population comprised of any participant who received at least one dose of study medication.

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description:	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
	9 47.4%

9. Secondary Outcome

Title	Number of Participants With Ocular Adverse Events (AEs), Non-ocular AEs, Serious Ocular AEs and Serious Non-ocular AEs
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Time Frame	Until Follow-up (Day 102)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description:	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
Any Ocular AE	8 42.1%
Any Ocular SAE	0 0.0%
Any Non-Ocular AE	9 47.4%
Any Non-Ocular SAE	0 0.0%

10. Secondary Outcome

Title	Number of Participants With Values of Potential Clinical Concern for Ocular Assessments on General Ophthalmic Examination
Description	A complete eye examination was performed to include the following: Examination of eyelids and lashes (including meibomian glands), Pupil, motility and confrontation visual field examination, Slit lamp evaluation of anterior ocular structures (including conjunctiva, tear film, cornea with fluorescein staining, anterior chamber, iris, lens, and anterior vitreous), Intraocular pressure (IOP) measurement and Dilated Fundus Examination (Indirect ophthalmoscopy and slit lamp biomicroscopy). Data has been presented in a consolidated format for the total number of participants with values of potential clinical concern for complete ophthalmic examinations until Day 102.
Time Frame	Up to Follow-up (Day 102)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description:	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

11. Secondary Outcome

Title	Number of Participants With Vital Sign Data of Potential Clinical Concern
Description	Vital sign assessments included systolic blood pressure, diastolic blood pressure and heart rate. The potential clinical concern range for systolic blood pressure was <85 and >160 millimeters of mercury, diastolic blood pressure <45 and > 100 millimeters of mercury, heart rate <40 and >110 beats per minute. Data has been presented in a consolidated format for the total number of participants with values of potential clinical concern for systolic blood pressure, diastolic blood pressure and heart rate until Day 102.
Time Frame	Up to Follow-up (Day 102)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description:	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
Systolic blood pressure	2 10.5%
Diastolic blood pressure	0 0.0%
Heart rate	0 0.0%

12. Secondary Outcome

Title	Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern
Description	Clinical chemistry parameters included albumin, alkaline phosphatase, alanine amino transferase, aspartate amino transferase, direct bilirubin, total bilirubin, calcium, chloride, carbon dioxide, creatinine, thyroxine (T3 free), gamma glutamyl transferase, glucose, potassium, sodium, total protein, total T3, urea, uric acid while hematology included basophils, eosinophils, hemoglobin, hematocrit, lymphocytes, mean corpuscle hemoglobin concentration, mean corpuscle hemoglobin, mean corpuscle volume, monocytes, segmented neutrophils, total neutrophils, platelet count, red blood cell count, reticulocytes and white blood cell count. The potential clinical concern ranges were as follows: glucose-low <3 and high >9 millimoles per liter (mmol/L), carbon dioxide-low <18 and high >34 mmol/L, lymphocyte-low <0.8 giga per liter (G/L) and platelet count was <100 and high >550 G/L. Data has been presented for the number of participants with values high and low of potential clinical concern.
Time Frame	Up to Follow-up (Day 102)

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description:	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
Glucose high	1 5.3%
Carbon dioxide low	2 10.5%
Lymphocyte low	1 5.3%
Platelet count low	1 5.3%

13. Secondary Outcome

Title	Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Description	Urinalysis measurements included assessments for red blood cells and white blood cells via microscopic examination while assessments for urine protein by standard dipstick analysis. Data has been presented for the number of participants with abnormal urinalysis results.
Time Frame	Up to Follow-up (Day 102)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed,

Arm/Group Title		Pazopanib 10 mg/mL QID
Arm/Group Description:		Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed		19
Measure Type: Count of Participants; Unit of Measure: Participants
Red blood cells 3-5 at Week 2	Number Analyzed	1 participants
		1 100.0%
Red blood cells 0-1 at Week 4	Number Analyzed	3 participants
		1 33.3%
Red blood cells 1-3 at Week 4	Number Analyzed	3 participants
		1 33.3%
Red blood cells 25-50 at Week 4	Number Analyzed	3 participants
		1 33.3%
Red blood cells 1-3 at Follow-up	Number Analyzed	5 participants
		1 20.0%
Red blood cells 5-10 at Follow-up	Number Analyzed	5 participants
		2 40.0%
White blood cells 3-5 at Week 2	Number Analyzed	1 participants
		1 100.0%
White blood cells 1-3 at Week 4	Number Analyzed	3 participants
		1 33.3%
White blood cells 5-10 at Week 4	Number Analyzed	3 participants
		1 33.3%
White blood cells 10-15 at Follow-up	Number Analyzed	5 participants
		1 20.0%
White blood cells 50-100 at Follow-up	Number Analyzed	5 participants
		1 20.0%
Urine protein 2+ at Week 4	Number Analyzed	13 participants
		1 7.7%
Urine protein 1+ at Week 12	Number Analyzed	6 participants
		1 16.7%
Urine protein 2+ at Week 12	Number Analyzed	6 participants
		1 16.7%
Urine protein 1+ at Follow-up	Number Analyzed	17 participants
		1 5.9%
Urine protein 3+ at Follow-up	Number Analyzed	17 participants
		1 5.9%

14. Secondary Outcome

Title	Summary of Plasma Pazonib Concentration
Description	Throughout the study, 1 to 4 blood samples (2 mL) were collected from each participants for the analysis of plasma pazopanib concentrations between 0.55 to 10.83 hours post-dose on Weeks 2, 3, 4, 6 (unplanned), 8 (unplanned) and 12. The concentrations from the three blood samples per participant were averaged and then the values were averaged through all the participants. Blood samples were collected without restriction for the time interval between blood draw and the last dose of pazopanib eye drops.
Time Frame	Up to Week 12

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population was defined as participants in the ITT Population for whom a pharmacokinetic sample was obtained and analyzed. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Pazopanib 10 mg/mL QID
Arm/Group Description:		Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: nanograms per milliliter
Week 2	Number Analyzed	19 participants
		279.0 (171.66)
Week 3	Number Analyzed	7 participants
		323.9 (216.77)
Week 4	Number Analyzed	14 participants
		360.5 (215.80)
Week 6	Number Analyzed	1 participants
		498.0 [1] (NA)
Week 8	Number Analyzed	1 participants
		150.0 [1] (NA)
Week 12	Number Analyzed	6 participants
		255.3 (170.06)

[1]

Standard could was not computed as a single participant was analyzed.

Adverse Events

Time Frame	Up to Follow-up (Day 102)
Adverse Event Reporting Description	Safety population was used for analysis.
Arm/Group Title	Pazopanib 10 mg/mL QID
Arm/Group Description	Eligible participants instilled a single drop (approximately 40 microliters ) of the pazopanib ophthalmic solution 10 mg/mL via topical ocular route to the study eye at approximate 5 hour intervals QID during the non-sleep period for a duration of 12 weeks.
All-Cause Mortality
	Pazopanib 10 mg/mL QID
	Affected / at Risk (%)
Total	0/19 (0.00%)
Serious Adverse Events
	Pazopanib 10 mg/mL QID
	Affected / at Risk (%)
Total	0/19 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pazopanib 10 mg/mL QID
	Affected / at Risk (%)
Total	17/19 (89.47%)
Eye disorders
Age-related macular degeneration † 1	2/19 (10.53%)
Macular oedema † 1	1/19 (5.26%)
Ocular Hypertension † 1	1/19 (5.26%)
Retinal haemorrhage † 1	1/19 (5.26%)
Vitreous floaters † 1	1/19 (5.26%)
Gastrointestinal disorders
Nausea † 1	1/19 (5.26%)
Oesophageal obstruction † 1	1/19 (5.26%)
General disorders
Instillation site pain † 1	3/19 (15.79%)
Infections and infestations
Tooth infection † 1	1/19 (5.26%)
Urinary tract infection † 1	1/19 (5.26%)
Injury, poisoning and procedural complications
Skeletal injury † 1	1/19 (5.26%)
Investigations
Platelet count decreased † 1	1/19 (5.26%)
Protein urine present † 1	1/19 (5.26%)
Red blood cells urine positive † 1	1/19 (5.26%)
Urine protein/creatinine ratio increased † 1	1/19 (5.26%)
Musculoskeletal and connective tissue disorders
Arthritis † 1	1/19 (5.26%)
Tendonitis † 1	1/19 (5.26%)
Torticollis † 1	1/19 (5.26%)
Psychiatric disorders
Depression † 1	1/19 (5.26%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/19 (5.26%)
Dyshponia † 1	1/19 (5.26%)
Vascular disorders
Hypertension † 1	1/19 (5.26%)
1 Term from vocabulary, MedDRA; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: GSK Response Center
• Organization: GlaxoSmithKline
• Phone: 866-435-7343

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Singh R, Wurzelmann JI, Ye L, Henderson L, Hossain M, Trivedi T, Kelly DS. Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects with neovascular age-related macular degeneration. Retina. 2014 Sep;34(9):1787-95. doi: 10.1097/IAE.0000000000000179.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01362348
• Other Study ID Numbers: 114987
• First Submitted: May 19, 2011
• First Posted: May 30, 2011
• Results First Submitted: July 18, 2017
• Results First Posted: August 21, 2017
• Last Update Posted: September 21, 2017