Trial Outcomes & Findings for 12 Week Patient Study in Neovascular Age-related Macular Degeneration (AMD) (NCT NCT01362348)
NCT ID: NCT01362348
Last Updated: 2017-09-21
Results Overview
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.
TERMINATED
PHASE2
19 participants
Baseline (Week 0) and Day 29
2017-09-21
Participant Flow
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.
Participant milestones
| Measure |
Pazopanib 10 mg/mL QID
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.
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|---|---|
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Overall Study
STARTED
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19
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Overall Study
COMPLETED
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5
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Overall Study
NOT COMPLETED
|
14
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Reasons for withdrawal
| Measure |
Pazopanib 10 mg/mL QID
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.
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|---|---|
|
Overall Study
Protocol-defined stopping criteria
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9
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Overall Study
Study closed/terminated
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5
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Baseline Characteristics
12 Week Patient Study in Neovascular Age-related Macular Degeneration (AMD)
Baseline characteristics by cohort
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
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|---|---|
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Age, Continuous
|
76.3 Years
STANDARD_DEVIATION 6.65 • n=5 Participants
|
|
Sex: Female, Male
Female
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14 Participants
n=5 Participants
|
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Sex: Female, Male
Male
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5 Participants
n=5 Participants
|
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Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week 0) and Day 29Population: 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.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=13 Participants
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.
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|---|---|
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Change From Baseline in Central Retinal Lesion Thickness (CRT) as Measured by Optical Coherence Tomography (OCT) at Day 29
|
37.91 Microns
Standard Deviation 89.692
|
PRIMARY outcome
Timeframe: Baseline (Day -3 to -1) and Day 29Population: ITT Population. Only those participants with data available at the indicated time point were analyzed. OC dataset was used for analysis.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=13 Participants
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.
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|---|---|
|
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
|
0.07 Count of letters
Standard Deviation 9.973
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SECONDARY outcome
Timeframe: Baseline (Week -3 to -1) Up to Follow-up (Day 102)Population: ITT Population. Only those participants available at the specified time points were analyzed. OC dataset was used for analysis.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
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|---|---|
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Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time
CRLT at Week 1
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-3.97 Microns
Standard Deviation 93.420
|
|
Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time
CRLT at Week 2
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-6.39 Microns
Standard Deviation 93.420
|
|
Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time
CRLT at Week 3
|
15.15 Microns
Standard Deviation 86.646
|
|
Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time
CRLT at Week 4
|
31.72 Microns
Standard Deviation 88.289
|
|
Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time
CRLT at Week 6
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51.22 Microns
Standard Deviation 84.679
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|
Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time
CRLT at Week 8
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15.48 Microns
Standard Deviation 82.304
|
|
Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time
CRLT at Week 12
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-1.57 Microns
Standard Deviation 75.216
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Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time
CRLT at Follow-up
|
-8.42 Microns
Standard Deviation 91.346
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SECONDARY outcome
Timeframe: Baseline (Week -3 to -1) Up to Follow-up (Day 102)Population: ITT Population. Only those participants available at the specified time points were analyzed. OC dataset was used for analysis.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
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|---|---|
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Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
SR fluid thickness at Week 1
|
-34.79 Microns
Standard Deviation 70.781
|
|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
SR fluid thickness at Week 2
|
-29.32 Microns
Standard Deviation 71.654
|
|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
SR fluid thickness at Week 3
|
-0.22 Microns
Standard Deviation 67.074
|
|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
SR fluid thickness at Week 4
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5.69 Microns
Standard Deviation 67.938
|
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Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
SR fluid thickness at Week 6
|
28.05 Microns
Standard Deviation 67.192
|
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Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
SR fluid thickness at Week 8
|
35.25 Microns
Standard Deviation 64.689
|
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Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
SR fluid thickness at Week 12
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1.72 Microns
Standard Deviation 57.734
|
|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
SR fluid thickness at Follow-up
|
8.43 Microns
Standard Deviation 70.329
|
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Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
PED thickness at Week 1
|
4.01 Microns
Standard Deviation 56.669
|
|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
PED thickness at Week 2
|
4.47 Microns
Standard Deviation 56.669
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Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
PED thickness at Week 3
|
14.00 Microns
Standard Deviation 53.040
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|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
PED thickness at Week 4
|
7.16 Microns
Standard Deviation 54.843
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|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
PED thickness at Week 6
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37.93 Microns
Standard Deviation 49.035
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|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
PED thickness at Week 8
|
36.57 Microns
Standard Deviation 46.786
|
|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
PED thickness at Week 12
|
-32.68 Microns
Standard Deviation 46.509
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|
Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time
PED thickness at Follow-up
|
-19.04 Microns
Standard Deviation 56.214
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SECONDARY outcome
Timeframe: Baseline (Week -3 to -1) Up to Follow-up (Day 102)Population: ITT Population. Only those participants available at the specified time points were analyzed. OC dataset was used for analysis.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
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|---|---|
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Change From Baseline in BCVA Over Time
Follow-up
|
-5.49 Letters
Standard Deviation 10.388
|
|
Change From Baseline in BCVA Over Time
Week 1
|
0.26 Letters
Standard Deviation 11.015
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Change From Baseline in BCVA Over Time
Week 2
|
0.26 Letters
Standard Deviation 11.015
|
|
Change From Baseline in BCVA Over Time
Week 3
|
-1.47 Letters
Standard Deviation 9.927
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Change From Baseline in BCVA Over Time
Week 4
|
0.07 Letters
Standard Deviation 9.973
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Change From Baseline in BCVA Over Time
Week 6
|
1.76 Letters
Standard Deviation 9.345
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Change From Baseline in BCVA Over Time
Week 8
|
0.63 Letters
Standard Deviation 8.912
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Change From Baseline in BCVA Over Time
Week 12
|
-0.85 Letters
Standard Deviation 8.069
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SECONDARY outcome
Timeframe: Baseline (Day -3 to -1) and Day 29Population: ITT Population. Only those participants with data available at the indicated time point were analyzed. OC dataset was used for analysis.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=13 Participants
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.
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|---|---|
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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
CNV Size at Week 4
|
1.38 millimeter square
Standard Deviation 2.902
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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
CNV total lesion complex size at Week 4
|
1.37 millimeter square
Standard Deviation 2.892
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SECONDARY outcome
Timeframe: Day 29Population: ITT Population. Only those participants with data available at the indicated time point were analyzed. OC dataset was used for analysis.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=13 Participants
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.
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|---|---|
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Number of Participants With Change in Charactertsics (Atrophy, Pigment, SR Hemorrhage, IR Hemorrhage, SR Fluid and Fibrosis) as Measured by FP
Fibrosis at Week 4
|
1 Participants
|
|
Number of Participants With Change in Charactertsics (Atrophy, Pigment, SR Hemorrhage, IR Hemorrhage, SR Fluid and Fibrosis) as Measured by FP
Atrophy at Week 4
|
0 Participants
|
|
Number of Participants With Change in Charactertsics (Atrophy, Pigment, SR Hemorrhage, IR Hemorrhage, SR Fluid and Fibrosis) as Measured by FP
Pigment at Week 4
|
12 Participants
|
|
Number of Participants With Change in Charactertsics (Atrophy, Pigment, SR Hemorrhage, IR Hemorrhage, SR Fluid and Fibrosis) as Measured by FP
Heme (SR) at Week 4
|
10 Participants
|
|
Number of Participants With Change in Charactertsics (Atrophy, Pigment, SR Hemorrhage, IR Hemorrhage, SR Fluid and Fibrosis) as Measured by FP
Heme (IR) at Week 4
|
1 Participants
|
|
Number of Participants With Change in Charactertsics (Atrophy, Pigment, SR Hemorrhage, IR Hemorrhage, SR Fluid and Fibrosis) as Measured by FP
SR fluid at Week 4
|
13 Participants
|
SECONDARY outcome
Timeframe: Up to follow-up (Day 102)Population: Safety Population comprised of any participant who received at least one dose of study medication.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
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|---|---|
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Number of Participants Who Received Rescue Medication
|
9 Participants
|
SECONDARY outcome
Timeframe: Until Follow-up (Day 102)Population: Safety Population.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
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|---|---|
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Number of Participants With Ocular Adverse Events (AEs), Non-ocular AEs, Serious Ocular AEs and Serious Non-ocular AEs
Any Ocular AE
|
8 Participants
|
|
Number of Participants With Ocular Adverse Events (AEs), Non-ocular AEs, Serious Ocular AEs and Serious Non-ocular AEs
Any Ocular SAE
|
0 Participants
|
|
Number of Participants With Ocular Adverse Events (AEs), Non-ocular AEs, Serious Ocular AEs and Serious Non-ocular AEs
Any Non-Ocular AE
|
9 Participants
|
|
Number of Participants With Ocular Adverse Events (AEs), Non-ocular AEs, Serious Ocular AEs and Serious Non-ocular AEs
Any Non-Ocular SAE
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Follow-up (Day 102)Population: Safety Population.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
|
|---|---|
|
Number of Participants With Values of Potential Clinical Concern for Ocular Assessments on General Ophthalmic Examination
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Follow-up (Day 102)Population: Safety Population
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
|
|---|---|
|
Number of Participants With Vital Sign Data of Potential Clinical Concern
Systolic blood pressure
|
2 Participants
|
|
Number of Participants With Vital Sign Data of Potential Clinical Concern
Diastolic blood pressure
|
0 Participants
|
|
Number of Participants With Vital Sign Data of Potential Clinical Concern
Heart rate
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Follow-up (Day 102)Population: Safety population.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
|
|---|---|
|
Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern
Glucose high
|
1 Participants
|
|
Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern
Carbon dioxide low
|
2 Participants
|
|
Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern
Lymphocyte low
|
1 Participants
|
|
Number of Participants With Clinical Chemistry and Hematology Data of Potential Clinical Concern
Platelet count low
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to Follow-up (Day 102)Population: Safety Population. Only those participants available at the specified time points were analyzed,
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
|
|---|---|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Red blood cells 3-5 at Week 2
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Red blood cells 0-1 at Week 4
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Red blood cells 1-3 at Week 4
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Red blood cells 25-50 at Week 4
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Red blood cells 1-3 at Follow-up
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Red blood cells 5-10 at Follow-up
|
2 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
White blood cells 3-5 at Week 2
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
White blood cells 1-3 at Week 4
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
White blood cells 5-10 at Week 4
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
White blood cells 10-15 at Follow-up
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
White blood cells 50-100 at Follow-up
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Urine protein 2+ at Week 4
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Urine protein 1+ at Week 12
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Urine protein 2+ at Week 12
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Urine protein 1+ at Follow-up
|
1 Participants
|
|
Number of Participants With Abnormal Urinalysis Data by Urine Microscopy and Dipstick Analysis
Urine protein 3+ at Follow-up
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to Week 12Population: 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.
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.
Outcome measures
| Measure |
Pazopanib 10 mg/mL QID
n=19 Participants
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.
|
|---|---|
|
Summary of Plasma Pazonib Concentration
Week 2
|
279.0 nanograms per milliliter
Standard Deviation 171.66
|
|
Summary of Plasma Pazonib Concentration
Week 3
|
323.9 nanograms per milliliter
Standard Deviation 216.77
|
|
Summary of Plasma Pazonib Concentration
Week 4
|
360.5 nanograms per milliliter
Standard Deviation 215.80
|
|
Summary of Plasma Pazonib Concentration
Week 6
|
498.0 nanograms per milliliter
Standard Deviation NA
Standard could was not computed as a single participant was analyzed.
|
|
Summary of Plasma Pazonib Concentration
Week 8
|
150.0 nanograms per milliliter
Standard Deviation NA
Standard could was not computed as a single participant was analyzed.
|
|
Summary of Plasma Pazonib Concentration
Week 12
|
255.3 nanograms per milliliter
Standard Deviation 170.06
|
Adverse Events
Pazopanib 10 mg/mL QID
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Pazopanib 10 mg/mL QID
n=19 participants at risk
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.
|
|---|---|
|
Eye disorders
Age-related macular degeneration
|
10.5%
2/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Eye disorders
Macular oedema
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Eye disorders
Ocular Hypertension
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Eye disorders
Retinal haemorrhage
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Eye disorders
Vitreous floaters
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
General disorders
Instillation site pain
|
15.8%
3/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Gastrointestinal disorders
Nausea
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Gastrointestinal disorders
Oesophageal obstruction
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Infections and infestations
Tooth infection
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Infections and infestations
Urinary tract infection
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Injury, poisoning and procedural complications
Skeletal injury
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Investigations
Platelet count decreased
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Investigations
Protein urine present
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Investigations
Red blood cells urine positive
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Investigations
Urine protein/creatinine ratio increased
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Musculoskeletal and connective tissue disorders
Torticollis
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Psychiatric disorders
Depression
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Respiratory, thoracic and mediastinal disorders
Dyshponia
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
|
Vascular disorders
Hypertension
|
5.3%
1/19 • Up to Follow-up (Day 102)
Safety population was used for analysis.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER