Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01134055
Registration number
NCT01134055
Ethics application status
Date submitted
27/05/2010
Date registered
31/05/2010
Date last updated
8/01/2018
Titles & IDs
Public title
Dose Ranging Study of Pazopanib to Treat Neovascular Age-Related Macular Degeneration
Query!
Scientific title
MD7110852, A Phase 2b Dose-Ranging Study of Pazopanib Eye Drops Versus Ranibizumab Intravitreal Injections for the Treatment of Neovascular Age-Related Macular Degeneration
Query!
Secondary ID [1]
0
0
110852
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Macular Degeneration
0
0
Query!
Condition category
Condition code
Eye
0
0
0
0
Query!
Diseases / disorders of the eye
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - pazopanib eye drops
Treatment: Drugs - placebo
Other interventions - ranibizumab intravitreal injection
Experimental: investigational arm 1 - 5 mg/mL pazopanib eye drops TID with allowance for as-needed ranibizumab injection
Experimental: investigational arm 2 - 5 mg/mL pazopanib eye drops QID with allowance for as-needed ranibizumab injection
Experimental: investigational arm 3 - 10 mg/mL pazopanib eye drops BID with allowance for as-needed ranibizumab injection
Experimental: investigational arm 4 - 10 mg/mL pazopanib eye drops TID with allowance for as-needed ranibizumab injection
Experimental: investigational arm 5 - 10 mg/mL pazopanib eye drops QID with allowance for as-needed ranibizumab injection
Placebo Comparator: placebo control arm - Placebo eye drops QID with allowance for as-needed ranibizumab injection
Active Comparator: active open-label control arm - Ranibizumab intravitreal injection every 4 weeks
Treatment: Drugs: pazopanib eye drops
A tyrosine kinase inhibitor of multiple receptors including vascular endothelial growth factor receptors and platelet-derived growth factor receptors.
Treatment: Drugs: placebo
placebo eye drops
Other interventions: ranibizumab intravitreal injection
Humanized recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Intervention code [2]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Change From Baseline in Best-corrected Visual Acuity (BCVA) as Measured by the Number of Letters Read on the Early Treatment of Diabetic Retinopathy Study (ETDRS) Grading Charts at a Starting Distance of 4 Meters at Week 52
Query!
Assessment method [1]
0
0
BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Query!
Timepoint [1]
0
0
Day 1 and 52 weeks
Query!
Secondary outcome [1]
0
0
Percentage of Ranibizumab Re-injections Received Over 28 and 52 Weeks
Query!
Assessment method [1]
0
0
The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection. Injection rate over 52 weeks was computed by taking the number of injections received divided by the number of visits for the participant. Likewise for 28 weeks it was estimated as the number of post baseline injections received divided by the number of post baseline visits at or before the week 28 visit.
Query!
Timepoint [1]
0
0
Up to 52 weeks
Query!
Secondary outcome [2]
0
0
Number of Participants With BCVA Over Time
Query!
Assessment method [2]
0
0
BCVA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters. The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters.
Query!
Timepoint [2]
0
0
Up to Week 52
Query!
Secondary outcome [3]
0
0
Number of Participants Analyzed for Visual Acuity (VA) Response Over Time
Query!
Assessment method [3]
0
0
VA was measured in the study eye using the ETDRS grading charts starting at a test distance of 4 meters.The ETDRS grading chart was of at least 24 to 78 letters. There were seven cut off points in change from baseline visual acuity on ETDRS grading chart which are, 15 to 29, 10 to 14, 5 to 9, -4 to 4, -5 to -9, -10 to -14 and -15 to -29 letters. This outcome measure contains the number of participants who were analyzed for VA response.
Query!
Timepoint [3]
0
0
Week 52
Query!
Secondary outcome [4]
0
0
Change From Baseline in Center Point Thickness (CPT) Over Time
Query!
Assessment method [4]
0
0
CPT was the inner limiting membrane to the beginning of the retinal pigment epithelium (RPE) inclusive of SR fluid. The outer boundary included the outer segment of the photoreceptors and not included the RPE. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study. In amendment 3, inclusion criterion number 5 was revised to remove the required quantitative OCT component. OCT examination was used to supplement FA findings and provided qualitative (presence of SR and/or IR fluid) and quantitative (a CPT that is at least 250 microns) evidence of an active subfoveal lesion. Hence data for pre and post amendment have been provided separately.
Query!
Timepoint [4]
0
0
Baseline and Week 52
Query!
Secondary outcome [5]
0
0
Number of Participants That Met Criteria for Re-injection
Query!
Assessment method [5]
0
0
The investigator interpreted each Week 4 to Week 52 Optical coherence tomography (OCT) scan, BCVA score, and available Fluorescein angiography (FA)/Fundus photography (FP) and re-injected if one or more criteria were met. The criteria were: Evidence of Intraretinal (IR) (with or without cysts) fluid or Subretinal (SR) fluid, a serous retinal pigment epithelial detachment, a notable decline in Visual Acuity, new SR or IR macular hemorrhage that the investigator judges is associated with Choroidal neovascularization, increased lesion size on FA relative to the last angiogram as judged by the investigator or leakage on FA that the investigator judges would benefit from re-injection.
Query!
Timepoint [5]
0
0
Up to Week 52
Query!
Secondary outcome [6]
0
0
Change From Baseline in the Area of Choroidal Neovascularisation (CNV)
Query!
Assessment method [6]
0
0
Choroidal neovascularisation is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Query!
Timepoint [6]
0
0
Day 1, Week 28 and Week 52
Query!
Secondary outcome [7]
0
0
Change From Baseline in the Area of the CNV Lesion Complex (i.e. CNV, Blood, PED, and Fibrosis)
Query!
Assessment method [7]
0
0
CNV is progressive worsening of vision that can cause hemorrhage and exudation, and finally disciform scarring and retinal atrophy. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. If either the baseline or post-randomization value was missing, the change from baseline was set to missing as well. Day 1 values are considered as Baseline in this study.
Query!
Timepoint [7]
0
0
Day 1, Week 28 and Week 52
Query!
Secondary outcome [8]
0
0
Change From Baseline in the Area of Fluorescein Leakage
Query!
Assessment method [8]
0
0
Fluorescein angiograms was performed at the Screening, Week 12, Week 28, and Week 52 Visits. All images, including any that were performed at the investigator's medical discretion, were transferred to the FPRC. Fluorescein was injected intravenously according to usual clinic procedures. Dose response was also examined under different aspects of re-injection, such as time to first injection, the percentage of participants that required an injection by Week 28, as well as the estimation of the probability of reinjection. FA assessments of area of fluorescein leakage, CNV area and area of CNV lesion complex were also examined for dose differentiation.
Query!
Timepoint [8]
0
0
Day 1, Week 28 and Week 52
Query!
Secondary outcome [9]
0
0
Change in Area of Serous Sensory Retinal Detachment (SSRD)
Query!
Assessment method [9]
0
0
This is an Optical coherence tomography (OCT) parameter used to manually measure thickness along any scan. OCT was performed at week 28 and week 52.
Query!
Timepoint [9]
0
0
Day 1, Week 28 and Week 52
Query!
Secondary outcome [10]
0
0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Query!
Assessment method [10]
0
0
An AE is 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 SAE is 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, or is a congenital anomaly/birth defect.
Query!
Timepoint [10]
0
0
Up to 52 Weeks
Query!
Secondary outcome [11]
0
0
Summary of Potentially Clinically Important Findings for Ophthalmic Examinations
Query!
Assessment method [11]
0
0
Opthalmicexaminations were done on Ocular alignment and motility, pupillary function, and visual fields by confrontation. Slit-lamp biomicroscopic examination of the anterior segment structure was performed. Fundus slit-lamp biomicroscopic examination, including use of accessory diagnostic lenses, to view the vitreous, retina (including posterior pole and periphery), macula, vasculature, and optic nerve was also performed. These examinations were performed on the study eye (SE) and the Fellow eye (FE). Participants with abnormal findings are listed here.
Query!
Timepoint [11]
0
0
Up to Week 52
Query!
Secondary outcome [12]
0
0
Summary of Intraocular Pressure Exam Findings
Query!
Assessment method [12]
0
0
Intraocular pressure (IOP) measurement was done with Goldmann tonometer. Intraocular pressure was measured prior to dilating the pupil and, to account for diurnal variation, at approximately the same time of day for every visit.
Query!
Timepoint [12]
0
0
Up to week 52
Query!
Secondary outcome [13]
0
0
Number of Participants With Vital Sign Values Outside of Clinical Concern Range
Query!
Assessment method [13]
0
0
Vital signs including systolic and diastolic blood pressure and heart rate were measured throughout the study. Number of participants with vital signs outside of clinical concern Range were summarized. 'High' denotes above normal range and 'Low' denotes below normal range for all the categories. The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (<85 and >160 millimeter of mercury [mmHg]), diastolic blood pressure (<45 and >100 mmHg) and heart rate (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.
Query!
Timepoint [13]
0
0
Up to Week 52
Query!
Secondary outcome [14]
0
0
Summary of Abnormal Electrocardiogram (ECG) Findings
Query!
Assessment method [14]
0
0
12-Lead ECGs were performed in triplicate and were obtained on Weeks 4 to Week 28 and Week 52. The on-treatment ECGs were used to ascertain any risk of QTc interval prolongation at extremely low pazopanib exposures compared to what was routinely observed in participants with cancer. The on-treatment ECG data collected from participants assigned to one of the control arms also provided ECG background rate data for participants not exposed to pazopanib. Participants with Clinically significant abnormal ECGs are included here.
Query!
Timepoint [14]
0
0
Week 4, Week 28, Week 44 and Week 52
Query!
Secondary outcome [15]
0
0
Summary of Hematology and Clinical Chemistry Parameters Data of Clinical Concern
Query!
Assessment method [15]
0
0
The Laboratory Parameters included Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Amino Transferase (AST), Calcium, Bicarbonate, Creatinine, Glucose, Hemoglobin, Lymphocytes, Platelet count, Potassium, Sodium, Thyroid Stimulating Hormone (TSH), Total Bilirubin, Total Neutrophils, Blood Urea Nitrogen (BUN) and White Blood Cell count (WBC). Number of participants with Laboratory outside of clinical concern Range were summarized here. Data of high and low from the clinical concern range has been provided here. Here 'High' denotes above normal range and 'Low' denotes below normal range for all the categories.
Query!
Timepoint [15]
0
0
Up to Week 52
Query!
Secondary outcome [16]
0
0
Number of Participants With Laboratory Data of Clinical Concern for Urine Protein
Query!
Assessment method [16]
0
0
Urine Samples were collected from Day 1 to Week 28 and Week 52 for analyses. In this dipstick test, the level of protein in urine samples was recorded as negative (Neg), trace (tr), 1+, 2+, and 3+ (the plus sign increases with a higher level of proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). Neg indicated no proteinuria and 3+(high positive) indicated worst proteinuria.
Query!
Timepoint [16]
0
0
Day 1 to Week 28 and Week 52
Query!
Secondary outcome [17]
0
0
Plasma Concentrations of Pazopanib
Query!
Assessment method [17]
0
0
All participants in the eye drop containing arms had a single blood sample drawn for assessment of pazopanib plasma concentration at the Week 4, Week 24 and Week 24. The sample was drawn without restriction for the time interval between blood draw and the last dose of IP eye drops.
Query!
Timepoint [17]
0
0
Week 4, Week 24 and Week 52
Query!
Eligibility
Key inclusion criteria
- Men and women aged =50 years.
- Active subfoveal choroidal neovascularization (CNV) lesion secondary to AMD in study
eye: Total lesion area =12 disc areas with CNV =50% total lesion area.
- Anti-Vascular endothelial growth factor (VEGF) intravitreal injection experienced and
in need of re-treatment.
- Best-corrected visual acuity of at least 24 letters (equates to approximately 20/320
Snellen equivalents or better).
Query!
Minimum age
50
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Prior ocular investigational drug/device for choroidal neovascularization,
photodynamic therapy, radiation, subfoveal or juxtafoveal focal laser
photocoagulation.
- Prior failure to anti-VEGF intravitreal injection therapy.
- Recent ocular investigational drug/device for non-CNV condition.
- Prior ocular surgeries (vitrectomy, scleral buckle, or glaucoma filtering/shunt
surgery). Cataract surgery permitted if =3 months and has posterior chamber
intraocular lens.
- Center-fovea involvement of any of the following: fibrosis, atrophy, serous retinal
pigment epithelial detachment, or retinal pigment epithelial tear.
- CNV in either eye due to other causes.
- Clinical evidence of diabetic retinopathy or diabetic macular edema.
- Recent myocardial infarction or cerebrovascular accident.
- Uncontrolled hypertension in spite of antihypertensive medications.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/06/2010
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/10/2012
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
510
Query!
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Query!
Recruitment hospital [1]
0
0
GSK Investigational Site - Sydney
Query!
Recruitment hospital [2]
0
0
GSK Investigational Site - Melbourne
Query!
Recruitment hospital [3]
0
0
GSK Investigational Site - Nedlands
Query!
Recruitment postcode(s) [1]
0
0
2000 - Sydney
Query!
Recruitment postcode(s) [2]
0
0
2150 - Sydney
Query!
Recruitment postcode(s) [3]
0
0
- Melbourne
Query!
Recruitment postcode(s) [4]
0
0
6009 - Nedlands
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Arizona
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Colorado
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Florida
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Illinois
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Kansas
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Kentucky
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Maryland
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Massachusetts
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Michigan
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
New York
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
North Carolina
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Ohio
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Oregon
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
Pennsylvania
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
Texas
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
Utah
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
Washington
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
Wisconsin
Query!
Country [20]
0
0
Belgium
Query!
State/province [20]
0
0
Bruxelles
Query!
Country [21]
0
0
Belgium
Query!
State/province [21]
0
0
Liège
Query!
Country [22]
0
0
Canada
Query!
State/province [22]
0
0
British Columbia
Query!
Country [23]
0
0
Canada
Query!
State/province [23]
0
0
Nova Scotia
Query!
Country [24]
0
0
Canada
Query!
State/province [24]
0
0
Ontario
Query!
Country [25]
0
0
Denmark
Query!
State/province [25]
0
0
Aarhus
Query!
Country [26]
0
0
Denmark
Query!
State/province [26]
0
0
Glostrup
Query!
Country [27]
0
0
Germany
Query!
State/province [27]
0
0
Baden-Wuerttemberg
Query!
Country [28]
0
0
Germany
Query!
State/province [28]
0
0
Bayern
Query!
Country [29]
0
0
Germany
Query!
State/province [29]
0
0
Nordrhein-Westfalen
Query!
Country [30]
0
0
Germany
Query!
State/province [30]
0
0
Sachsen
Query!
Country [31]
0
0
Germany
Query!
State/province [31]
0
0
Schleswig-Holstein
Query!
Country [32]
0
0
Italy
Query!
State/province [32]
0
0
Friuli-Venezia-Giulia
Query!
Country [33]
0
0
Italy
Query!
State/province [33]
0
0
Lombardia
Query!
Country [34]
0
0
Italy
Query!
State/province [34]
0
0
Piemonte
Query!
Country [35]
0
0
Italy
Query!
State/province [35]
0
0
Veneto
Query!
Country [36]
0
0
Japan
Query!
State/province [36]
0
0
Aichi
Query!
Country [37]
0
0
Japan
Query!
State/province [37]
0
0
Chiba
Query!
Country [38]
0
0
Japan
Query!
State/province [38]
0
0
Fukuoka
Query!
Country [39]
0
0
Japan
Query!
State/province [39]
0
0
Fukushima
Query!
Country [40]
0
0
Japan
Query!
State/province [40]
0
0
Hokkaido
Query!
Country [41]
0
0
Japan
Query!
State/province [41]
0
0
Kagawa
Query!
Country [42]
0
0
Japan
Query!
State/province [42]
0
0
Tokyo
Query!
Country [43]
0
0
Sweden
Query!
State/province [43]
0
0
Linköping
Query!
Country [44]
0
0
Sweden
Query!
State/province [44]
0
0
Stockholm
Query!
Country [45]
0
0
Sweden
Query!
State/province [45]
0
0
Uppsala
Query!
Country [46]
0
0
Sweden
Query!
State/province [46]
0
0
Örebro
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
GlaxoSmithKline
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The purpose of this study is to determine the safety and efficacy of different dosage
regimens of pazopanib eye drops for the treatment of neovascular age-related macular
degeneration.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01134055
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
GSK Clinical Trials
Query!
Address
0
0
GlaxoSmithKline
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01134055
Download to PDF