Age-related macular degeneration (AMD) MedDRA version: 14.0 Level: PT Classification code 10025409 Term: Macular degeneration System Organ Class: 10015919 - Eye disorders
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Consent: Subject understands the procedures, agrees to participate in the study (including participation in the CFH Y402H pharmacogenetic research), and has signed and dated the informed consent form prior to the initiation of any study-related activities. If the subject is unable to read the consent form due to visual impairment then the consent must be read to the subject verbatim by the person administering the consent, a family member, or legally acceptable representative. (Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations, and ethics committee policy.) 2. Age-related macular degeneration: For each subject enrolled in the study, only one eye (study eye) will be treated, and eligibility criteria apply to the study eye. All of the following characteristics are required and must be confirmed by the central reading center: • CNV caused by AMD that extends under the geometric center of the foveal avascular zone • Center subfield thickness (inclusive of subretinal fluid) > 320 microns on OCT [SPECTRALIS (Heidelberg)] • Total lesion area ?12 disc areas on fluorescein angiography, where the lesion complex includes CNV, blood, blocked fluorescence not from blood, and serous detachment of the retinal pigment epithelium • CNV comprises ? 50% of lesion area • classic CNV comprises 40 MIU/mL and estradiol 1.5xULN is acceptable, if bilirubin is fractionated and direct bilirubin is < 35%). 8. QT interval: Subject has a QTcF value < 450 msec, or < 480 msec for subjects with Bundle Branch Block. [Note: subjects with paced rhythms may be considered pending discussion with the medical monitor.] Specific information regarding warnings, precautions, contraindications, adverse events, and other pe
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: Study Eye: 1. Additional eye disease in the study eye that could compromise best-corrected visual acuity (e.g. glaucoma with documented visual field loss, clinically significant diabetic retinopathy, ischemic optic neuropathy, infection or retinitis pigmentosa) 2. CNV in the study eye due to other causes unrelated to age-related macular degeneration 3. Presence of retinal angiomatous proliferation (RAP) in the study eye, as determined by the investigator (confirmation by indocyanine green angiography is not required) 4. Geographic atrophy involving the center of the fovea in the study eye 5. Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation of the fundus for photographs, fluorescein angiography and spectral-domain OCT 6. Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD 7. Presence of an RPE tear in the study eye 8. Aphakia or total absence of the posterior capsule (Yttrium aluminum garnet (YAG) capsulotomy permitted) in the study eye 9. History of vitrectomy in the study eye 10. Intraocular surgery in the study eye within 3 months prior to treatment 11. Any previous treatment in the study eye for neovascular AMD, approved or investigational Fellow Eye: 12. Current intravitreal anti-VEGF therapy in the fellow eye 13. Best-corrected visual acuity score by electronic ETDRS 25 mmHg) despite treatment with anti-glaucoma medication. 15. A known, positive test for Hepatitis B surface antigen or Hepatitis C antibody within 3 months of screening 16. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) 17. Active bleeding disorder or a history of hemoptysis, cerebral or clinically significant gastrointestinal hemorrhage within 6 months of screening 18. Significant uncontrolled or unstable cardiovascular, nervous system, pulmonary, renal, endocrine, or gastrointestinal disease for example: • Uncontrolled diabetes mellitus, with hemoglobin A1c (HbA1c) > 10% • Myocardial infarction or stroke within 6 months of screening • Major surgery within 3 months of screening • Clinically relevant thyroid disease 19. Uncontrolled hypertension: Systolic blood pressure > 160 mmHg Diastolic blood pressure > 100 mmHg Note: Initiation or adjustment of antihypertensive medications is permitted prior to study entry provided the referenced criteria are met (See Section 4.4.3). 20. Subject has a history within the past 2 years of alcohol or substance abuse, or psychiatric disorder likely to confound the efficacy or safety assessments. 21. Known HIV infection 22. Within 6 months prior to the Screening Visit, use of any systemically administered anti angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib), approved or investigational 23. Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol) 24. Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of the start of treatment 25. Use of prohibited m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objectives: • To assess the effect of pazopanib eye drops on central retinal thickness • To evaluate the effect of pazopanib eye drops on visual acuity ;Secondary Objective: Secondary Objectives: • To assess the effect of pazopanib eye drops on central retinal lesion thickness and retinal morphology • To evaluate the safety and tolerability of pazopanib eye drops • To determine steady-state plasma concentrations with topical ocular administration Exploratory Objectives: • To explore the relationship between plasma concentrations and the effect of pazopanib eyes drops on the reduction of retinal edema and improvements in visual acuity;Primary end point(s): • Change from baseline in central retinal thickness over time, as measured by OCT, and change from baseline in BCVA over time, as measured by the number of letters determined by EVA, with the changes after 28 days of treatment (Week 4 [Day 29] Visit) being the primary focus ;Timepoint(s) of evaluation of this end point: Screening (days -8- to -2 before baseline) to Day 29. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): OCT endpoints: • Change from baseline in central retinal lesion thickness over time • Change in intraretinal (IR) or subretinal (SR) fluid, intraretinal cysts, or serous retinal pigment epithelial detachment (PED) over time Visual acuity endpoints: • Visual acuity response over time (proportion of subjects with BCVA of various 5-letter thresholds gained or lost from baseline; proportion of subjects whose BCVA did not decline from baseline) Fluorescein angiographic and fundus photographic endpoints: • Change from baseline in the area of CNV • Change from baseline in the area of the CNV lesion complex (i.e., CNV, blood, PED, and fibrosis) Rescue endpoints: • Proportion of patients who receive rescue treatment • Time to rescue injection Safety endpoints: • Non-serious adverse events (AEs) and serious adverse events (SAEs) (both ocular and non-ocular AEs) • Ocular assessments on general ophthalmic examination • Vital signs • Laboratory analytes including hematology and clinical chemistries • Urinalysis Pharmacokinetic endpoint: • Plasma pazopanib concentrations Exploratory endpoints: • Pharmacokinetic endpoint: Response as related to plasma pazopanib concentration • Pharmacogenetic endpoint: Response as related to the status of genetic polymorphisms including the CFH Y402H polymorphism;Timepoint(s) of evaluation of this end point: Screening (days -8- to -2 before baseline) to Day 29. | — |
Countries
Germany, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline
Outcome results
None listed