12 Week Patient Study in Neovascular Age-related Macular Degeneration (AMD)
Condition: Macular Degeneration
MeSH terms: Macular Degeneration
Intervention: pazopanib eye drops
Intervention description: 10 mg/mL (1 drop) four times daily
Intervention MeSH terms: Ophthalmic Solutions
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Age-related Macular Degeneration

Summary:

      The purpose of this 12 week, open-label study is to investigate the safety and efficacy of a
      single dose regimen of pazopanib eye drop for neovascular AMD.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects eligible for enrolment in the study must meet all of the following criteria:

          -  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.)

          -  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 florescence not from blood, and serous detachment of the
             retinal pigment epithelium

          -  CNV comprises < 50% of lesion area

          -  classic CNV comprises < 50% of the lesion area

          -  fibrosis comprises ≤ 25% of lesion area

          -  if no evidence of classic CNV, then presumed to have recent disease progression based
             on deterioration (≥ 5 letter decrease in vision or evidence of growth of a CNV lesion
             on fluorescein angiography ) within the last 3 months or evidence of hemorrhage from
             CNV

          -  Visual acuity: Best-corrected visual acuity score by electronic ETDRS in the study eye
             of between 25 and 73 letters (approximately equivalent to Snellen VA of 20/320 to
             20/32) at screening

          -  Gender and age: Subject is a male or female adult 50 years of age or older.

          -  Non-childbearing potential: Female subject is of non-childbearing potential defined as
             being physiologically incapable of becoming pregnant. This includes any female who is
             post-menopausal (12 months of spontaneous amenorrhea) or who is surgically
             post-menopausal (via documented hysterectomy or bilateral tubal ligation). In
             questionable cases of postmenopausal status, a blood sample with simultaneous follicle
             stimulating hormone (FSH) >40 MIU/mL and estradiol <40 pg/mL (<140 pmol/L) [or
             equivalent values based on local laboratory criteria] is confirmatory. Refer to the
             SPM for more information.

          -  Study Compliance: Subject is able and willing to comply with the study requirements
             and is able and willing to attend all scheduled visits.

          -  Liver function tests: Subject has liver chemistry values that are within normal limits
             or clinically insignificant as evidenced by serum aspartate aminotransferase (AST) and
             alanine aminotransferase (ALT) <2xULN; alkaline phosphatase and bilirubin <1.5xULN
             (isolated bilirubin >1.5xULN is acceptable, if bilirubin is fractionated and direct
             bilirubin is < 35%).

          -  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.]

        Exclusion Criteria:

        Subjects meeting any of the following criteria must not be enrolled in the study:

        Study Eye:

          -  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)

          -  CNV in the study eye due to other causes unrelated to age-related macular degeneration

          -  Presence of retinal angiomatous proliferation (RAP) in the study eye, as determined by
             the investigator (confirmation by indocyanine green angiography is not required)

          -  Geographic atrophy involving the center of the fovea in the study eye

          -  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

          -  Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD

          -  Presence of an RPE tear in the study eye

          -  Aphakia or total absence of the posterior capsule (Yttrium aluminum garnet (YAG)
             capsulotomy permitted) in the study eye

          -  History of vitrectomy in the study eye

          -  Intraocular surgery in the study eye within 3 months prior to treatment

          -  Any previous treatment in the study eye for neovascular AMD, approved or
             investigational

        Fellow Eye:

          -  Current intravitreal anti-VEGF therapy in the fellow eye

          -  Best-corrected visual acuity score by electronic ETDRS < 56 letters in the fellow eye
             at screening

        Concurrent Conditions or Concomitant Medications:

          -  Subject has uncontrolled glaucoma (intraocular pressure > 25 mmHg) despite treatment
             with anti-glaucoma medication.

          -  A known, positive test for Hepatitis B surface antigen or Hepatitis C antibody within
             3 months of screening

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones)

          -  Active bleeding disorder or a history of hemoptysis, cerebral or clinically
             significant gastrointestinal hemorrhage within 6 months of screening

          -  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

          -  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).

          -  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.

          -  Known HIV infection

          -  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

          -  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)

          -  Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of the
             start of treatment

          -  Use of prohibited medications within the restricted timeframe relative to the start of
             study medication (See Section 5.5.2)

          -  Use of an investigational drug within 30 days of screening

          -  History of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that, in the opinion of the investigator or GSK
             Medical Monitor, contraindicates their participation

          -  A condition or situation, which, in the opinion of the investigator, may result in
             significant risk to the patient, confound the study results or interfere significantly
             with participation