A Study to Evaluate Pazopanib Tablets in Patients Who Have Neovascular Age-related Macular Degeneration

NCT01154062 | Completed Phase 1

• 1 other identifier: 114155
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 7

Brief Summary

A study to evaluate pazopanib tablets in male and female adults of non-child bearing potential with subfoveal CNV due to neovascular AMD. The goal is to assess safety and how well the subjects tolerate the drug. The study will also look at how the body breaks down and metabolizes the drug. All subjects will start the study up to 8 days prior to receiving drug. Once started subjects will take one tablet each day for 28 days. A follow up visit will occur approximately 2 weeks after drug is stopped.

Conditions

Macular Degeneration

Keywords

age-related macular degeneration; pazopanib; choroidal neovascularization; GW786034

Outcome Measures

Primary Outcomes (1)

• Safety endpoints include complete ophthalmic examination, visual acuity, vital signs (heart rate and blood pressure), clinical laboratory tests, clinical monitoring and adverse event reporting

  1 month

Secondary Outcomes (1)

• Changes in visual acuity, central retinal thickness, central retinal lesion thickness, retinal morphology, neovascular size, lesion size, and characteristics by fluoresceinangiography and fundus photography. Also, (CL/F), (V/F), (Ka), and (Cτ)

  1 month

Study Arms (1)

low dose

EXPERIMENTAL

Pazopanib tablet

Drug: Pazopanib

Interventions

Pazopanib DRUG

Pazopanib tablet

low dose

Eligibility Criteria

• Age: 50 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age-related macular degeneration patients diagnosed with subfoveal choroidal neovascularization in the study eye, with all of the following characteristics required and confirmed by a central reading center:
• CNV caused by AMD that extends under the geometric center of the foveal avascular zone
• CNV comprises ≥ 50% of lesion area
• Total lesion area no greater than 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
• classic CNV comprises \<50% of the lesion area
• fibrosis comprises ≤ 25% of lesion area
• Center subfield \> 320 microns on SD-OCT (inclusive of subretinal fluid)
• if no evidence of classic CNV, then presumed to have recent disease progression because of deterioration (≥ 5 letter decrease in vision or evidence of growth of a CNV lesion on fluorescein angiography ) within last 3 months or evidence of hemorrhage from CNV
• Best-corrected ETDRS visual acuity score in the study eye of between 25 and 73 letters (approximately equivalent to Snellen VA of 20/320 to 20/32) at screening.
• Male or female ≥ 50 years of age.
• A female subject is eligible to participate if she is of non-childbearing potential defined as either pre-menopausal with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases of postmenopausal status a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) or value consistent with local laboratory recommended value is confirmatory.
• Subject is willing and able to return for all study visits, and is willing and able to comply with all protocol requirements and procedures.
• Subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 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 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.)
• QTcF \<450msec; or QTcF\<480msec in subjects with Bundle Branch Block.
• AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).

You may not qualify if:

• 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.
• The 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 SD-OCT.
• Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD. Any previous treatment in the study eye for neovascular AMD, approved or investigational.
• Current intravitreal anti-VEGF therapy in the fellow eye.
• 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.
• Intraocular surgery in the study eye within 3 months of dosing.
• 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.
• Presence of RPE tear in the study eye.
• Subject has uncontrolled glaucoma (intraocular pressure \>25 mmHg) despite treatment with anti-glaucoma medication.
• 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, nicotinic acid, and ethambutol).
• Use of systemic steroids (\>10 mg prednisone or equivalent/day) within 14 days of first dose.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (7)

GSK Investigational Site

Beverly Hills, California, 90211, United States

Location

GSK Investigational Site

Sacramento, California, 95819, United States

Location

GSK Investigational Site

Sacramento, California, 95841, United States

Location

GSK Investigational Site

Winter Haven, Florida, 33880, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46290, United States

Location

GSK Investigational Site

Grand Rapids, Michigan, 49525, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

Related Publications (1)

• McLaughlin MM, Paglione MG, Slakter J, Tolentino M, Ye L, Xu CF, Suttle AB, Kim RY. Initial exploration of oral pazopanib in healthy participants and patients with age-related macular degeneration. JAMA Ophthalmol. 2013 Dec;131(12):1595-601. doi: 10.1001/jamaophthalmol.2013.5002.

  PMID: 24113783 DERIVED

Related Links

• Results for study 114155 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Macular Degeneration; Choroidal Neovascularization

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2010
• First Posted: June 30, 2010
• Study Start: August 16, 2010
• Primary Completion: April 29, 2011
• Study Completion: April 29, 2011
• Last Updated: November 9, 2017

Record last verified: 2017-11

Locations

US (7)