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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01154062
First received: June 29, 2010
Last updated: June 9, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Macular Degeneration
Drug: Pazopanib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Exploratory Efficacy and Pharmacodynamics of Oral Pazopanib Administered for 28 Days to Neovascular Age-related Macular Degeneration Patients

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety endpoints include complete ophthalmic examination, visual acuity, vital signs (heart rate and blood pressure), clinical laboratory tests, clinical monitoring and adverse event reporting [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: August 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: low dose
Pazopanib tablet
Drug: Pazopanib
Pazopanib tablet

Detailed Description:

This is a multi-center, open label study of pazopanib administered for 28 days in adult patients with subfoveal CNV due to neovascular AMD. The primary aim is to evaluate safety and tolerability in patients with neovascular AMD and a secondary aim is to evaluate pharmacokinetics and pharmacodynamics. This study does not include a control treatment group (e.g. placebo or active comparator), and instead will be benchmarked to visual acuity and OCT changes observed following treatment with other anti-angiogenic agents in a similar patient population over the same treatment period.

All subjects will receive tablets administered once daily. Subjects will be screened within eight days prior to treatment assignment and initiation of study treatment. The duration of treatment will be 28 days, and subjects will participate in a baseline and four subsequent weekly study visits during the treatment phase. Subjects will also return for a follow-up visit approximately two weeks after last dose of study medication.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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%).

Exclusion Criteria:

  • 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.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result 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).

Medical history or unresolved medical condition, for example:

  • Uncontrolled Diabetes Mellitus, with hemoglobin A1c (HbA1c) > 10%
  • Myocardial infarction or stroke within 6 months of screening
  • Active bleeding disorder
  • Major surgery within 3 months of screening
  • Hepatic impairment
  • Clinically relevant thyroid disease

    • Uncontrolled hypertension, based on criteria provided in Section 4.4.1.2.
    • Subject has a history within the past 2 years of alcohol, substance abuse, or psychiatric disorder likely to confound the efficacy or safety assessments. A history of known HIV infection.
    • Use of prohibited medications listed in Section 9.2 within the restricted timeframe relative to the first dose of study medication.
    • 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.
    • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01154062

Locations
United States, California
GSK Investigational Site
Beverly Hills, California, United States, 90211
GSK Investigational Site
Sacramento, California, United States, 95819
GSK Investigational Site
Sacramento, California, United States, 95841
United States, Florida
GSK Investigational Site
Winter Haven, Florida, United States, 33880
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46290
United States, Michigan
GSK Investigational Site
Grand Rapids, Michigan, United States, 49525
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78705
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01154062     History of Changes
Other Study ID Numbers: 114155
Study First Received: June 29, 2010
Last Updated: June 9, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
age-related macular degeneration
pazopanib
choroidal neovascularization
GW786034

Additional relevant MeSH terms:
Macular Degeneration
Wet Macular Degeneration
Eye Diseases
Retinal Degeneration
Retinal Diseases

ClinicalTrials.gov processed this record on October 22, 2014