Clinical trial NCT00733304: An Extension to Study MD7108240
Official title: An Extension Study to Protocol MD7108240: Pazopanib Eye Drops in Subjects With Neovascular Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Macular Degeneration
Keywords: age-related macular degeneration (AMD)
choroidal neovascularization (CNV)
vascular endothelial growth factor (VEGF)
pazopanib
angiogenesis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-08-13
Enrollment: 42
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a two month study to allow continued treatment with pazopanib eye drops. Study may be extended to 5 months.


Eligibility criteria: Inclusion Criteria:

* Subjects who participated in Phase IIa study MD7108240 and who did not experience AMD disease progression requiring rescue therapy during pazopanib treatment or require discontinuation of pazopanib eye drops for safety reasons
* Best-corrected ETDRS visual acuity in the study eye of 23 letters (20/320 or 4/63) or better at screening.
* QTcB or QTcF \< 450msec; or QTc \< 480msec in subjects with Bundle Branch Block.
* 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. If the subject is unable to provide written informed consent due to visual impairment, then written informed consent on behalf of the subject must be provided by a legally acceptable representative. (Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations and ethics committee policy.)

Exclusion Criteria:

* Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation of the fundus for photographs, fluorescein angiography and OCT.
* Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD.
* Intraocular surgery in the study eye within 3 months of dosing.
* Use of topical ocular medications (other than pazopanib) in the study eye within 7 days of first dose of investigational product or expected use of topical ocular medications during the treatment period, with the exception of artificial tears.
* Current 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).
* An unwillingness to refrain from wearing contact lenses starting from the screening visit, through the follow-up visit
* ALT or AST above the upper limit of normal or total bilirubin ≥ 1.5 times the upper limit of normal at baseline. Note: Laboratory tests outside of the normal range may be repeated at the discretion of the Investigator.
* Medical history or condition:
* Uncontrolled Diabetes Mellitus, with hemoglobin A1c (HbA1c) \> 10%.
* Myocardial infarction or stroke within 6 months of screening.
* Active bleeding disorder.
* Major surgery within 1 month of screening.
* Hepatic impairment.
* Uncontrolled hypertension, based on criteria provided in the protocol. Note: Initiation or adjustment of antihypertensive medications is permitted prior to study entry provided the referenced criteria are met.
* Use of prohibited medications listed in the protocol within the restricted timeframe relative to the first dose of study medication.
* A condition or situation which, in the opinion of the investigator, may result in significant risk to the subject, confound the study results or interfere significantly with participation.

Primary outcomes:
measure: Change From Baseline (Day 1) in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Period
timeFrame: Baseline (Day 1) and approximately up to 6 months
measure: Change From Baseline (Day 1) in Heart Rate Over Period
timeFrame: Baseline (Day 1) and approximately up to 6 months
measure: Change From Baseline (Day 1) in Albumin and Hemoglobin Over Period
timeFrame: Baseline (Day 1), Month 2, 5 and approximately up to Month 6
measure: Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferases (ALT), and Aspartate Aminotransferases (AST) Over Period
timeFrame: Baseline (Day 1) and approximately up to 6 months
measure: Change From Baseline (Day 1) in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, and White Blood Cell Count Over Period
timeFrame: Baseline (Day 1) and approximately up to 6 months
measure: Change From Baseline (Day 1) in Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Over Period
timeFrame: Baseline (Day 1) and approximately up to 6 months
measure: Change From Baseline (Day 1) in Direct Bilirubin, Total Bilirubin, and Creatinine Over Period
timeFrame: Baseline (Day 1) and approximately up to 6 months
measure: Change From Baseline in Calcium, Chloride, Carbon di Oxide Equivalent Content, Glucose, Potassium, Sodium, and Urea Blood Urea Nitrogen (BUN) Over Period
timeFrame: Baseline (Day 1) and approximately up to 6 months
measure: Change From Baseline (Day 1) in Mean Corpuscular Volume (MCV) Over Period
timeFrame: Baseline (Day 1) and approximately up to 6 months
measure: Change From Baseline (Day 1) in Intra-ocular Pressure Assessment Over Period
timeFrame: Baseline (Day 1) and approximately up to 6 months
measure: Number of Participants With Blood Occult, Urine Glucose, Urine Ketones, and Urine Proteins by Dip Stick Analysis
timeFrame: Approximately up to 6 months (up to follow-up)
measure: Number of Participants With Adverse Events (AEs)and Serious Adverse Events (SAEs)
timeFrame: Approximately up to 6 months
measure: Number of Participants With Abnormal Visual Acuity of Potential Clinical Concern (PCI)
timeFrame: Approximately up to 6 months
measure: Number of Participants With Abnormal Pupil Examination of PCI
timeFrame: Up to follow-up (approximately 6 months)
measure: Number of Participants With Abnormal Conjunctival Examination of PCI
timeFrame: Up to follow-up (approximately 6 months)
measure: Number of Participants With Abnormal Anterior Chamber Examination of PCI
timeFrame: Approximately up to 6 months
measure: Number of Participants With Abnormal Corneal Examination of PCI
timeFrame: Approximately up to 6 months
measure: Number of Participants With Abnormal Lens Opacity of PCI Using Age Related Eye Disease Study (AREDS) Scale
timeFrame: Approximately up to 6 months
measure: Number of Participants With Abnormal Tear Films of PCI
timeFrame: Approximately up to 6 months
measure: Number of Participants With Any Grade 2 Plus Worsening of Meibomian Gland Function
timeFrame: Approximately up to 6 months
measure: Number of Participants With Abnormal (Dilated) Fundus Examination
timeFrame: Approximately up to 6 months
Secondary outcomes:
measure: Change From Baseline (Screening Visit) in BCVA at Month 2 and 5
timeFrame: From Baseline (screening visit), Month 2, and Month 5
measure: Change From Baseline (Screening Visit) in Optical Coherence Tomography (OCT) Central Subfield Over 5 Months
timeFrame: From Baseline (Screening visit) and up to 5 months
measure: Change in Neo-vascular Size and Lesion Size Over Period
timeFrame: Up to 6 weeks
measure: Number of Participants With Lesion Types Over Period
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Winter Haven
country: United States
facility: GSK Investigational Site
state: Florida
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: GSK Investigational Site
state: Michigan
city: Grand Rapids
country: United States
facility: GSK Investigational Site
state: Michigan
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Sydney
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Sydney
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Perth
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Firenze
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Padova
country: Italy
facility: GSK Investigational Site
state: Veneto
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: