0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation | Clinical Trial

Initial Exploration of Oral Pazopanib in Healthy Participants and Patients With Age-Related Macular Degeneration

Megan M. McLaughlin, MS1; Marcella G. Paglione, PharmD1; Jason Slakter, MD2; Michael Tolentino, MD3; Li Ye, MS1; Chun-Fang Xu, PhD4; A. Benjamin Suttle, PhD5; Robert Y. Kim, MD1
[+] Author Affiliations
1GlaxoSmithKline, King of Prussia, Pennsylvania
2Vitreous Retina Macula Consultants of New York, New York
3Center for Retina and Macular Disease, Winter Haven, Florida
4GlaxoSmithKline, Stevenage, England
5GlaxoSmithKline, Research Triangle Park, North Carolina
JAMA Ophthalmol. 2013;131(12):1595-1601. doi:10.1001/jamaophthalmol.2013.5002.
Text Size: A A A
Published online

Importance  Neovascular age-related macular degeneration (AMD) is managed with intravitreal anti–vascular endothelial growth factor therapy; however, the burden of care is high and alternate approaches could be beneficial.

Objective  To identify an acceptable dose of oral pazopanib for investigation in AMD.

Design, Setting, and Participants  Fourteen-day, placebo-controlled, dose-rising study in 72 healthy participants and 28-day phase 2a open-label study in 15 patients with subfoveal choroidal neovascularization secondary to AMD at a clinical unit for healthy participants and outpatient for patients with AMD.

Intervention  Oral pazopanib tablets, 5 to 30 mg daily (healthy participants) and 15 mg daily (patients with AMD).

Main Outcomes and Measures  Safety, pharmacokinetics, best-corrected visual acuity, central retinal lesion thickness, and central retinal thickness at day 29.

Results  Oral pazopanib up to 30 mg daily in healthy participants and 15 mg daily in patients with AMD was well tolerated. Six of 15 patients received rescue therapy before day 29; all had the CFH Y402H CC “high-risk” genotype for AMD. Nine patients completed the study without rescue with improvements from baseline in best-corrected visual acuity (8 Early Treatment Diabetic Retinopathy Study letters), central retinal lesion thickness (−50.94 µm), and central retinal thickness (−50.28 µm). There was a trend for association between the CFH Y402H T allele (“low risk” for AMD, n = 6) and improvement.

Conclusions and Relevance  Oral pazopanib (15 mg daily) was well tolerated and resulted in improvements in mean best-corrected visual acuity, central retinal lesion thickness, and central retinal thickness at day 29 in a per-protocol, nonrescued AMD population (n = 9). It is postulated that CFH Y402H genotype may help predict which patients respond to pazopanib. The size and length limitations of this study warrant further investigation to determine if oral pazopanib may be an appropriate treatment for a subset of neovascular patients with AMD or as an adjunct to standard of care.

Trial Registration  clinicaltrials.gov Identifier: NCT01051700 and NCT01154062

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

First Page Preview

View Large
First page PDF preview

Figures

Place holder to copy figure label and caption
Figure 1.
Study MD1114555 Patient Disposition

One patient in the per-protocol (PP) population completed the study but received intravitreal therapy after day 29. LOCF indicates last observation carried forward; and OC, observed cases.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Change From Baseline by CFH Y402H Genotype Following 28 Days of 15 mg of Oral Pazopanib Daily in Patients With Age-Related Macular Degeneration (Last Observation Carried Forward Population)

A, Change from baseline in best-corrected visual acuity (BCVA) at day 29. ETDRS indicates Early Treatment Diabetic Retinopathy Study. B, Change from baseline in central retinal thickness (CRT) at day 29.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Mean Plasma Pazopanib Concentrations by Dose in Healthy Participants and Patients With Age-Related Macular Degeneration

Error bars are 1 SE. Patients with age-related macular degeneration received 15 mg; all other concentrations refer to healthy participants.

Graphic Jump Location

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
brightcove.createExperiences();