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Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration.
Ophthalmology 2015; 122(3):579-88O

Abstract

PURPOSE

To evaluate pazopanib eye drops in subjects with active subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

DESIGN

Multicountry, randomized, parallel-group, double-masked, active and placebo-controlled, dose-ranging study of eye drops.

PARTICIPANTS

A total of 510 subjects (93% white; 58% female; mean age, 75.3 years) whose AMD was previously managed by anti-vascular endothelial growth factor intravitreal injections.

METHODS

Treatments administered for 52 weeks included placebo eye drops instilled 4 times daily (n=73); pazopanib 5 mg/ml instilled 3 (n=72) or 4 times daily (n=74); pazopanib 10 mg/ml instilled 2 (n=73), 3 (n=73), or 4 times daily (n=72); or ranibizumab injection administered once every 4 weeks (n=73). In addition, for all eye drop treatment groups, open-label ranibizumab was administered as needed.

MAIN OUTCOME MEASURES

The main outcome measures were best-corrected visual acuity (BCVA) and injection frequency assessed at week 52. Safety was assessed every 4 weeks and pazopanib plasma concentrations were determined at weeks 4 and 24.

RESULTS

At week 52, pazopanib, with allowance for as-needed ranibizumab injections, was noninferior to monthly ranibizumab as well as to as-needed ranibizumab administered with placebo eye drops in maintaining BCVA (estimated BCVA gains of 0.3-1.8 vs. 1.4 vs. 0.2 letters, respectively). Pazopanib treatment did not reduce as-needed ranibizumab injections by ≥50% (prespecified efficacy criterion). At week 52, there were no clinically meaningful changes from baseline in retinal thickness or morphology, CNV size, or lesion characteristics on optical coherence tomography or fluorescein angiography. Complement factor H genotype had no effect on the responses to pazopanib and/or ranibizumab (BCVA, injection rate, or optical coherence tomography/fluorescein angiography changes). Steady-state concentrations of pazopanib in plasma seemed to be reached by week 4. The most common ocular adverse events related to pazopanib and ranibizumab were application site pain (3%) and injection site hemorrhage (1%), respectively. No treatment-related serious adverse events were reported.

CONCLUSIONS

Pazopanib was well tolerated. Daily pazopanib eye drops in neovascular AMD subjects did not result in therapeutic benefit beyond that obtained with ranibizumab alone.

Authors+Show Affiliations

Retina Foundation of the Southwest, Dallas, Texas.Retinal Consultants of Arizona, Phoenix, Arizona.GlaxoSmithKline, King of Prussia, Pennsylvania.GlaxoSmithKline, King of Prussia, Pennsylvania.GlaxoSmithKline, King of Prussia, Pennsylvania.Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin.GlaxoSmithKline, King of Prussia, Pennsylvania. Electronic address: wurzelma@gmail.com.GlaxoSmithKline, King of Prussia, Pennsylvania.GlaxoSmithKline, King of Prussia, Pennsylvania.GlaxoSmithKline, King of Prussia, Pennsylvania.

Pub Type(s)

Clinical Trial, Phase II
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25432081

Citation

Csaky, Karl G., et al. "Clinical Evaluation of Pazopanib Eye Drops Versus Ranibizumab Intravitreal Injections in Subjects With Neovascular Age-related Macular Degeneration." Ophthalmology, vol. 122, no. 3, 2015, pp. 579-88.
Csaky KG, Dugel PU, Pierce AJ, et al. Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration. Ophthalmology. 2015;122(3):579-88.
Csaky, K. G., Dugel, P. U., Pierce, A. J., Fries, M. A., Kelly, D. S., Danis, R. P., ... Trivedi, T. (2015). Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration. Ophthalmology, 122(3), pp. 579-88. doi:10.1016/j.ophtha.2014.09.036.
Csaky KG, et al. Clinical Evaluation of Pazopanib Eye Drops Versus Ranibizumab Intravitreal Injections in Subjects With Neovascular Age-related Macular Degeneration. Ophthalmology. 2015;122(3):579-88. PubMed PMID: 25432081.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration. AU - Csaky,Karl G, AU - Dugel,Pravin U, AU - Pierce,Amy J, AU - Fries,Michael A, AU - Kelly,Deborah S, AU - Danis,Ronald P, AU - Wurzelmann,John I, AU - Xu,Chun-Fang, AU - Hossain,Mohammad, AU - Trivedi,Trupti, Y1 - 2014/11/26/ PY - 2014/04/01/received PY - 2014/09/11/revised PY - 2014/09/29/accepted PY - 2014/11/30/entrez PY - 2014/11/30/pubmed PY - 2015/6/16/medline SP - 579 EP - 88 JF - Ophthalmology JO - Ophthalmology VL - 122 IS - 3 N2 - PURPOSE: To evaluate pazopanib eye drops in subjects with active subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Multicountry, randomized, parallel-group, double-masked, active and placebo-controlled, dose-ranging study of eye drops. PARTICIPANTS: A total of 510 subjects (93% white; 58% female; mean age, 75.3 years) whose AMD was previously managed by anti-vascular endothelial growth factor intravitreal injections. METHODS: Treatments administered for 52 weeks included placebo eye drops instilled 4 times daily (n=73); pazopanib 5 mg/ml instilled 3 (n=72) or 4 times daily (n=74); pazopanib 10 mg/ml instilled 2 (n=73), 3 (n=73), or 4 times daily (n=72); or ranibizumab injection administered once every 4 weeks (n=73). In addition, for all eye drop treatment groups, open-label ranibizumab was administered as needed. MAIN OUTCOME MEASURES: The main outcome measures were best-corrected visual acuity (BCVA) and injection frequency assessed at week 52. Safety was assessed every 4 weeks and pazopanib plasma concentrations were determined at weeks 4 and 24. RESULTS: At week 52, pazopanib, with allowance for as-needed ranibizumab injections, was noninferior to monthly ranibizumab as well as to as-needed ranibizumab administered with placebo eye drops in maintaining BCVA (estimated BCVA gains of 0.3-1.8 vs. 1.4 vs. 0.2 letters, respectively). Pazopanib treatment did not reduce as-needed ranibizumab injections by ≥50% (prespecified efficacy criterion). At week 52, there were no clinically meaningful changes from baseline in retinal thickness or morphology, CNV size, or lesion characteristics on optical coherence tomography or fluorescein angiography. Complement factor H genotype had no effect on the responses to pazopanib and/or ranibizumab (BCVA, injection rate, or optical coherence tomography/fluorescein angiography changes). Steady-state concentrations of pazopanib in plasma seemed to be reached by week 4. The most common ocular adverse events related to pazopanib and ranibizumab were application site pain (3%) and injection site hemorrhage (1%), respectively. No treatment-related serious adverse events were reported. CONCLUSIONS: Pazopanib was well tolerated. Daily pazopanib eye drops in neovascular AMD subjects did not result in therapeutic benefit beyond that obtained with ranibizumab alone. SN - 1549-4713 UR - https://www.unboundmedicine.com/medline/citation/25432081/Clinical_evaluation_of_pazopanib_eye_drops_versus_ranibizumab_intravitreal_injections_in_subjects_with_neovascular_age_related_macular_degeneration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-6420(14)00942-7 DB - PRIME DP - Unbound Medicine ER -