Dose Ranging Study of Carbidopa-levodopa

NCT03023059 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 0002
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

From 3 large patient databases, patients diagnosed with AMD who have never taken levodopa(L-DOPA) containing medications have a mean age of diagnosis at 71 years. Patients who have been treated with L-DOPA containing medications have a mean age of diagnosis of AMD at 79 years. L-DOPA binds to GPR143 in the retinal pigment epithelium, and releases PEDF, which protects the retina and downregulates VEGF, which is the cause of neovascularization. The Investigators will evaluate the safety and tolerability of carbidopa-levodopa in patients with Neovascular AMD, and measure the effects on visual acuity and retinal abnormalities due to "wet" (neovascular) AMD. The Investigators will evaluate the safety and tolerability of carbidopa-levodopa in patients with Neovascular AMD who are already on treatment with anti-VEGF intraocular injections, and measure the effects on visual acuity, retinal abnormalities due to "wet" AMD, and document the number of anti-VEGF injections required during the study.

Conditions

Age-related Macular Degeneration

Keywords

L-DOPA; GPR143; PEDF; VEGF

Outcome Measures

Primary Outcomes (1)

• Change in Best Corrected Visual Acuity by Early Treatment Diabetic Retinopathy Study Chart Visual Scale Testing

  This outcome is a measure of letters correctly identified using an Early Treatment Diabetic Retinopathy Study chart. The higher the number of letters identified, the better the participant's visual acuity.

  From the start of the study to the end (up to 120 days).

Secondary Outcomes (3)

• Change in Central Retinal (Macular) Thickness

  From the start of the study to the end (up to 120 days).

• Percent Change in Retinal Fluid From Baseline

  From the start of the study to the commonly used timeframe of 6 months (~192 days), given that fluid was assessed at 6 months from baseline as commonly evaluated in studies involving AMD.

• Treatment Emergent Adverse Events

  From the start of the study to the commonly used timeframe of 6 months (~192 days), given that fluid was assessed at 6 months, we opted to include the evaluation of adverse events within the six months.

Study Arms (1)

Escalating dose of carbidopa-levodopa

EXPERIMENTAL

The intervention is that patients will receive open label, commercially available Carbidopa-Levodopa 25 Mg-100 Mg oral tablet, once daily hs for one month, followed by one tablet dosed three times daily, in the morning, with supper and hs for one month, followed by two tablets dosed three times daily, in the morning, with supper and hs for one month (100-600 mg of levodopa daily). This is the equivalent of very low to moderate doses of carbidopa-levodopa in patients with Parkinson's disease (daily dose of levodopa 200-800 mg).

Drug: Carbidopa-Levodopa, 25 Mg-100 Mg Oral Tablet

Interventions

Carbidopa-Levodopa, 25 Mg-100 Mg Oral Tablet DRUG

See Arm description

Also known as: Sinemet

Escalating dose of carbidopa-levodopa

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of AMD with choroidal neovascularization (CNV) in one eye;
• a. Not previously treated with anti-VEGF injections; or
• b. On anti-VEGF injections for at least 3 months, and meets criteria for a repeat injection; or
• c. Patients, who have completed Study 001, may enter this trial at the point of initiation of the month of treatment with the dose of carbidopa-levodopa, that they received in Study 001;
• Normal or dry AMD of any grade in the second eye;
• Willingness to maintain AREDS vitamin supplements throughout the study, or remain off these supplements for the duration of the study, if not taking them prior to the study;
• Informed Consent at Baseline.

You may not qualify if:

• Any current use of L-DOPA containing medication or dopamine agonist medication, or any planned use of any of these agents, except for study medication, during the study;
• Concurrent use of monoamine oxidase (MAO) inhibitors;
• Any eye condition, disease, or history of trauma in either eye, which can impair vision, except cataract or cataract surgery;
• Best Corrected Visual Acuity (BCVA) worse than 20/60 in the better eye;
• Wet AMD in the second eye;
• Neurologic conditions which can impair vision;
• Parkinson's Disease;
• Significant orthostatic hypotension, defined as a drop in systolic blood pressure, immediately upon changing from the supine to standing position, of \>19 mmHg, or a symptomatic drop in systolic blood pressure, immediately upon changing from the supine to standing position;
• Significant ECG abnormalities, as judged by the Investigator;
• Estimated glomerular filtration rate (eGFR) \<20 ml/min;
• Liver enzymes \>3 X the upper limit of normal;
• HbA1C \>9.0;
• Any other significant lab abnormalities, as judged by the Investigator;
• Women of childbearing potential;
• Known retinal hemorrhage;

Sponsors & Collaborators

• Snyder, Robert W., M.D., Ph.D., P.C.: lead

Study Sites (1)

Robert W Snyder, MD, PhD, PC

Tucson, Arizona, 85712, United States

Location

Related Publications (10)

• Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004 Nov;82(11):844-51. Epub 2004 Dec 14.

  PMID: 15640920 BACKGROUND

• Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med. 2008 Jun 12;358(24):2606-17. doi: 10.1056/NEJMra0801537. No abstract available.

  PMID: 18550876 BACKGROUND

• Bressler SB, Munoz B, Solomon SD, West SK; Salisbury Eye Evaluation (SEE) Study Team. Racial differences in the prevalence of age-related macular degeneration: the Salisbury Eye Evaluation (SEE) Project. Arch Ophthalmol. 2008 Feb;126(2):241-5. doi: 10.1001/archophthalmol.2007.53.

  PMID: 18268216 BACKGROUND

• Ferrara N. Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy. Nat Med. 2010 Oct;16(10):1107-11. doi: 10.1038/nm1010-1107. No abstract available.

  PMID: 20930754 BACKGROUND

• Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS. L-DOPA is an endogenous ligand for OA1. PLoS Biol. 2008 Sep 30;6(9):e236. doi: 10.1371/journal.pbio.0060236.

  PMID: 18828673 BACKGROUND

• Falk T, Congrove NR, Zhang S, McCourt AD, Sherman SJ, McKay BS. PEDF and VEGF-A output from human retinal pigment epithelial cells grown on novel microcarriers. J Biomed Biotechnol. 2012;2012:278932. doi: 10.1155/2012/278932. Epub 2012 Apr 2.

  PMID: 22547925 BACKGROUND

• Brilliant MH, Vaziri K, Connor TB Jr, Schwartz SG, Carroll JJ, McCarty CA, Schrodi SJ, Hebbring SJ, Kishor KS, Flynn HW Jr, Moshfeghi AA, Moshfeghi DM, Fini ME, McKay BS. Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration. Am J Med. 2016 Mar;129(3):292-8. doi: 10.1016/j.amjmed.2015.10.015. Epub 2015 Oct 30.

  PMID: 26524704 BACKGROUND

• Westfall TC, Westfall DP. Neurotransmission: The Autonomic and Somatic Nervous Systems. Pharmacological Basis of Therapeutics, 12th Edition, 171-218, McGraw-Hill, 2011.

  BACKGROUND

• Standaert DG, Roberson ED. Treatment of Central Nervous System Degenerative Disorders. Pharmacological Basis of Therapeutics, 12th Edition, 609-628, McGraw-Hill, 2011

  BACKGROUND

• Lim JH, Wickremasinghe SS, Xie J, Chauhan DS, Baird PN, Robman LD, Hageman G, Guymer RH. Delay to treatment and visual outcomes in patients treated with anti-vascular endothelial growth factor for age-related macular degeneration. Am J Ophthalmol. 2012 Apr;153(4):678-86, 686.e1-2. doi: 10.1016/j.ajo.2011.09.013. Epub 2012 Jan 14.

  PMID: 22245460 BACKGROUND

MeSH Terms

Conditions

Macular Degeneration

Interventions

carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Limitations and Caveats

The major limitations of our study include the small sample size and limited patient racial diversity.

Results Point of Contact

• Title: Dr. Robert W. Snyder
• Organization: Robert W Snyder, MD, PhD, PC

rsnyder781@gmail.com

5206616516

Study Officials

• Robert W Snyder, MD, PhD

  Robert W Snyder, MD, PhD, PC

  PRINCIPAL INVESTIGATOR

• Timothy C Fagan, MD

  Robert W Snyder, MD, PhD, PC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2017
• First Posted: January 18, 2017
• Study Start: May 2, 2017
• Primary Completion: March 18, 2020
• Study Completion: May 4, 2020
• Last Updated: September 12, 2025
• Results First Posted: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)