Extension, Carbidopa-levodopa in Neovascular AMD

Study Overview
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Brief Summary
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This protocol is an extension of protocol 0002, Proof of Concept and Dose Ranging Study of carbidopa-levodopa in Neovascular AMD. that is a 3 month study of escalating doses of carbidopa-levodopa in neovascular AMD. This trial is a 9 month extension for patients who successfully complete protocol 0002 and wish to continue carbidopa-levodopa therapy. It will use the two higher dose regimens of protocol 0002. these will be assigned according to how well the higher dose was tolerated in protocol 0002.

Detailed Description
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This extension will employ the same medications, measurements, guidelines for anti-VEGF injections and safeguards as in protocol 0002. In combination with protocol 0002, it will provide a total of 12 months of therapy with carbidopa-levodopa.

Official Title
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Extension of Protocol 002, Carbidopa-levodopa in Neovascular Extension of Protocol 002, Carbidopa-levodopa in Neovascular AMD

Conditions
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Macula; Degeneration, Retina

Intervention / Treatment
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* Drug: carbidopa-levodopa 25-100 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of Protocol 002. A diagnosis of AMd with choroidal neovascularization (CNV) in 1 eye. Normal or Dry AMD of any grade in the second eye. Age 50-85 years. Willingness to maintain AREDS vitamin Supplements throughout the study, or remain off of these supplements for the duration of the study, if not taking them prior to the study. Informed consent at visit 1, which is also Visit 5 of study 002. Exclusion criteria: 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; 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; Subjects who are not fluent in English.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients who complete 3 months of escalation dose carbidopa-levodopa, will receive 9 additional months of therapy with the highest dose used in protocol 0002, carbidopa-levodopa 25-100 mg 2 tablets TID. If that dose was not well tolerated in study 0002, the patient will receive the intermediate dose, carbidopa-levodopa 25-100 mg, 1 tablet TID.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose<br>carbidopa-levodopa 25-100 mg 2 tablets TID | Drug: carbidopa-levodopa 25-100 mg<br>* High Dose: daily oral administration 2 tablets TID Intermediate Dose: daily oral administration 1 tablet TID<br>|
| Experimental: Intermediate Dose<br>carbidopa-levodopa 25-100 mg 1 tablet TID | Drug: carbidopa-levodopa 25-100 mg<br>* High Dose: daily oral administration 2 tablets TID Intermediate Dose: daily oral administration 1 tablet TID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity by ETDRS visual scale testing | Currently refracted, normal light, lines and letters read on the ETDRS chart | From the start of the study (Visit 1) to the last completed visit, whether due to patient withdrawal, patient death or the completion of the last visit of the study (visit 10), a maximum of 9 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events experienced by participants during the study | Adverse events elicited by nonspecific questioning | Monthly for 9 months | 
| By OCT, central retinal thickness, in the eye with neovascular AMD | Central retinal thickness by OCT | From the start of the study (Visit 1) to the last completed visit, whether due to patient withdrawal, patient death or the completion of the last visit of the study (visit 10), a maximum of 9 months. | 
| By OCT, drusen volume in the eye without neovascular AMD | drusen volume | From the start of the study (Visit 1) to the last completed visit, whether due to patient withdrawal, patient death or the completion of the last visit of the study, (visit 10), a maximum of 9 months. |