Extension, Carbidopa-levodopa in Neovascular Age-related Macular Degeneration (AMD)

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.

• carbidopa-levodopa 25-100 mg (Drug), also known as Sinemet: High Dose: daily oral administration 2 tablets TID Intermediate Dose: daily oral administration 1 tablet TID

Primary outcomes

• Change in Best Corrected Visual Acuity by ETDRS Visual Scale Testing [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 12), a maximum of 9 months following a 3 month enrollment in NCT03023059.]: 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.

Secondary outcomes

• Number of Adverse Events Experienced [Monthly for 9 months]: Adverse events elicited by nonspecific questioning
• Change in Central Retinal (Macular) Thickness [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, a maximum of 9 months.]: Central retinal thickness (in microns) is measured by spectral domain-optical coherence tomography. An increase in retinal thickness is associated with disease progression. A negative value represents a decrease in retinal thickness and therefore a positive clinical outcome measure.
• Percent Change in Retinal Fluid From Baseline [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.]: Retinal fluid changes on direct retinal examination on spectral domain - optical coherence tomography. Changes in retinal fluid were compared to baseline values. A negative percentage point represents a decrease in retinal fluid and therefore a positive clinical outcome.

Sex: All, ages: 50 Years to 85 Years

Inclusion Criteria:

1. Completion of Protocol 002.
2. A diagnosis of AMd with choroidal neovascularization (CNV) in 1 eye.
3. Normal or Dry AMD of any grade in the second eye.
4. Age 50-85 years.
5. 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.
6. Informed consent at visit 1, which is also Visit 5 of study 002.

Exclusion criteria:

1. 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;
2. Concurrent use of monoamine oxidase (MAO) inhibitors;
3. Any eye condition, disease, or history of trauma in either eye, which can impair vision, except cataract or cataract surgery;
4. BCVA worse than 20/60 in the better eye;
5. Wet AMD in the second eye;
6. Neurologic conditions which can impair vision;
7. Parkinson's Disease;
8. 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;
9. Significant ECG abnormalities, as judged by the Investigator;
10. Estimated glomerular filtration rate (eGFR) <20 ml/min;
11. Liver enzymes >3 X the upper limit of normal;
12. HbA1C >9.0;
13. Any other significant lab abnormalities, as judged by the Investigator.
14. Women of childbearing potential;
15. Known retinal hemorrhage;
16. Subjects who are not fluent in English.

Participant flow

Outcome results

• Change in Best Corrected Visual Acuity by ETDRS Visual Scale Testing (Primary), Mean, Change in letters (BCVA): High Dose 2.7 +/- 1.8
• Number of Adverse Events Experienced (Secondary), Count of participants, Participants: High Dose 3
• Change in Central Retinal (Macular) Thickness (Secondary), Mean, microns: High Dose -18.0 +/- 17.5
• Percent Change in Retinal Fluid From Baseline (Secondary), Mean, percent change: High Dose -3.8 +/- 24.8

Adverse events

Time frame: 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 12), a maximum of 9 months following a 3 month enrollment in NCT03023059. A total of 9 months.

Other adverse events by term

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

• Study Protocol (PDF, 2017-06-24)

• Robert W Snyder, MD, PhD, Principal investigator, Robert W Snyder