Macula; Degeneration, Retina
Conditions
Brief summary
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
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.
Interventions
High Dose: daily oral administration 2 tablets TID Intermediate Dose: daily oral administration 1 tablet TID
Sponsors
Snyder Biomedical Corporation
Snyder, Robert W., M.D., Ph.D., P.C.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carbidopa/Levodopa High Dose carbidopa-levodopa 25-100 mg 2 tablets TID
carbidopa-levodopa 25-100 mg: High Dose: daily oral administration 2 tablets TID Intermediate Dose: daily oral administration 1 tablet TID | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Carbidopa/Levodopa High Dose | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 28 Participants | — |
| Age, Categorical Between 18 and 65 years | 2 Participants | — |
| Age, Continuous | 75 years | — |
| Patients naive to anti-VEGF injections at start of study | 15 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 30 participants | — |
| Sex: Female, Male Female | 16 Participants | — |
| Sex: Female, Male Male | 14 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 3 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Change in Best Corrected Visual Acuity by ETDRS 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.
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.
Population: This population includes participants who completed NCT03022318 (naive to anti-VEGF injections at the time of enrollment) and patients who did not complete NCT03022318 but had been exposed to anti-VEGF injections before study initiation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Change in Best Corrected Visual Acuity by ETDRS Visual Scale Testing | 2.7 Change in letters (BCVA) | Standard Error 1.8 |
Secondary
Change in Central Retinal (Macular) Thickness
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.
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, a maximum of 9 months.
Population: This population includes participants who completed NCT03022318 (naive to anti-VEGF injections at the time of enrollment) and patients who did not complete NCT03022318 but had been exposed to anti-VEGF injections before study initiation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Change in Central Retinal (Macular) Thickness | -18.0 microns | Standard Error 17.5 |
Secondary
Number of Adverse Events Experienced
Adverse events elicited by nonspecific questioning
Time frame: Monthly for 9 months
Population: This population includes participants who completed NCT03022318 (naive to anti-VEGF injections at the time of enrollment) and patients who did not complete NCT03022318 but had been exposed to anti-VEGF injections before study initiation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose | Number of Adverse Events Experienced | 3 Participants |
Secondary
Percent Change in Retinal Fluid From Baseline
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.
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 10), a maximum of 9 months.
Population: This population includes participants who completed NCT03022318 (naive to anti-VEGF injections at the time of enrollment) and patients who did not complete NCT03022318 but had been exposed to anti-VEGF injections before study initiation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Percent Change in Retinal Fluid From Baseline | -3.8 percent change | Standard Error 24.8 |