Diabetic Macular Edema
Conditions
Brief summary
This randomized clinical trial will evaluate the effect of tonabersat compared with placebo on central subfield thickness (CST) in eyes with center-involved diabetic macular edema (CI-DME) and good visual acuity.
Detailed description
The primary objective is to assess the effects of tonabersat, an orally administered Connexin43 hemichannel inhibitor, on central subfield thickness (mean change) compared with placebo in eyes with CI-DME and good visual acuity at 6 months. Exploratory objectives will evaluate biomarkers of kidney function for potential benefit. Furthermore, this phase 2 study is being conducted to determine whether the conduct of a phase 3 trial has merit and provide information on outcome measures needed to design a phase 3 trial.
Interventions
DRUGTonabersat
Two pills of Study Drug (80 mg tonabersat) is taken orally once daily. It is recommended the Study Drug be taken at bedtime. The first dose (two pills) will be taken at bedtime on the day the participant is randomized.
OTHERPlacebo
Two pills of Study Drug (placebo) is taken orally once daily. It is recommended the Study Drug be taken at bedtime. The first dose (two pills) will be taken at bedtime on the day the participant is randomized.
Sponsors
National Institutes of Health (NIH)
National Eye Institute (NEI)
Juvenile Diabetes Research Foundation
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double-masked, placebo-controlled clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria 1. Adults with type 1 or 2 diabetes mellitus 2. At least one eye with: * Best corrected E-ETDRS visual acuity letter score ≥ 74 (i.e., 20/32 or better) * Ophthalmoscopic evidence of center-involved DME in study eye confirmed by central subfield thickness on spectral domain OCT * Zeiss Cirrus: ≥ 290 µm in females, ≥ 305 µm in males * Heidelberg Spectralis: ≥ 305 µm in females, ≥ 320 µm in males * Recruitment will be monitored with a goal to have equal proportions in the following categories above the CI-DME thresholds: \<75 μm, 75 μm to \<175 μm, ≥175 μm 3. Media clarity, pupillary dilation, and study participant cooperation sufficient for adequate OCT Key
Exclusion criteria
* Macular edema is considered to be due to a cause other than DME * Major ocular surgery within prior 4 months, or anticipated after randomization * History of focal/grid laser or other ocular surgical, intravitreal, or peribulbar treatment for DR or DME within prior 1 year, and no more than 4 anti-VEGF injections within prior 3 years * Anticipated need to treat DME or DR during the first 6 months, or anticipated need for cataract surgery during study period * Any history of vitrectomy * Systemic anti-VEGF or pro-VEGF treatment within 12 months prior to randomization * History of chronic renal failure requiring dialysis or kidney transplant * History of moderate to severe hepatic impairment, including known liver function test (LFT) values \> 3x's the upper limit of normal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean change in central subfield thickness | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change in retinal volume from baseline | 6 months | — |
| Percentage of eyes central subfield thickness below optical coherence machine- and sex-specific threshold for DME and at least a 10% decrease from baseline | 6 months | Composite outcome, gender-specific spectral domain optical coherence tomography equivalent of 250 µm on Zeiss Stratus optical coherence tomography |
| Mean change in visual acuity from baseline | 6 months | — |
| Percentage of eyes receiving other treatment for DME prior to the 6 month visit | 6 months | — |
Countries
United States
Outcome results
None listed