Evaluation of Tonabersat for DME

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2 Evaluation of Tonabersat for Diabetic Macular Edema (Protocol AN)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: Tonabersat
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Adults with type 1 or 2 diabetes mellitus At least one eye with: Best corrected E-ETDRS visual acuity letter score ≥ 79 (i.e., 20/25 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 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 prior anti-VEGF injections total 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

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-masked, placebo-controlled clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* 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.<br>|
| Active Comparator: Tonabersat (80 mg)<br> | Drug: Tonabersat<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in central subfield thickness |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in retinal volume from baseline |  | 6 months | 
| Percentage of eyes central subfield thickness below optical coherence machine- and gender-specific threshold for DME and at least a 10% decrease from baseline | Composite outcome, gender-specific spectral domain optical coherence tomography equivalent of 250 µm on Zeiss Stratus optical coherence tomography | 6 months | 
| Mean change in visual acuity from baseline |  | 6 months | 
| Percentage of eyes receiving other treatment for DME |  | 6 months |