Reduction in the Occurrence of Center-Involved Diabetic Macular Edema

Study Overview
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Brief Summary
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The purpose of this study is to determine if ruboxistaurin can help slow the worsening of an eye disease called macular edema in patients with diabetes.

Official Title
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Reduction in the Occurrence of Center-Involved Diabetic Macular Edema

Conditions
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Diabetic Retinopathy

Intervention / Treatment
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* Drug: ruboxistaurin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 or Type 2 diabetes 18 years or older Non-clinically significant diabetic macular edema Mild to moderate diabetic retinopathy in the study eye, vitreous hemorrhage in the study eye Relatively good vision (20/30 or better) Exclusion Criteria: Surgery or laser treatment in the study eye Glaucoma in the study eye Glycosylated hemoglobin (HbA1c) greater than 11%, or systolic blood pressure greater than 170 millimeters of mercury (mmHg) Liver disease, dialysis or renal transplant

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruboxistaurin<br>32 milligrams (mg) once daily (QD) oral for up to 36 months | Drug: ruboxistaurin<br>* 32 mg once daily (QD) oral for up to 36 months<br>* Other names: Arxxant;|
| Placebo Comparator: Placebo<br>QD oral for up to 36 months | Drug: placebo<br>* QD oral for up to 36 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Duration of Definite Center of Macula-involved Diabetic Macular Edema (DME) | Duration of center of macula involvement when primary study outcome (DME involvement in center of macula determined by central grading of stereoscopic fundus photographs) was identified at a visit, participant was considered to have had definite center involvement for a specified length of time between the adjacent visits. Total duration of center involvement was calculated. Mean duration was total duration of center involvement divided by total number of participants. Participant durations were summarized, total number of months of center involvement in both treatment groups were displayed. | 6 Months through 36 Months | 
| Occurrence of Sustained Moderate Visual Loss (SMVL) in a Diabetic Retinopathy (DR) Study Eye | The occurrence of SMVL was defined as ≥15 letter decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) in any DR study eye relative to baseline that is sustained for the last 6 months of participation. ETDRS VA: participant starts at the top of the chart containing 5 letters per row and reads down the chart until reaching a row where a minimum of 3 letters on a line cannot be read. Participant is scored by how many letters could be correctly identified. A higher number of letters correctly identified represents better visual acuity. | Baseline, 36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Visual Acuity by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) Chart at 36 Months | ETDRS VA: participant starts at the top of the chart containing 5 letters per row and reads down the chart until reaching a row where a minimum of 3 letters on a line cannot be read. Participant is scored by how many letters could be correctly identified. A higher number of letters correctly identified represents better visual acuity. Results are reported based on the number of diabetic retinopathy (DR) eyes. | Baseline, 36 Months | 
| First Occurrence of Focal/Grid Photocoagulation | The first occurrence of focal/grid photocoagulation regardless of diabetic macular edema (DME) distance from the center of the macula. | Baseline through 36 Months | 
| Change From Baseline in Contrast Sensitivity by Pelli-Robson | Pelli-Robson chart read from left to right + from top to bottom. Each line has 2 groups, each of 3 letters. Letters in each group have same contrast. Contrast in each successive group is less than the preceding group. Participant reads letters starting with highest contrast, continues until 2 or 3 letters in 1 group are incorrectly named. Scored on key showing all letters at full contrast, gives the log contrast sensitivity corresponding to each group. Score is determined by previous group (last group in which 2 or 3 letters were correctly named). Results reported based on number of DR eyes. | Baseline, 36 Months | 
| Progression of Nonproliferative Diabetic Retinopathy (DR) by Seven-field Stereo Fundus Photography | Participants were classified as having experienced progression or no progression of DR by 36-month visit. Progression of DR=3 steps on ETDRS retinopathy severity person scale for participants with both eyes less than proliferative diabetic retinopathy (PDR) at baseline OR 2 steps on ETDRS retinopathy severity eye scale for participants with 1 eye less than PDR at baseline OR application of panretinal laser therapy. Participants were assigned at baseline to ETDRS retinopathy severity scale for persons or individual eyes; determination of no progression/progression was dependent on the scale. | Baseline through 36 Months | 
| Change From Baseline in Estimated Glomerular Filtration Rate | The Modification of Diet in Renal Disease (MDRD) study formula used for the estimated glomerular filtration rate (eGFR) determination is: eGFR = 170 X (Serum creatinine concentration [mg/deciliter (dL)])-0.999 X (Age [years]) -0.176 X (0.762 if participant is female) X (1.180 if participant is black) X (Serum urea nitrogen concentration [mg/dL])-0.170 X (Serum albumin concentration [grams (g)/dL])+0.318. | Baseline, 36 Months | 
| Change From Baseline at Endpoint in Albumin/Creatinine Ratio |  | 36 Months | 
| Change From Baseline at Endpoint in Visual Function by the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) at 36 Months | 25 vision-targeted questions representing 11 vision-related constructs and a 1-item general health rating question. Measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning and task-oriented domains related to daily visual functioning. Each item is converted to a 0 to 100 scale such that a higher score represents better functioning. | 36 Months | 
| Number of Participants With Adverse Events | Summaries of serious adverse events (SAEs) and all other non-serious adverse events (AEs) are located in the Reported Adverse Event Module. | Baseline through 36 Months |