Effect of Ruboxistaurin on Clinically Significant Macular Edema

Study Overview
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Brief Summary
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The purpose of the study is to test the hypothesis that oral administration of ruboxistaurin will reduce the occurrence of sustained moderate visual loss (SMVL) in patients with clinically significant macular edema. SMVL is defined as a 15 letter or more decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity that is sustained for the patient's last 6 months of study participation. The SMVL data from this study will be combined with the SMVL data from Study B7A-MC-MBDL for the purpose of comparing ruboxistaurin to placebo.

Official Title
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The Effect of Ruboxistaurin on Vision Loss in Patients With Diabetes Mellitus and Clinically Significant Macular Edema

Conditions
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Diabetic Macular Edema

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 2 diabetes 18 years or older Hemoglobin A1c (HbA1c) less than or equal to 11% Mild to very severe non-proliferative diabetic retinopathy in the study eye Clinically significant macular edema in the study eye not within 100 microns of center of macula Exclusion Criteria: Previous surgery or laser treatment (or need for laser treatment within 3 months) in the study eye Glaucoma in the study eye Unstable cardiovascular disease Major surgery within past 3 months Significantly impaired kidney or liver function, or malignancy requiring chemotherapy or radiation therapy.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruboxistaurin<br>32 mg taken orally daily for up to 48 months | Drug: Ruboxistaurin<br>* Administered orally<br>* Other names: LY333531;|
| Placebo Comparator: Placebo<br>Taken orally daily for up to 48 months | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Moderate Visual Loss (SMVL) Any Time Baseline Through Month 48 | SMVL is defined as a 15 letter or more decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity that is sustained for the participant's last 6 months of study participation. ETDRS visual acuity uses an eye chart with 5 letters per line. The scores range from 0 (no letters read correctly) to 100 (all letters read correctly). | Baseline through 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Month 24 in Mean Retinal Thickness Within 500 Microns of the Center of the Macula | Least Squares (LS) Mean values were controlled for treatment, pooled center, and baseline value. | Baseline, 24 months | 
| Number of Eyes With Significant Center-Involved Macular Edema at Any Time From Baseline Through Month 24 | Significant center-involved macular edema is defined as an absolute retinal thickness at the center of the macula >2 standard deviations above the mean baseline value (where the mean and standard deviation are calculated at baseline from the randomized population of participants with retinal thickness values of ≤ 300 microns in depth). | Baseline through 24 months | 
| Time to Focal Photocoagulation |  | Baseline through 48 months | 
| Change From Baseline to Month 24 in Contrast Sensitivity | Values are presented as changes in the number of letters read correctly on the Pelli-Robson contrast sensitivity chart which consists of 16 triplets (48 letters total) with letters of the same size but decreasing contrast. Least Squares (LS) Mean values were controlled for treatment, pooled center, and baseline value. | Baseline, 24 months | 
| Change From Baseline to Month 24 in Retinal Thickness at the Center of the Macula |  | Baseline, up to 24 months | 
| Number of Participants Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 |  | Baseline through 24 months | 
| Number of Participants Not Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 |  | Baseline through 24 months | 
| Number of Participants Requiring Repeat Focal Photocoagulation at Any Time From Baseline Though Month 24 | Repeat focal photocoagulation is defined as 2 or more focal photocoagulation treatments needed during the study. | Baseline through 24 months |