Protein Kinase C (PKC) Inhibitor-Diabetic Retinopathy Phase 3 Study

Study Overview
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Brief Summary
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This study is to test whether or not 32 milligrams (mg) of ruboxistaurin a day over three years will reduce vision loss associated with diabetic retinopathy.

Official Title
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Phase 3, Multicenter,Parallel,Randomized Dbl-masked,Placebo-controlled Study of the Effects of 32 mg/dy Ruboxistaurin Vision Loss in Patients With Type 1 or Type 2 Diabetes Mellitus and an Early Treatment Diabetic Retinopathy Study Level Between 47A and 53E.

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 mellitus 18 years or older Meet specific requirements for diabetic retinopathy Free of severe or chronically disabling conditions, except diabetes, diabetic retinopathy and diabetic macular edema Hemoglobin A1c (HbA1C) ≤13.0% Exclusion Criteria: History of panretinal photocoagulation for diabetic retinopathy, conditions that might affect the progression of diabetic retinopathy, or unstable angina Investigators, site personnel directly affiliated with the study and their families Presence of eye disorders that may affect the progression of diabetic retinopathy or cause vision loss Presence of medical disorder, cancer, or elevated laboratory measurements that could represent a safety risk during the study Women who are pregnant, breastfeeding, intend to become pregnant, or who are sexually active without using an acceptable method of birth control

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruboxistaurin<br> | Drug: ruboxistaurin<br>* 32-mg tablet, orally, daily, up to 42 months<br>* Other names: LY333531;|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* 1 tablet, orally, daily, up to 42 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Had Sustained Moderate Visual Loss (SMVL) as Defined as a Visual Acuity Loss of ≥15 Letters Measured Twice During a 6-month Period | SMVL is defined as a ≥15-letter decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) that the participant sustained during the last 6 months of study participation (Months 30-36). Participants who discontinued the study early may have had SMVL if there was a 6-month period of ≥15 letters lost in VA ending with the last visit at which VA was assessed. 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). Percentage of participants = (number of participants who had SMVL) / (number of participants who were randomized) * 100. | Baseline through 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Developed Center Involved or Imminently Threatened Diabetic Macular Edema (DME) | DME is the accumulation of extracellular fluid in the retinal tissue of the macular area, which can reduce the ability for fine visual discrimination. Percentage of participants = (number of participants who developed center involved or imminently threatened DME) / (number of participants who had no center involved or imminently threatened DME at baseline) * 100. | Baseline through 36 months | 
| Percentage of Participants Who Experienced the Development of Proliferative Diabetic Retinopathy (PDR) | Percentage of participants = (number of participants who experienced the development of PDR) / (number of participants who were randomized) * 100. | Baseline through 36 months | 
| Change From Baseline up to 36 Months in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) | NEI-VFQ-25 consisted of 25 questions and was used to measure the influence of visual disability and symptoms on general health of participants. The possible total score range for the NEI-VFQ-25 was from 0 (worst possible outcome) to 100 (best possible outcome). | Baseline, up to 36 months | 
| Change From Baseline up to 36 Months in Mental and Physical Components of the Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Questionnaire | SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions. There are 2 component scores, mental component score (MCS) and physical component score (PCS). MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. Both MCS and PCS have scores ranging from 0 to 100 with higher scores indicating better mental or physical health. | Baseline, up to 36 months |