Effect of Ruboxistaurin on Clinically Significant Macular Edema

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Placebo; Drug: Ruboxistaurin

• Study Type: Interventional
• Enrollment (Actual): 309
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
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  • Ontario
    • London, Ontario, Canada, N6A 4G5
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    • Mississauga, Ontario, Canada, L4W 1W0
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• Denmark
  • Aarhus, Denmark, 8000
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  • Glostrup, Denmark, 2600
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• Germany
  • Bonn, Germany, 53127
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  • Leipzig, Germany, 04103
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  • Münster, Germany, 48145
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  • Ulm, Germany, 89075
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• Lithuania
  • Kaunas, Lithuania, LT-50009
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• Mexico
  • Mexico City, Mexico, 6700
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  • Monterrey, Mexico, 64710
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  • San Luis Potosi, Mexico, 78395
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• Portugal
  • Coimbra, Portugal, 3000-548
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  • Lisbon, Portugal, 1150-199
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  • Porto, Portugal, 4202-451
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• Romania
  • Bucharest, Romania, 050098
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• Spain
  • Alicante, Spain, 03016
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  • Barcelona, Spain, 08022
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  • Valladolid, Spain, 47071
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• United Kingdom
  • London, United Kingdom, EC1V 2PD
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  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
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• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
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  • California
    • Artesia, California, United States, 90701
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  • Delaware
    • Newark, Delaware, United States, 19713
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  • Florida
    • Jacksonville, Florida, United States, 32204
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  • Georgia
    • Augusta, Georgia, United States, 30909
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  • Indiana
    • Indianapolis, Indiana, United States, 46280
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  • Maryland
    • Baltimore, Maryland, United States, 21287
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  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • New York
    • Slingerlands, New York, United States, 12159
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  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Ohio
    • Lakewood, Ohio, United States, 44107
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Pennsylvania
    • Kingston, Pennsylvania, United States, 18704
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Pittsburgh, Pennsylvania, United States, 15213
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • West Mifflin, Pennsylvania, United States, 15122
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Texas
    • Dallas, Texas, United States, 75231
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Houston, Texas, United States, 77030
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • San Antonio, Texas, United States, 78229
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ruboxistaurin; 32 mg taken orally daily for up to 48 months	Drug: Ruboxistaurin; Administered orally; Other Names: LY333531
Placebo Comparator: Placebo; Taken orally daily for up to 48 months	Drug: Placebo; Administered orally

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chromaderm, Inc.

Publications and helpful links

General Publications

• Sheetz MJ, Aiello LP, Davis MD, Danis R, Bek T, Cunha-Vaz J, Shahri N, Berg PH; MBDL and MBCU Study Groups. The effect of the oral PKC beta inhibitor ruboxistaurin on vision loss in two phase 3 studies. Invest Ophthalmol Vis Sci. 2013 Mar 11;54(3):1750-7. doi: 10.1167/iovs.12-11055.

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: August 22, 2005
• First Submitted That Met QC Criteria: August 22, 2005
• First Posted (Estimate): August 24, 2005

Study Record Updates

• Last Update Posted (Estimate): October 6, 2016
• Last Update Submitted That Met QC Criteria: August 25, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Ruboxistaurin
• Other Study ID Numbers: 5882; B7A-MC-MBCU (Other Identifier: Eli Lilly and Company)