Clincosm LogoSign in Get a demo

Effect of Ruboxistaurin on Clinically Significant Macular Edema

Sponsor
Chromaderm, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00133952
Collaborator
(none)
309
Enrollment
41
Locations
2
Arms
71
Duration (Months)
7.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
309 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
The Effect of Ruboxistaurin on Vision Loss in Patients With Diabetes Mellitus and Clinically Significant Macular Edema
Study Start Date :
Aug 1, 2005
Actual Primary Completion Date :
Jul 1, 2011
Actual Study Completion Date :
Jul 1, 2011

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Sustained Moderate Visual Loss (SMVL) Any Time Baseline Through Month 48 [Baseline through 48 months]

      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).

    Secondary Outcome Measures

    1. Change From Baseline to Month 24 in Mean Retinal Thickness Within 500 Microns of the Center of the Macula [Baseline, 24 months]

      Least Squares (LS) Mean values were controlled for treatment, pooled center, and baseline value.

    2. Number of Eyes With Significant Center-Involved Macular Edema at Any Time From Baseline Through Month 24 [Baseline through 24 months]

      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).

    3. Time to Focal Photocoagulation [Baseline through 48 months]

    4. Change From Baseline to Month 24 in Contrast Sensitivity [Baseline, 24 months]

      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.

    5. Change From Baseline to Month 24 in Retinal Thickness at the Center of the Macula [Baseline, up to 24 months]

    6. Number of Participants Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 [Baseline through 24 months]

    7. Number of Participants Not Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 [Baseline through 24 months]

    8. Number of Participants Requiring Repeat Focal Photocoagulation at Any Time From Baseline Though Month 24 [Baseline through 24 months]

      Repeat focal photocoagulation is defined as 2 or more focal photocoagulation treatments needed during the study.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 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. Phoenix Arizona United States 85020
    2 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. Artesia California United States 90701
    3 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. Newark Delaware United States 19713
    4 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. Jacksonville Florida United States 32204
    5 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. Augusta Georgia United States 30909
    6 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. Indianapolis Indiana United States 46280
    7 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. Baltimore Maryland United States 21287
    8 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. Boston Massachusetts United States 02215
    9 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. Grand Rapids Michigan United States 49525
    10 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. Portsmouth New Hampshire United States 03801
    11 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. Slingerlands New York United States 12159
    12 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. Asheville North Carolina United States 28803
    13 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. Lakewood Ohio United States 44107
    14 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. Kingston Pennsylvania United States 18704
    15 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
    16 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
    17 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. Dallas Texas United States 75231
    18 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
    19 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
    20 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. Halifax Nova Scotia Canada B3H 2Y9
    21 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. London Ontario Canada N6A 4G5
    22 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. Mississauga Ontario Canada L4W 1W0
    23 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. Aarhus Denmark 8000
    24 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. Glostrup Denmark 2600
    25 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. Bonn Germany 53127
    26 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. Leipzig Germany 04103
    27 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. Münster Germany 48145
    28 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. Ulm Germany 89075
    29 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. Kaunas Lithuania LT-50009
    30 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. Mexico City Mexico 6700
    31 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. Monterrey Mexico 64710
    32 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 Luis Potosi Mexico 78395
    33 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. Coimbra Portugal 3000-548
    34 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. Lisbon Portugal 1150-199
    35 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. Porto Portugal 4202-451
    36 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. Bucharest Romania 050098
    37 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. Alicante Spain 03016
    38 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. Barcelona Spain 08022
    39 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. Valladolid Spain 47071
    40 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. London Greater London United Kingdom SE5 9RS
    41 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. London United Kingdom EC1V 2PD

    Sponsors and Collaborators

    • Chromaderm, Inc.

    Investigators

    • Study Director: Karl Beutner, Chromaderm, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Chromaderm, Inc.
    ClinicalTrials.gov Identifier:
    NCT00133952
    Other Study ID Numbers:
    • 5882
    • B7A-MC-MBCU
    First Posted:
    Aug 24, 2005
    Last Update Posted:
    Oct 6, 2016
    Last Verified:
    Aug 1, 2016
    Additional relevant MeSH terms:
    Macular Edema
    Edema
    Ruboxistaurin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Period Title: Overall Study
    STARTED 157 152
    Received at Least One Dose of Study Drug 153 149
    COMPLETED 115 124
    NOT COMPLETED 42 28

    Baseline Characteristics

    Arm/Group Title Placebo Ruboxistaurin Total
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months Total of all reporting groups
    Overall Participants 157 152 309
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.5
    (9.3)
    55.4
    (9.9)
    55.5
    (9.6)
    Sex: Female, Male (Count of Participants)
    Female
    67
    42.7%
    66
    43.4%
    133
    43%
    Male
    90
    57.3%
    86
    56.6%
    176
    57%
    Race/Ethnicity, Customized (participants) [Number]
    Caucasian
    117
    74.5%
    111
    73%
    228
    73.8%
    African Descent
    18
    11.5%
    15
    9.9%
    33
    10.7%
    East Asian
    2
    1.3%
    3
    2%
    5
    1.6%
    West Asian
    0
    0%
    2
    1.3%
    2
    0.6%
    Hispanic
    20
    12.7%
    21
    13.8%
    41
    13.3%
    Region of Enrollment (participants) [Number]
    United States
    52
    33.1%
    46
    30.3%
    98
    31.7%
    Portugal
    16
    10.2%
    17
    11.2%
    33
    10.7%
    Mexico
    7
    4.5%
    10
    6.6%
    17
    5.5%
    Canada
    11
    7%
    11
    7.2%
    22
    7.1%
    Spain
    9
    5.7%
    9
    5.9%
    18
    5.8%
    Lithuania
    1
    0.6%
    0
    0%
    1
    0.3%
    Romania
    13
    8.3%
    12
    7.9%
    25
    8.1%
    Denmark
    26
    16.6%
    26
    17.1%
    52
    16.8%
    Germany
    13
    8.3%
    10
    6.6%
    23
    7.4%
    United Kingdom
    5
    3.2%
    5
    3.3%
    10
    3.2%
    France
    4
    2.5%
    6
    3.9%
    10
    3.2%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Sustained Moderate Visual Loss (SMVL) Any Time Baseline Through Month 48
    Description 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).
    Time Frame Baseline through 48 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who took at least 1 dose of study drug and had post-baseline SMVL measurements.
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Measure Participants 146 138
    Number [percent of participants]
    3.4
    2.2%
    2.2
    1.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Ruboxistaurin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.724
    Comments
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.63
    Confidence Interval (2-Sided) 95%
    0.15 to 2.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline to Month 24 in Mean Retinal Thickness Within 500 Microns of the Center of the Macula
    Description Least Squares (LS) Mean values were controlled for treatment, pooled center, and baseline value.
    Time Frame Baseline, 24 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who took at least 1 dose of study drug and had both baseline and post-baseline retinal thickness measurements.
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Measure Participants 148 149
    Least Squares Mean (Standard Error) [micrometer (µm)]
    12.8
    (5.5)
    9.4
    (5.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Ruboxistaurin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.616
    Comments
    Method Mixed models repeated measures
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value -3.3
    Confidence Interval (2-Sided) 95%
    -16.5 to 9.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Number of Eyes With Significant Center-Involved Macular Edema at Any Time From Baseline Through Month 24
    Description 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).
    Time Frame Baseline through 24 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who took at least 1 dose of study drug and had post-baseline macular edema measurements.
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Measure Participants 148 149
    Measure Eyes 286 286
    Number [Eyes]
    77
    76
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Ruboxistaurin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.971
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.99
    Confidence Interval (2-Sided) 95%
    0.68 to 1.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Time to Focal Photocoagulation
    Description
    Time Frame Baseline through 48 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who took at least 1 dose of study drug and had post-baseline determination of focal photocoagulation treatment.
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Measure Participants 148 149
    Median (95% Confidence Interval) [months]
    NA
    NA
    5. Secondary Outcome
    Title Change From Baseline to Month 24 in Contrast Sensitivity
    Description 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.
    Time Frame Baseline, 24 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who took at least 1 dose of study drug and had both baseline and post-baseline contrast sensitivity measurements.
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Measure Participants 148 149
    Least Squares Mean (Standard Error) [letters read correctly]
    -1.1
    (0.4)
    -0.6
    (0.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Ruboxistaurin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.344
    Comments
    Method Mixed models repeated measures
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -0.6 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline to Month 24 in Retinal Thickness at the Center of the Macula
    Description
    Time Frame Baseline, up to 24 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who took at least 1 dose of study drug and had both baseline and post-baseline retinal thickness measurements, last observation carried forward (LOCF).
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Measure Participants 148 149
    Mean (Standard Deviation) [micrometer (µm)]
    10.5
    (65.4)
    13.1
    (74.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Ruboxistaurin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.663
    Comments
    Method ANCOVA
    Comments
    7. Secondary Outcome
    Title Number of Participants Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24
    Description
    Time Frame Baseline through 24 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who took at least 1 dose of study drug and had post-baseline determination of focal photocoagulation treatment.
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Measure Participants 148 149
    Number [participants]
    35
    22.3%
    26
    17.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Ruboxistaurin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.203
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.68
    Confidence Interval (2-Sided) 95%
    0.37 to 1.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Number of Participants Not Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24
    Description
    Time Frame Baseline through 24 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who took at least 1 dose of study drug and had post-baseline determination of focal photocoagulation treatment.
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Measure Participants 148 149
    Number [participants]
    113
    72%
    123
    80.9%
    9. Secondary Outcome
    Title Number of Participants Requiring Repeat Focal Photocoagulation at Any Time From Baseline Though Month 24
    Description Repeat focal photocoagulation is defined as 2 or more focal photocoagulation treatments needed during the study.
    Time Frame Baseline through 24 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who took at least 1 dose of study drug and had post-baseline determination of focal photocoagulation treatment.
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    Measure Participants 148 149
    Number [participants]
    11
    7%
    12
    7.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.749
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.16
    Confidence Interval (2-Sided) 95%
    0.46 to 2.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Placebo Ruboxistaurin
    Arm/Group Description Taken orally daily for up to 48 months 32 milligrams (mg) taken orally daily for up to 48 months
    All Cause Mortality
    Placebo Ruboxistaurin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Ruboxistaurin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 31/153 (20.3%) 36/149 (24.2%)
    Blood and lymphatic system disorders
    Anaemia 0/153 (0%) 0 3/149 (2%) 3
    Thrombocytopenia 1/153 (0.7%) 1 0/149 (0%) 0
    Cardiac disorders
    Angina pectoris 1/153 (0.7%) 1 1/149 (0.7%) 1
    Arteriosclerosis coronary artery 0/153 (0%) 0 1/149 (0.7%) 4
    Atrial fibrillation 0/153 (0%) 0 1/149 (0.7%) 1
    Cardiac failure 0/153 (0%) 0 1/149 (0.7%) 2
    Cardio-respiratory arrest 1/153 (0.7%) 1 0/149 (0%) 0
    Coronary artery disease 3/153 (2%) 3 1/149 (0.7%) 1
    Myocardial infarction 2/153 (1.3%) 2 1/149 (0.7%) 1
    Myocardial ischaemia 1/153 (0.7%) 1 1/149 (0.7%) 1
    Nodal arrhythmia 0/153 (0%) 0 1/149 (0.7%) 1
    Pericarditis 0/153 (0%) 0 1/149 (0.7%) 1
    Ear and labyrinth disorders
    Deafness unilateral 0/153 (0%) 0 1/149 (0.7%) 1
    Gastrointestinal disorders
    Constipation 0/153 (0%) 0 1/149 (0.7%) 1
    Erosive oesophagitis 0/153 (0%) 0 1/149 (0.7%) 1
    General disorders
    Pyrexia 1/153 (0.7%) 1 0/149 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 1/153 (0.7%) 1 0/149 (0%) 0
    Hepatic function abnormal 1/153 (0.7%) 1 0/149 (0%) 0
    Immune system disorders
    Hypersensitivity 1/153 (0.7%) 1 0/149 (0%) 0
    Infections and infestations
    Abscess 0/153 (0%) 0 1/149 (0.7%) 2
    Abscess limb 1/153 (0.7%) 1 0/149 (0%) 0
    Appendicitis 1/153 (0.7%) 1 1/149 (0.7%) 1
    Cellulitis 1/153 (0.7%) 1 0/149 (0%) 0
    Erysipelas 1/153 (0.7%) 1 1/149 (0.7%) 1
    Gangrene 1/153 (0.7%) 1 0/149 (0%) 0
    Gastroenteritis 0/153 (0%) 0 1/149 (0.7%) 1
    Influenza 0/153 (0%) 0 1/149 (0.7%) 1
    Localised infection 2/153 (1.3%) 2 0/149 (0%) 0
    Omphalitis 0/153 (0%) 0 1/149 (0.7%) 1
    Pilonidal cyst 1/153 (0.7%) 1 0/149 (0%) 0
    Pneumonia 3/153 (2%) 3 5/149 (3.4%) 5
    Pneumonia viral 0/153 (0%) 0 1/149 (0.7%) 1
    Pulmonary tuberculosis 1/153 (0.7%) 1 0/149 (0%) 0
    Pyelonephritis 1/153 (0.7%) 1 0/149 (0%) 0
    Sepsis 1/153 (0.7%) 1 1/149 (0.7%) 1
    Soft tissue infection 1/153 (0.7%) 1 0/149 (0%) 0
    Urinary tract infection 1/153 (0.7%) 1 1/149 (0.7%) 4
    Wound infection 2/153 (1.3%) 3 0/149 (0%) 0
    Injury, poisoning and procedural complications
    Concussion 1/153 (0.7%) 1 0/149 (0%) 0
    Fall 1/153 (0.7%) 1 2/149 (1.3%) 2
    Femur fracture 0/153 (0%) 0 1/149 (0.7%) 1
    Hip fracture 0/153 (0%) 0 1/149 (0.7%) 1
    Humerus fracture 0/153 (0%) 0 1/149 (0.7%) 1
    Lumbar vertebral fracture 1/153 (0.7%) 1 0/149 (0%) 0
    Muscle rupture 1/153 (0.7%) 1 0/149 (0%) 0
    Patella fracture 1/153 (0.7%) 1 0/149 (0%) 0
    Radius fracture 1/153 (0.7%) 1 0/149 (0%) 0
    Tendon rupture 1/153 (0.7%) 1 0/149 (0%) 0
    Thoracic vertebral fracture 0/153 (0%) 0 1/149 (0.7%) 1
    Vascular pseudoaneurysm 1/153 (0.7%) 1 0/149 (0%) 0
    Investigations
    Hiv test positive 0/153 (0%) 0 1/149 (0.7%) 1
    Weight decreased 1/153 (0.7%) 1 0/149 (0%) 0
    Metabolism and nutrition disorders
    Diabetes mellitus inadequate control 0/153 (0%) 0 3/149 (2%) 4
    Diabetic foot 0/153 (0%) 0 1/149 (0.7%) 2
    Diabetic ketoacidosis 0/153 (0%) 0 3/149 (2%) 3
    Hyperglycaemia 0/153 (0%) 0 1/149 (0.7%) 1
    Hyperkalaemia 0/153 (0%) 0 1/149 (0.7%) 1
    Hypoglycaemia 0/153 (0%) 0 1/149 (0.7%) 1
    Musculoskeletal and connective tissue disorders
    Flank pain 1/153 (0.7%) 1 0/149 (0%) 0
    Musculoskeletal chest pain 0/153 (0%) 0 1/149 (0.7%) 1
    Osteoarthritis 1/153 (0.7%) 2 0/149 (0%) 0
    Pseudarthrosis 0/153 (0%) 0 1/149 (0.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder papilloma 0/153 (0%) 0 1/149 (0.7%) 1
    Breast cancer metastatic 1/153 (0.7%) 1 0/149 (0%) 0
    Colon adenoma 0/153 (0%) 0 1/149 (0.7%) 1
    Colon cancer 2/153 (1.3%) 2 1/149 (0.7%) 1
    Haemangioma 0/153 (0%) 0 1/149 (0.7%) 1
    Malignant melanoma 0/153 (0%) 0 1/149 (0.7%) 1
    Multiple myeloma 0/153 (0%) 0 1/149 (0.7%) 1
    Nervous system disorders
    Cerebral infarction 1/153 (0.7%) 1 0/149 (0%) 0
    Cerebrovascular accident 1/153 (0.7%) 1 1/149 (0.7%) 1
    Viith nerve paralysis 0/153 (0%) 0 1/149 (0.7%) 1
    Psychiatric disorders
    Depression 1/153 (0.7%) 1 0/149 (0%) 0
    Renal and urinary disorders
    Diabetic nephropathy 1/153 (0.7%) 1 0/149 (0%) 0
    Haematuria 0/153 (0%) 0 2/149 (1.3%) 6
    Renal failure 0/153 (0%) 0 3/149 (2%) 3
    Renal failure acute 2/153 (1.3%) 2 1/149 (0.7%) 1
    Renal failure chronic 0/153 (0%) 0 1/149 (0.7%) 1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/153 (0%) 0 1/149 (0.7%) 1
    Prostatitis 0/153 (0%) 0 1/149 (0.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 0/153 (0%) 0 1/149 (0.7%) 1
    Acute respiratory failure 1/153 (0.7%) 1 0/149 (0%) 0
    Chronic obstructive pulmonary disease 1/153 (0.7%) 1 0/149 (0%) 0
    Dyspnoea 0/153 (0%) 0 1/149 (0.7%) 1
    Pulmonary embolism 0/153 (0%) 0 1/149 (0.7%) 1
    Pulmonary hypertension 0/153 (0%) 0 1/149 (0.7%) 1
    Pulmonary oedema 0/153 (0%) 0 1/149 (0.7%) 1
    Respiratory failure 1/153 (0.7%) 1 1/149 (0.7%) 1
    Vascular disorders
    Haemorrhage 1/153 (0.7%) 1 0/149 (0%) 0
    Hypertension 0/153 (0%) 0 1/149 (0.7%) 1
    Hypotension 0/153 (0%) 0 1/149 (0.7%) 1
    Thrombosis 1/153 (0.7%) 1 0/149 (0%) 0
    Other (Not Including Serious) Adverse Events
    Placebo Ruboxistaurin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 112/153 (73.2%) 118/149 (79.2%)
    Eye disorders
    Cataract 6/153 (3.9%) 7 5/149 (3.4%) 10
    Lacrimation increased 5/153 (3.3%) 6 0/149 (0%) 0
    Vision blurred 5/153 (3.3%) 6 5/149 (3.4%) 5
    Gastrointestinal disorders
    Diarrhoea 8/153 (5.2%) 11 13/149 (8.7%) 15
    Nausea 7/153 (4.6%) 7 5/149 (3.4%) 5
    Vomiting 5/153 (3.3%) 6 6/149 (4%) 7
    General disorders
    Pyrexia 7/153 (4.6%) 10 6/149 (4%) 9
    Infections and infestations
    Bronchitis 5/153 (3.3%) 5 4/149 (2.7%) 4
    Influenza 14/153 (9.2%) 20 7/149 (4.7%) 7
    Localised infection 7/153 (4.6%) 8 0/149 (0%) 0
    Nasopharyngitis 8/153 (5.2%) 10 13/149 (8.7%) 20
    Upper respiratory tract infection 3/153 (2%) 3 5/149 (3.4%) 5
    Injury, poisoning and procedural complications
    Fall 5/153 (3.3%) 5 3/149 (2%) 4
    Metabolism and nutrition disorders
    Hypercholesterolaemia 11/153 (7.2%) 11 4/149 (2.7%) 5
    Hypoglycaemia 5/153 (3.3%) 7 0/149 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 5/153 (3.3%) 5 7/149 (4.7%) 10
    Back pain 5/153 (3.3%) 6 10/149 (6.7%) 11
    Pain in extremity 5/153 (3.3%) 5 3/149 (2%) 4
    Nervous system disorders
    Dizziness 5/153 (3.3%) 7 3/149 (2%) 3
    Headache 13/153 (8.5%) 17 14/149 (9.4%) 17
    Neuropathy peripheral 5/153 (3.3%) 5 1/149 (0.7%) 1
    Psychiatric disorders
    Depression 2/153 (1.3%) 2 5/149 (3.4%) 5
    Respiratory, thoracic and mediastinal disorders
    Cough 3/153 (2%) 3 8/149 (5.4%) 8
    Vascular disorders
    Hypertension 14/153 (9.2%) 15 13/149 (8.7%) 13

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title info@chroma-derm.com
    Organization Chromaderm
    Phone
    Email info@chroma-derm.com
    Responsible Party:
    Chromaderm, Inc.
    ClinicalTrials.gov Identifier:
    NCT00133952
    Other Study ID Numbers:
    • 5882
    • B7A-MC-MBCU
    First Posted:
    Aug 24, 2005
    Last Update Posted:
    Oct 6, 2016
    Last Verified:
    Aug 1, 2016