Reduction in the Occurrence of Center-Involved Diabetic Macular Edema

Sponsor
Chromaderm, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00090519
Collaborator
(none)
731
Enrollment
84
Locations
2
Arms
74
Duration (Months)
8.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
731 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Reduction in the Occurrence of Center-Involved Diabetic Macular Edema
Study Start Date :
Feb 1, 2004
Actual Primary Completion Date :
Apr 1, 2010
Actual Study Completion Date :
Apr 1, 2010

Arms and Interventions

ArmIntervention/Treatment
Experimental: Ruboxistaurin

32 milligrams (mg) once daily (QD) oral for up to 36 months

Drug: ruboxistaurin
32 mg once daily (QD) oral for up to 36 months
Other Names:
  • LY333531
  • Arxxant
  • Placebo Comparator: Placebo

    QD oral for up to 36 months

    Drug: placebo
    QD oral for up to 36 months

    Outcome Measures

    Primary Outcome Measures

    1. Mean Duration of Definite Center of Macula-involved Diabetic Macular Edema (DME) [6 Months through 36 Months]

      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.

    2. Occurrence of Sustained Moderate Visual Loss (SMVL) in a Diabetic Retinopathy (DR) Study Eye [Baseline, 36 Months]

      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.

    Secondary Outcome Measures

    1. Change From Baseline in Visual Acuity by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) Chart at 36 Months [Baseline, 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.

    2. First Occurrence of Focal/Grid Photocoagulation [Baseline through 36 Months]

      The first occurrence of focal/grid photocoagulation regardless of diabetic macular edema (DME) distance from the center of the macula.

    3. Change From Baseline in Contrast Sensitivity by Pelli-Robson [Baseline, 36 Months]

      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.

    4. Progression of Nonproliferative Diabetic Retinopathy (DR) by Seven-field Stereo Fundus Photography [Baseline through 36 Months]

      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.

    5. Change From Baseline in Estimated Glomerular Filtration Rate [Baseline, 36 Months]

      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.

    6. Change From Baseline at Endpoint in Albumin/Creatinine Ratio [36 Months]

    7. Change From Baseline at Endpoint in Visual Function by the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) at 36 Months [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.

    8. Number of Participants With Adverse Events [Baseline through 36 Months]

      Summaries of serious adverse events (SAEs) and all other non-serious adverse events (AEs) are located in the Reported Adverse Event Module.

    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 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1For 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.ArtesiaCaliforniaUnited States90701
    2For 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.Palm SpringsCaliforniaUnited States92262
    3For 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.PowayCaliforniaUnited States92064
    4For 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.Walnut CreekCaliforniaUnited States94598
    5For 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.DenverColoradoUnited States80262
    6For 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 LondonConnecticutUnited States06320
    7For 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.JacksonvilleFloridaUnited States32204
    8For 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.SunriseFloridaUnited States33351
    9For 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.AugustaGeorgiaUnited States30909
    10For 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.Idaho FallsIdahoUnited States83404
    11For 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.WheatonIllinoisUnited States60187
    12For 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.Iowa CityIowaUnited States52242
    13For 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.BaltimoreMarylandUnited States21287
    14For 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.BostonMassachusettsUnited States02215
    15For 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.PeabodyMassachusettsUnited States01960
    16For 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 RapidsMichiganUnited States49525
    17For 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.ColumbiaMissouriUnited States65212
    18For 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.IndependenceMissouriUnited States64055
    19For 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 BrunswickNew JerseyUnited States08901
    20For 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.TeaneckNew JerseyUnited States07666
    21For 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.AlbuquerqueNew MexicoUnited States87102
    22For 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.Rockville CenterNew YorkUnited States11570
    23For 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.CharlotteNorth CarolinaUnited States28210
    24For 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.FargoNorth DakotaUnited States58104
    25For 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.BeachwoodOhioUnited States44122
    26For 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.CincinnatiOhioUnited States45242
    27For 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.ClevelandOhioUnited States44195
    28For 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.Oklahoma CityOklahomaUnited States73104
    29For 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.HersheyPennsylvaniaUnited States17033
    30For 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.PittsburghPennsylvaniaUnited States15213
    31For 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.Rapid CitySouth DakotaUnited States57701
    32For 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.ArlingtonTexasUnited States76012
    33For 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.DallasTexasUnited States75231
    34For 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.HoustonTexasUnited States77030
    35For 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.OgdenUtahUnited States84403
    36For 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.Salt Lake CityUtahUnited States84107
    37For 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.ParramattaNew South WalesAustralia2150
    38For 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.SydneyNew South WalesAustralia2000
    39For 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.WestmeadNew South WalesAustralia2145
    40For 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.WoodvilleSouth AustraliaAustralia5011
    41For 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.NedlandsWestern AustraliaAustralia6009
    42For 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.CuritibaBrazil80420-170
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    45For 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.VancouverBritish ColumbiaCanadaV5Z 4E1
    46For 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.HalifaxNova ScotiaCanadaB3H 2Y9
    47For 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.LondonOntarioCanadaN6A 4G5
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    49For 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.TorontoOntarioCanadaM4N 3M5
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    51For 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.AarhusDenmark8000
    52For 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.GlostrupDenmark2600
    53For 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.BordeauxFrance33076
    54For 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.NantesFrance44093
    55For 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.ParisFrance75010
    56For 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.LeipzigGermany04103
    57For 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.MunsterGermany48145
    58For 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.SulzbachGermany66280
    59For 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.UlmGermanyD-89075
    60For 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.ChennaiIndia600006
    61For 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.HyderabaadIndia500034
    62For 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 DelhiIndia110029
    63For 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.MilanoItaly20132
    64For 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.UdineItaly33100
    65For 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 CityMexico04030
    66For 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.AmsterdamNetherlands1081 HV
    67For 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.RotterdamNetherlands3011 BH
    68For 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.BydgoszczPoland85-822
    69For 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.KatowicePoland40-044
    70For 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.LublinPoland20-081
    71For 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.PoznanPoland61-696
    72For 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.CoimbraPortugal3000-548
    73For 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.MoscowRussian Federation117036
    74For 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.Saint PetersburgRussian Federation195176
    75For 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.AlicanteSpain03015
    76For 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.BarcelonaSpain08022
    77For 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.MadridSpain28002
    78For 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.ValladolidSpain47005
    79For 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.Tao-YuanTaiwan333
    80For 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.LiverpoolMerseysideUnited KingdomL7 8XP
    81For 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.AberdeenScotlandUnited KingdomAB25 2ZN
    82For 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.BirminghamWest MidlandsUnited KingdomB9 5SS
    83For 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.BristolUnited KingdomBS1 2LX
    84For 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.LondonUnited KingdomEC1V 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:
    NCT00090519
    Other Study ID Numbers:
    • 8211
    • B7A-MC-MBDL
    First Posted:
    Aug 31, 2004
    Last Update Posted:
    Oct 6, 2016
    Last Verified:
    Aug 1, 2016
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Period Title: Overall Study
    STARTED371360
    COMPLETED298285
    NOT COMPLETED7375

    Baseline Characteristics

    Arm/Group TitleRuboxistaurinPlaceboTotal
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 monthsTotal of all reporting groups
    Overall Participants371360731
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.20
    (10.85)
    55.15
    (11.18)
    55.17
    (11.01)
    Sex: Female, Male (Count of Participants)
    Female
    138
    37.2%
    137
    38.1%
    275
    37.6%
    Male
    233
    62.8%
    223
    61.9%
    456
    62.4%
    Region of Enrollment (participants) [Number]
    United States
    93
    25.1%
    97
    26.9%
    190
    26%
    Portugal
    15
    4%
    16
    4.4%
    31
    4.2%
    Taiwan
    3
    0.8%
    1
    0.3%
    4
    0.5%
    Spain
    13
    3.5%
    11
    3.1%
    24
    3.3%
    Russian Federation
    28
    7.5%
    24
    6.7%
    52
    7.1%
    United Kingdom
    21
    5.7%
    18
    5%
    39
    5.3%
    Italy
    8
    2.2%
    6
    1.7%
    14
    1.9%
    India
    25
    6.7%
    26
    7.2%
    51
    7%
    France
    11
    3%
    10
    2.8%
    21
    2.9%
    Mexico
    22
    5.9%
    22
    6.1%
    44
    6%
    Canada
    22
    5.9%
    25
    6.9%
    47
    6.4%
    Brazil
    13
    3.5%
    16
    4.4%
    29
    4%
    Poland
    20
    5.4%
    16
    4.4%
    36
    4.9%
    Australia
    20
    5.4%
    17
    4.7%
    37
    5.1%
    Denmark
    26
    7%
    28
    7.8%
    54
    7.4%
    Netherlands
    9
    2.4%
    8
    2.2%
    17
    2.3%
    Germany
    22
    5.9%
    19
    5.3%
    41
    5.6%
    Body Mass Index (BMI) (kilograms/square meters (kg/m^2)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms/square meters (kg/m^2)]
    29.90
    (6.09)
    29.82
    (5.89)
    29.86
    (5.99)
    Blood Pressure (millimeters of mercury (mmHg)) [Mean (Standard Deviation) ]
    Systolic Blood Pressure
    132.90
    (15.25)
    133.50
    (15.58)
    133.20
    (5.99)
    Diastolic Blood Pressure
    77.68
    (8.68)
    77.77
    (9.05)
    77.73
    (8.86)
    Glycosylated hemoglobin (HbA1c) (percent glycosylated hemoglobin) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percent glycosylated hemoglobin]
    8.14
    (1.31)
    8.25
    (1.31)
    8.19
    (1.31)
    Diabetes Type (participants) [Number]
    Type 1
    85
    22.9%
    76
    21.1%
    161
    22%
    Type 2
    286
    77.1%
    284
    78.9%
    570
    78%
    Duration of diabetes (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    15.82
    (8.00)
    15.57
    (7.48)
    15.70
    (7.75)
    Insulin use (participants) [Number]
    Yes
    241
    65%
    228
    63.3%
    469
    64.2%
    No
    130
    35%
    132
    36.7%
    262
    35.8%
    Number of diabetic retinopathy (DR) study eyes per participant (participants) [Number]
    Two
    351
    94.6%
    336
    93.3%
    687
    94%
    One
    20
    5.4%
    24
    6.7%
    44
    6%
    Visual Acuity Score (Letters Correct) (Letters read correctly) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Letters read correctly]
    84.12
    (7.93)
    84.27
    (7.70)
    84.19
    (7.81)
    Diabetic Retinopathy (DR) Level (DR study eyes for each level) [Number]
    <47
    465
    421
    886
    47
    250
    272
    522
    53
    7
    3
    10

    Outcome Measures

    1. Primary Outcome
    TitleMean Duration of Definite Center of Macula-involved Diabetic Macular Edema (DME)
    DescriptionDuration 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.
    Time Frame6 Months through 36 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population including all randomized participants analyzed according to the treatment group to which they were originally assigned by random allocation even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants349346
    Mean (Standard Deviation) [months per participant]
    1.72
    (4.95)
    1.69
    (4.41)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ruboxistaurin, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.969
    Comments
    MethodANOVA
    Comments
    Method of EstimationEstimation ParameterMean Difference (Final Values)
    Estimated Value-0.01
    Confidence Interval (2-Sided) 95%
    -0.714 to 0.686
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    TitleChange From Baseline in Visual Acuity by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) Chart at 36 Months
    DescriptionETDRS 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.
    Time FrameBaseline, 36 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population including all randomized participants analyzed according to the treatment group to which they were originally assigned by random allocation even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants371360
    Measure DR study eyes722695
    Baseline (letters correct) (n=722, 695)
    84.12
    (7.93)
    84.27
    (7.70)
    Change from baseline (n=687,670)
    -1.14
    (7.38)
    -2.30
    (9.21)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ruboxistaurin, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.015
    CommentsP-value is for change from baseline.
    MethodANCOVA
    Comments
    Method of EstimationEstimation ParameterMean Difference (Final Values)
    Estimated Value1.09
    Confidence Interval (2-Sided) 95%
    0.21 to 1.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    TitleFirst Occurrence of Focal/Grid Photocoagulation
    DescriptionThe first occurrence of focal/grid photocoagulation regardless of diabetic macular edema (DME) distance from the center of the macula.
    Time FrameBaseline through 36 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population including all randomized participants analyzed according to the treatment group to which they were originally assigned by random allocation even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants371360
    Yes
    32
    8.6%
    27
    7.5%
    No
    339
    91.4%
    333
    92.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ruboxistaurin, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.577
    CommentsP-value is for first occurrence of focal/grid photocoagulation yes versus no.
    MethodChi-squared
    Comments
    4. Secondary Outcome
    TitleChange From Baseline in Contrast Sensitivity by Pelli-Robson
    DescriptionPelli-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.
    Time FrameBaseline, 36 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population: all randomized participants analyzed according to treatment group to which they were originally assigned by random allocation even if they did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants371360
    Measure DR Study Eyes718689
    Baseline (letters correct) (n=718,689)
    33.54
    (3.33)
    33.71
    (3.54)
    Change from baseline (n=685,664)
    -0.54
    (3.84)
    -1.06
    (4.68)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ruboxistaurin, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.041
    CommentsP-value is for change from baseline.
    MethodANCOVA
    Comments
    Method of EstimationEstimation ParameterMean Difference (Final Values)
    Estimated Value0.45
    Confidence Interval (2-Sided) 95%
    0.02 to 0.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    TitleProgression of Nonproliferative Diabetic Retinopathy (DR) by Seven-field Stereo Fundus Photography
    DescriptionParticipants 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.
    Time FrameBaseline through 36 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population including all randomized participants analyzed according to the treatment group to which they were originally assigned by random allocation even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants371360
    No progression
    328
    88.4%
    312
    86.7%
    Progression
    43
    11.6%
    48
    13.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ruboxistaurin, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.475
    CommentsP-value is for progression of nonproliferative diabetic retinopathy (DR) by seven-field stereo fundus photography progression versus no progression.
    MethodChi-squared
    Comments
    6. Secondary Outcome
    TitleChange From Baseline in Estimated Glomerular Filtration Rate
    DescriptionThe 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.
    Time FrameBaseline, 36 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population including all randomized participants analyzed according to the treatment group to which they were originally assigned by random allocation even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants368358
    Baseline (n=368,358)
    85.35
    (22.24)
    87.27
    (23.44)
    Change from baseline (n=340,328)
    -5.55
    (15.70)
    -7.92
    (17.31)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ruboxistaurin, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.211
    CommentsP-value is for change from baseline.
    MethodANCOVA
    Comments
    Method of EstimationEstimation ParameterMean Difference (Final Values)
    Estimated Value1.52
    Confidence Interval (2-Sided) 95%
    -0.87 to 3.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    TitleChange From Baseline at Endpoint in Albumin/Creatinine Ratio
    Description
    Time Frame36 Months

    Outcome Measure Data

    Analysis Population Description
    The completer population includes participants who completed all 36 months of the treatment phase.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants270261
    Baseline (n=270,261)
    123.53
    (507.93)
    152.61
    (623.98)
    Change from baseline (n=267,253)
    135.90
    (865.34)
    72.69
    (720.35)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ruboxistaurin, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.365
    CommentsP-value is for change from baseline.
    Methodt-test, 2 sided
    Comments
    Method of EstimationEstimation ParameterMean Difference (Final Values)
    Estimated Value63.22
    Confidence Interval (2-Sided) 95%
    -73.68 to 200.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    TitleChange From Baseline at Endpoint in Visual Function by the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) at 36 Months
    Description25 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.
    Time Frame36 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population including all randomized participants analyzed according to the treatment group to which they were originally assigned by random allocation even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants351342
    Baseline (n=351,342)
    67.86
    (8.25)
    67.56
    (7.85)
    Change from baseline (n=314,309)
    0.17
    (6.21)
    -1.36
    (8.56)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ruboxistaurin, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.009
    CommentsP-value is for change from baseline.
    MethodANCOVA
    Comments
    Method of EstimationEstimation ParameterMean Difference (Final Values)
    Estimated Value1.52
    Confidence Interval (2-Sided) 95%
    0.38 to 2.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    TitleNumber of Participants With Adverse Events
    DescriptionSummaries of serious adverse events (SAEs) and all other non-serious adverse events (AEs) are located in the Reported Adverse Event Module.
    Time FrameBaseline through 36 Months

    Outcome Measure Data

    Analysis Population Description
    Safety population: all randomized participants who received at least one dose of study drug.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants371360
    Serious adverse events
    93
    25.1%
    82
    22.8%
    Adverse events
    298
    80.3%
    299
    83.1%
    10. Primary Outcome
    TitleOccurrence of Sustained Moderate Visual Loss (SMVL) in a Diabetic Retinopathy (DR) Study Eye
    DescriptionThe 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.
    Time FrameBaseline, 36 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population: all randomized participants with at least 1 eligible study eye analyzed according to the treatment group to which they were originally assigned by random allocation even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    Measure Participants342331
    Yes
    8
    2.2%
    16
    4.4%
    No
    334
    90%
    315
    87.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ruboxistaurin, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesisp-Value0.081
    CommentsP-value is for occurrence of sustained moderate visual loss (SMVL) in a diabetic retinopathy (DR) study eye yes versus no.
    MethodChi-squared
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value0.47
    Confidence Interval (2-Sided) 95%
    0.20 to 1.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group TitleRuboxistaurinPlacebo
    Arm/Group Description32 mg once daily (QD) oral for up to 36 monthsQD oral for up to 36 months
    All Cause Mortality
    RuboxistaurinPlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN)
    Serious Adverse Events
    RuboxistaurinPlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total93/371 (25.1%) 82/360 (22.8%)
    Blood and lymphatic system disorders
    Anaemia3/371 (0.8%) 40/360 (0%) 0
    Thrombocytopenia1/371 (0.3%) 10/360 (0%) 0
    Cardiac disorders
    Acute myocardial infarction2/371 (0.5%) 35/360 (1.4%) 5
    Angina pectoris4/371 (1.1%) 141/360 (0.3%) 1
    Angina unstable3/371 (0.8%) 42/360 (0.6%) 2
    Aortic valve stenosis1/371 (0.3%) 10/360 (0%) 0
    Arteriosclerosis coronary artery1/371 (0.3%) 100/360 (0%) 0
    Atrial fibrillation2/371 (0.5%) 51/360 (0.3%) 2
    Atrial flutter1/371 (0.3%) 41/360 (0.3%) 1
    Atrioventricular block1/371 (0.3%) 10/360 (0%) 0
    Cardiac arrest2/371 (0.5%) 20/360 (0%) 0
    Cardiac failure0/371 (0%) 01/360 (0.3%) 8
    Cardiac failure congestive1/371 (0.3%) 42/360 (0.6%) 9
    Cardiogenic shock0/371 (0%) 01/360 (0.3%) 1
    Cardiovascular disorder1/371 (0.3%) 10/360 (0%) 0
    Cor pulmonale1/371 (0.3%) 40/360 (0%) 0
    Coronary artery disease3/371 (0.8%) 95/360 (1.4%) 16
    Coronary artery occlusion0/371 (0%) 02/360 (0.6%) 2
    Ischaemic cardiomyopathy1/371 (0.3%) 20/360 (0%) 0
    Left ventricular failure1/371 (0.3%) 10/360 (0%) 0
    Myocardial infarction6/371 (1.6%) 64/360 (1.1%) 4
    Myocardial ischaemia0/371 (0%) 01/360 (0.3%) 1
    Stress cardiomyopathy1/371 (0.3%) 10/360 (0%) 0
    Tachycardia1/371 (0.3%) 11/360 (0.3%) 1
    Ear and labyrinth disorders
    Hearing impaired0/371 (0%) 01/360 (0.3%) 11
    Vertigo1/371 (0.3%) 11/360 (0.3%) 1
    Endocrine disorders
    Goitre1/371 (0.3%) 80/360 (0%) 0
    Eye disorders
    Cataract0/371 (0%) 02/360 (0.6%) 7
    Ocular myasthenia1/371 (0.3%) 40/360 (0%) 0
    Retinal detachment1/371 (0.3%) 10/360 (0%) 0
    Visual disturbance1/371 (0.3%) 10/360 (0%) 0
    Gastrointestinal disorders
    Colitis0/371 (0%) 01/360 (0.3%) 1
    Diarrhoea1/371 (0.3%) 21/360 (0.3%) 1
    Faecal incontinence1/371 (0.3%) 21/360 (0.3%) 1
    Gastritis0/371 (0%) 01/360 (0.3%) 1
    Gastrointestinal ulcer haemorrhage1/371 (0.3%) 10/360 (0%) 0
    Lower gastrointestinal haemorrhage0/371 (0%) 01/360 (0.3%) 1
    Mouth ulceration0/371 (0%) 01/360 (0.3%) 1
    Oesophageal ulcer0/371 (0%) 01/360 (0.3%) 1
    Pancreatitis0/371 (0%) 01/360 (0.3%) 1
    Pancreatitis acute0/371 (0%) 01/360 (0.3%) 1
    Umbilical hernia1/371 (0.3%) 10/360 (0%) 0
    Vomiting0/371 (0%) 01/360 (0.3%) 1
    General disorders
    Calcinosis1/371 (0.3%) 30/360 (0%) 0
    Chest discomfort1/371 (0.3%) 11/360 (0.3%) 2
    Chest pain3/371 (0.8%) 31/360 (0.3%) 1
    Death0/371 (0%) 03/360 (0.8%) 3
    Impaired healing0/371 (0%) 01/360 (0.3%) 4
    Pyrexia1/371 (0.3%) 10/360 (0%) 0
    Hepatobiliary disorders
    Cholecystitis1/371 (0.3%) 11/360 (0.3%) 1
    Cholecystitis acute0/371 (0%) 01/360 (0.3%) 1
    Cholelithiasis0/371 (0%) 01/360 (0.3%) 1
    Immune system disorders
    Anaphylactic reaction0/371 (0%) 01/360 (0.3%) 1
    Infections and infestations
    Appendicitis0/371 (0%) 01/360 (0.3%) 1
    Bacteraemia0/371 (0%) 01/360 (0.3%) 1
    Cystitis1/371 (0.3%) 20/360 (0%) 0
    Dengue fever0/371 (0%) 01/360 (0.3%) 1
    Diarrhoea infectious0/371 (0%) 01/360 (0.3%) 1
    Endocarditis1/371 (0.3%) 10/360 (0%) 0
    Gastroenteritis2/371 (0.5%) 22/360 (0.6%) 2
    Gastroenteritis viral0/371 (0%) 01/360 (0.3%) 1
    Herpes zoster1/371 (0.3%) 10/360 (0%) 0
    Liver abscess1/371 (0.3%) 20/360 (0%) 0
    Lobar pneumonia1/371 (0.3%) 10/360 (0%) 0
    Localised infection2/371 (0.5%) 20/360 (0%) 0
    Osteomyelitis1/371 (0.3%) 10/360 (0%) 0
    Perirectal abscess0/371 (0%) 01/360 (0.3%) 1
    Pneumonia3/371 (0.8%) 31/360 (0.3%) 1
    Pyelonephritis0/371 (0%) 02/360 (0.6%) 2
    Pyelonephritis acute1/371 (0.3%) 10/360 (0%) 0
    Sepsis0/371 (0%) 01/360 (0.3%) 1
    Subcutaneous abscess1/371 (0.3%) 10/360 (0%) 0
    Urinary tract infection0/371 (0%) 02/360 (0.6%) 2
    Urinary tract infection fungal1/371 (0.3%) 10/360 (0%) 0
    Wound infection0/371 (0%) 01/360 (0.3%) 1
    Injury, poisoning and procedural complications
    Ankle fracture3/371 (0.8%) 60/360 (0%) 0
    Cerebral haemorrhage traumatic1/371 (0.3%) 10/360 (0%) 0
    Chest injury1/371 (0.3%) 10/360 (0%) 0
    Concussion1/371 (0.3%) 10/360 (0%) 0
    Device occlusion0/371 (0%) 01/360 (0.3%) 1
    Fall3/371 (0.8%) 50/360 (0%) 0
    Foot fracture1/371 (0.3%) 10/360 (0%) 0
    Head injury1/371 (0.3%) 10/360 (0%) 0
    Hip fracture2/371 (0.5%) 20/360 (0%) 0
    Jaw fracture1/371 (0.3%) 10/360 (0%) 0
    Pelvic fracture1/371 (0.3%) 20/360 (0%) 0
    Road traffic accident1/371 (0.3%) 10/360 (0%) 0
    Spinal fracture1/371 (0.3%) 10/360 (0%) 0
    Subdural haemorrhage1/371 (0.3%) 10/360 (0%) 0
    Therapeutic agent toxicity0/371 (0%) 01/360 (0.3%) 1
    Wound1/371 (0.3%) 10/360 (0%) 0
    Wrist fracture1/371 (0.3%) 20/360 (0%) 0
    Investigations
    Blood glucose increased1/371 (0.3%) 10/360 (0%) 0
    Colonoscopy0/371 (0%) 01/360 (0.3%) 1
    Electrocardiogram abnormal0/371 (0%) 01/360 (0.3%) 1
    Metabolism and nutrition disorders
    Dehydration1/371 (0.3%) 12/360 (0.6%) 2
    Diabetes mellitus inadequate control5/371 (1.3%) 96/360 (1.7%) 6
    Diabetic foot0/371 (0%) 02/360 (0.6%) 7
    Diabetic ketoacidosis1/371 (0.3%) 10/360 (0%) 0
    Fluid retention0/371 (0%) 01/360 (0.3%) 1
    Hyperglycaemia1/371 (0.3%) 11/360 (0.3%) 1
    Hypoglycaemia3/371 (0.8%) 32/360 (0.6%) 2
    Hypokalaemia1/371 (0.3%) 10/360 (0%) 0
    Hyponatraemia1/371 (0.3%) 10/360 (0%) 0
    Obesity2/371 (0.5%) 100/360 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthritis0/371 (0%) 01/360 (0.3%) 1
    Back pain1/371 (0.3%) 11/360 (0.3%) 2
    Cervical spinal stenosis0/371 (0%) 01/360 (0.3%) 3
    Dupuytren's contracture1/371 (0.3%) 10/360 (0%) 0
    Foot deformity1/371 (0.3%) 100/360 (0%) 0
    Intervertebral disc protrusion1/371 (0.3%) 11/360 (0.3%) 1
    Lumbar spinal stenosis0/371 (0%) 01/360 (0.3%) 4
    Osteitis0/371 (0%) 01/360 (0.3%) 1
    Osteoarthritis0/371 (0%) 02/360 (0.6%) 11
    Rhabdomyolysis1/371 (0.3%) 10/360 (0%) 0
    Spinal osteoarthritis1/371 (0.3%) 10/360 (0%) 0
    Spondylolisthesis0/371 (0%) 01/360 (0.3%) 1
    Tendonitis1/371 (0.3%) 140/360 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Angioimmunoblastic t-cell lymphoma1/371 (0.3%) 10/360 (0%) 0
    Bladder transitional cell carcinoma0/371 (0%) 01/360 (0.3%) 1
    Breast cancer0/371 (0%) 01/360 (0.3%) 4
    Colon adenoma0/371 (0%) 01/360 (0.3%) 1
    Colon cancer0/371 (0%) 01/360 (0.3%) 1
    Colorectal cancer1/371 (0.3%) 10/360 (0%) 0
    Gastric cancer stage iii0/371 (0%) 01/360 (0.3%) 1
    Meningioma0/371 (0%) 01/360 (0.3%) 5
    Pancreatic carcinoma2/371 (0.5%) 21/360 (0.3%) 1
    Prostatic adenoma1/371 (0.3%) 10/360 (0%) 0
    Renal cancer metastatic0/371 (0%) 01/360 (0.3%) 1
    Small intestine carcinoma0/371 (0%) 01/360 (0.3%) 1
    Squamous cell carcinoma of skin0/371 (0%) 01/360 (0.3%) 1
    Thyroid cancer1/371 (0.3%) 30/360 (0%) 0
    Nervous system disorders
    Balance disorder1/371 (0.3%) 10/360 (0%) 0
    Carotid artery stenosis2/371 (0.5%) 40/360 (0%) 0
    Carpal tunnel syndrome1/371 (0.3%) 40/360 (0%) 0
    Cerebral ischaemia1/371 (0.3%) 70/360 (0%) 0
    Cerebrovascular accident4/371 (1.1%) 52/360 (0.6%) 3
    Coma hepatic1/371 (0.3%) 10/360 (0%) 0
    Coordination abnormal0/371 (0%) 01/360 (0.3%) 1
    Cubital tunnel syndrome1/371 (0.3%) 10/360 (0%) 0
    Diabetic hyperglycaemic coma1/371 (0.3%) 10/360 (0%) 0
    Dysarthria1/371 (0.3%) 10/360 (0%) 0
    Facial palsy1/371 (0.3%) 10/360 (0%) 0
    Grand mal convulsion1/371 (0.3%) 90/360 (0%) 0
    Ischaemic stroke2/371 (0.5%) 70/360 (0%) 0
    Loss of consciousness1/371 (0.3%) 10/360 (0%) 0
    Peripheral sensory neuropathy0/371 (0%) 01/360 (0.3%) 1
    Sciatica1/371 (0.3%) 10/360 (0%) 0
    Simple partial seizures1/371 (0.3%) 10/360 (0%) 0
    Syncope1/371 (0.3%) 10/360 (0%) 0
    Transient ischaemic attack2/371 (0.5%) 20/360 (0%) 0
    Psychiatric disorders
    Anxiety0/371 (0%) 01/360 (0.3%) 5
    Confusional state1/371 (0.3%) 10/360 (0%) 0
    Conversion disorder1/371 (0.3%) 10/360 (0%) 0
    Depression1/371 (0.3%) 120/360 (0%) 0
    Suicidal ideation1/371 (0.3%) 40/360 (0%) 0
    Renal and urinary disorders
    Diabetic nephropathy2/371 (0.5%) 70/360 (0%) 0
    Dysuria1/371 (0.3%) 10/360 (0%) 0
    Nephrolithiasis1/371 (0.3%) 10/360 (0%) 0
    Pelvi-ureteric obstruction0/371 (0%) 01/360 (0.3%) 9
    Renal artery arteriosclerosis1/371 (0.3%) 10/360 (0%) 0
    Renal failure3/371 (0.8%) 110/360 (0%) 0
    Renal failure acute0/371 (0%) 01/360 (0.3%) 1
    Renal failure chronic1/371 (0.3%) 40/360 (0%) 0
    Renal impairment0/371 (0%) 01/360 (0.3%) 1
    Urge incontinence0/371 (0%) 01/360 (0.3%) 1
    Urinary retention1/371 (0.3%) 40/360 (0%) 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia1/371 (0.3%) 42/360 (0.6%) 15
    Ovarian cyst0/371 (0%) 01/360 (0.3%) 1
    Pelvic pain0/371 (0%) 01/360 (0.3%) 1
    Priapism0/371 (0%) 01/360 (0.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Asthma0/371 (0%) 01/360 (0.3%) 8
    Dyspnoea0/371 (0%) 03/360 (0.8%) 3
    Epistaxis1/371 (0.3%) 10/360 (0%) 0
    Hypoxia1/371 (0.3%) 10/360 (0%) 0
    Obstructive airways disorder0/371 (0%) 01/360 (0.3%) 2
    Pulmonary embolism0/371 (0%) 01/360 (0.3%) 1
    Sleep apnoea syndrome1/371 (0.3%) 41/360 (0.3%) 4
    Skin and subcutaneous tissue disorders
    Diabetic neuropathic ulcer1/371 (0.3%) 10/360 (0%) 0
    Idiopathic urticaria0/371 (0%) 01/360 (0.3%) 1
    Skin necrosis1/371 (0.3%) 10/360 (0%) 0
    Skin ulcer1/371 (0.3%) 10/360 (0%) 0
    Surgical and medical procedures
    Cholecystectomy0/371 (0%) 01/360 (0.3%) 1
    Splenectomy0/371 (0%) 01/360 (0.3%) 1
    Thyroidectomy1/371 (0.3%) 10/360 (0%) 0
    Tooth extraction0/371 (0%) 01/360 (0.3%) 1
    Vascular disorders
    Aortic stenosis1/371 (0.3%) 130/360 (0%) 0
    Arteriosclerosis1/371 (0.3%) 10/360 (0%) 0
    Circulatory collapse1/371 (0.3%) 10/360 (0%) 0
    Deep vein thrombosis1/371 (0.3%) 40/360 (0%) 0
    Haemorrhage0/371 (0%) 01/360 (0.3%) 3
    Peripheral arterial occlusive disease1/371 (0.3%) 10/360 (0%) 0
    Peripheral ischaemia0/371 (0%) 01/360 (0.3%) 1
    Peripheral vascular disorder2/371 (0.5%) 112/360 (0.6%) 5
    Subclavian artery stenosis1/371 (0.3%) 10/360 (0%) 0
    Vasculitis0/371 (0%) 01/360 (0.3%) 1
    Other (Not Including Serious) Adverse Events
    RuboxistaurinPlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total298/371 (80.3%) 299/360 (83.1%)
    Gastrointestinal disorders
    Diarrhoea38/371 (10.2%) 9032/360 (8.9%) 108
    Nausea17/371 (4.6%) 2321/360 (5.8%) 60
    Vomiting19/371 (5.1%) 2217/360 (4.7%) 25
    General disorders
    Oedema peripheral16/371 (4.3%) 6024/360 (6.7%) 86
    Pyrexia15/371 (4%) 1819/360 (5.3%) 19
    Infections and infestations
    Bronchitis19/371 (5.1%) 2816/360 (4.4%) 23
    Influenza47/371 (12.7%) 6736/360 (10%) 58
    Nasopharyngitis65/371 (17.5%) 13559/360 (16.4%) 121
    Sinusitis24/371 (6.5%) 5413/360 (3.6%) 20
    Upper respiratory tract infection17/371 (4.6%) 2520/360 (5.6%) 34
    Urinary tract infection20/371 (5.4%) 4218/360 (5%) 40
    Metabolism and nutrition disorders
    Hypercholesterolaemia28/371 (7.5%) 12929/360 (8.1%) 131
    Musculoskeletal and connective tissue disorders
    Arthralgia27/371 (7.3%) 8935/360 (9.7%) 144
    Back pain29/371 (7.8%) 9336/360 (10%) 105
    Musculoskeletal pain16/371 (4.3%) 5624/360 (6.7%) 83
    Pain in extremity32/371 (8.6%) 8222/360 (6.1%) 99
    Nervous system disorders
    Headache37/371 (10%) 10244/360 (12.2%) 129
    Respiratory, thoracic and mediastinal disorders
    Cough38/371 (10.2%) 7346/360 (12.8%) 85
    Pharyngolaryngeal pain21/371 (5.7%) 3624/360 (6.7%) 36
    Vascular disorders
    Hypertension43/371 (11.6%) 22949/360 (13.6%) 282

    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/Titleinfo@chroma-derm.com
    OrganizationChromaderm
    Phone
    Emailinfo@chroma-derm.com
    Responsible Party:
    Chromaderm, Inc.
    ClinicalTrials.gov Identifier:
    NCT00090519
    Other Study ID Numbers:
    • 8211
    • B7A-MC-MBDL
    First Posted:
    Aug 31, 2004
    Last Update Posted:
    Oct 6, 2016
    Last Verified:
    Aug 1, 2016