Diabetic Macular Edema
Conditions
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.
Interventions
DRUGRuboxistaurin
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Chromaderm, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Time to Focal Photocoagulation | Baseline through 48 months | — |
| 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. |
| 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. |
| Number of Participants Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 | Baseline through 24 months | — |
| Number of Participants Not Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 | Baseline through 24 months | — |
| Number of Participants Requiring Repeat Focal Photocoagulation at Any Time From Baseline Though Month 24 | Baseline through 24 months | Repeat focal photocoagulation is defined as 2 or more focal photocoagulation treatments needed during the study. |
| Change From Baseline to Month 24 in Retinal Thickness at the Center of the Macula | Baseline, up to 24 months | — |
Countries
Canada, Denmark, Germany, Lithuania, Mexico, Portugal, Romania, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Taken orally daily for up to 48 months | 157 |
| Ruboxistaurin 32 milligrams (mg) taken orally daily for up to 48 months | 152 |
| Total | 309 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 9 | 14 |
| Overall Study | Physician Decision | 4 | 3 |
| Overall Study | Protocol Entry Criteria Exclusion | 4 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Sponsor Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 20 | 4 |
Baseline characteristics
| Characteristic | Ruboxistaurin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 9.9 | 55.5 years STANDARD_DEVIATION 9.6 | 55.5 years STANDARD_DEVIATION 9.3 |
| Race/Ethnicity, Customized African Descent | 15 participants | 33 participants | 18 participants |
| Race/Ethnicity, Customized Caucasian | 111 participants | 228 participants | 117 participants |
| Race/Ethnicity, Customized East Asian | 3 participants | 5 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic | 21 participants | 41 participants | 20 participants |
| Race/Ethnicity, Customized West Asian | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Canada | 11 participants | 22 participants | 11 participants |
| Region of Enrollment Denmark | 26 participants | 52 participants | 26 participants |
| Region of Enrollment France | 6 participants | 10 participants | 4 participants |
| Region of Enrollment Germany | 10 participants | 23 participants | 13 participants |
| Region of Enrollment Lithuania | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Mexico | 10 participants | 17 participants | 7 participants |
| Region of Enrollment Portugal | 17 participants | 33 participants | 16 participants |
| Region of Enrollment Romania | 12 participants | 25 participants | 13 participants |
| Region of Enrollment Spain | 9 participants | 18 participants | 9 participants |
| Region of Enrollment United Kingdom | 5 participants | 10 participants | 5 participants |
| Region of Enrollment United States | 46 participants | 98 participants | 52 participants |
| Sex: Female, Male Female | 66 Participants | 133 Participants | 67 Participants |
| Sex: Female, Male Male | 86 Participants | 176 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 112 / 153 | 118 / 149 |
| serious Total, serious adverse events | 31 / 153 | 36 / 149 |
Outcome results
Primary
Percentage of Participants With Sustained Moderate Visual Loss (SMVL) Any Time Baseline Through Month 48
SMVL is defined as a 15 letter or more decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity that is sustained for the participant's last 6 months of study participation. ETDRS visual acuity uses an eye chart with 5 letters per line. The scores range from 0 (no letters read correctly) to 100 (all letters read correctly).
Time frame: Baseline through 48 months
Population: All randomized participants who took at least 1 dose of study drug and had post-baseline SMVL measurements.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Sustained Moderate Visual Loss (SMVL) Any Time Baseline Through Month 48 | 3.4 percent of participants |
| Ruboxistaurin | Percentage of Participants With Sustained Moderate Visual Loss (SMVL) Any Time Baseline Through Month 48 | 2.2 percent of participants |
p-value: 0.72495% CI: [0.15, 2.67]Fisher Exact
Secondary
Change From Baseline to Month 24 in Contrast Sensitivity
Values are presented as changes in the number of letters read correctly on the Pelli-Robson contrast sensitivity chart which consists of 16 triplets (48 letters total) with letters of the same size but decreasing contrast. Least Squares (LS) Mean values were controlled for treatment, pooled center, and baseline value.
Time frame: Baseline, 24 months
Population: All randomized participants who took at least 1 dose of study drug and had both baseline and post-baseline contrast sensitivity measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Month 24 in Contrast Sensitivity | -1.1 letters read correctly | Standard Error 0.4 |
| Ruboxistaurin | Change From Baseline to Month 24 in Contrast Sensitivity | -0.6 letters read correctly | Standard Error 0.4 |
p-value: 0.34495% CI: [-0.6, 1.6]Mixed models repeated measures
Secondary
Change From Baseline to Month 24 in Mean Retinal Thickness Within 500 Microns of the Center of the Macula
Least Squares (LS) Mean values were controlled for treatment, pooled center, and baseline value.
Time frame: Baseline, 24 months
Population: All randomized participants who took at least 1 dose of study drug and had both baseline and post-baseline retinal thickness measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Month 24 in Mean Retinal Thickness Within 500 Microns of the Center of the Macula | 12.8 micrometer (µm) | Standard Error 5.5 |
| Ruboxistaurin | Change From Baseline to Month 24 in Mean Retinal Thickness Within 500 Microns of the Center of the Macula | 9.4 micrometer (µm) | Standard Error 5.3 |
p-value: 0.61695% CI: [-16.5, 9.8]Mixed models repeated measures
Secondary
Change From Baseline to Month 24 in Retinal Thickness at the Center of the Macula
Time frame: Baseline, up to 24 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Month 24 in Retinal Thickness at the Center of the Macula | 10.5 micrometer (µm) | Standard Deviation 65.4 |
| Ruboxistaurin | Change From Baseline to Month 24 in Retinal Thickness at the Center of the Macula | 13.1 micrometer (µm) | Standard Deviation 74.9 |
p-value: 0.663ANCOVA
Secondary
Number of Eyes With Significant Center-Involved Macular Edema at Any Time From Baseline Through Month 24
Significant center-involved macular edema is defined as an absolute retinal thickness at the center of the macula \>2 standard deviations above the mean baseline value (where the mean and standard deviation are calculated at baseline from the randomized population of participants with retinal thickness values of ≤ 300 microns in depth).
Time frame: Baseline through 24 months
Population: All randomized participants who took at least 1 dose of study drug and had post-baseline macular edema measurements.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Eyes With Significant Center-Involved Macular Edema at Any Time From Baseline Through Month 24 | 77 Eyes |
| Ruboxistaurin | Number of Eyes With Significant Center-Involved Macular Edema at Any Time From Baseline Through Month 24 | 76 Eyes |
p-value: 0.97195% CI: [0.68, 1.44]Cochran-Mantel-Haenszel
Secondary
Number of Participants Not Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24
Time frame: Baseline through 24 months
Population: All randomized participants who took at least 1 dose of study drug and had post-baseline determination of focal photocoagulation treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Not Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 | 113 participants |
| Ruboxistaurin | Number of Participants Not Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 | 123 participants |
Secondary
Number of Participants Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24
Time frame: Baseline through 24 months
Population: All randomized participants who took at least 1 dose of study drug and had post-baseline determination of focal photocoagulation treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 | 35 participants |
| Ruboxistaurin | Number of Participants Requiring Focal Photocoagulation at Any Time From Baseline Through Month 24 | 26 participants |
p-value: 0.20395% CI: [0.37, 1.23]Cochran-Mantel-Haenszel
Secondary
Number of Participants Requiring Repeat Focal Photocoagulation at Any Time From Baseline Though Month 24
Repeat focal photocoagulation is defined as 2 or more focal photocoagulation treatments needed during the study.
Time frame: Baseline through 24 months
Population: All randomized participants who took at least 1 dose of study drug and had post-baseline determination of focal photocoagulation treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Requiring Repeat Focal Photocoagulation at Any Time From Baseline Though Month 24 | 11 participants |
| Ruboxistaurin | Number of Participants Requiring Repeat Focal Photocoagulation at Any Time From Baseline Though Month 24 | 12 participants |
p-value: 0.74995% CI: [0.46, 2.92]Cochran-Mantel-Haenszel
Secondary
Time to Focal Photocoagulation
Time frame: Baseline through 48 months
Population: All randomized participants who took at least 1 dose of study drug and had post-baseline determination of focal photocoagulation treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Focal Photocoagulation | NA months |
| Ruboxistaurin | Time to Focal Photocoagulation | NA months |