Diabetic Retinopathy
Conditions
Brief summary
To provide ruboxistaurin treatment to patients who completed the B7A-MC-MBCM study (NCT00604383), and who are felt by the investigator to have the potential to benefit from the ruboxistaurin treatment. Patients must be off study drug for 6 to 18 months from completion of B7A-MC-MBCM before beginning B7A-MC-MBDV. Additional data will be gathered to determine the long-term safety and effect of ruboxistaurin on vision.
Interventions
DRUGRuboxistaurin
32-milligram (mg) tablet, orally, once daily (QD) for up to 2 years.
Sponsors
Chromaderm, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients that completed Month 36 (Visit 15) of the study B7A-MC-MBCM, and the investigator believes he/she would benefit from ruboxistaurin treatment.
Exclusion criteria
* Patients that discontinued from the study B7A-MC-MBCM and/or the investigator does not believe he/she would benefit from ruboxistaurin treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Moderate Visual Loss (SMVL) | Baseline, 18 months up to 24 months | The number of participants who experienced SMVL in at least 1 diabetic retinopathy (DR) study eye. SMVL was a ≥15-letter decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) that was sustained for the last 6 months of the study. Best-corrected ETDRS VA was measured at 4 meters (m) using an eye chart with 5 letters per row of decreasing letter size in each successive row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed. Best-corrected ETDRS VA scores ranged from 0 (no letters read correctly) to 100 (all letters read correctly). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Moderate Vision Loss (SMVL), Long Term | Baseline in Study MBCM, 18 months up to 24 months in Study MBDV (for a total of 75 up to 87 months of SMVL, long term) | The number of participants who experienced SMVL, long term, in at least 1 diabetic retinopathy (DR) study eye. Long term SMVL was a ≥15-letter decrease from Study MBCM baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) that was sustained for the last 6 months of Study MBDV. VA was measured at 4 meters (m) using an eye chart with 5 letters per row of decreasing letter size in each successive row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed. Best-corrected ETDRS VA scores ranged from 0 (no letters read correctly) to 100 (all letters read correctly). |
| Number of Participants With a Modified Sustained Moderate Vision Loss (mSMVL) Event by Time Interval | Baseline up to 6 months, 6 months up to 12 months, 12 months up to 18 months, 18 months up to 24 months, and 24 months up to 30 months | An mSMVL event was defined as a ≥15-letter decrease from Study MBDV baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) during any 6-month period, not just the last 6 months of the study. An mSMVL event was the first occurrence of an mSMVL in a participant, and the time at which the mSMVL began was used as the time of the event for the analysis. VA was measured at 4 meters (m) using an eye chart with 5 letters per row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed. |
| Vision Loss | End of Study MBCM to the beginning of Study MBDV, approximately 6 to 18 months | The number of participants whose best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) in at least 1 diabetic retinopathy (DR) study eye decreased by 15-letters or less from the conclusion of Study MBCM to the start of Study MBDV, 6 to 18 months later. Best-corrected ETDRS VA was measured at 4 meters (m) using an eye chart with 5 letters per row of decreasing letter size in each successive row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed. Best-corrected ETDRS VA scores ranged from 0 (no letters read correctly) to 100 (all letters read correctly). |
| Number of Participants Receiving Treatment With Focal/Grid Photocoagulation | Baseline up to Month 24 | — |
| Number of Participants Receiving Treatment With Panretinal Photocoagulation | Baseline up to Month 24 | — |
| Visual Acuity | Month 24 | Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) was measured at 4 meters (m) using an eye chart with 5 letters per row of decreasing letter size in each successive row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed. Best-corrected ETDRS VA scores ranged from 0 (no letters read correctly) to 100 (all letters read correctly). A higher score represented better VA. |
Countries
United States
Participant flow
Recruitment details
This study, B7A-MC-MBDV (MBDV), was an open-label extension of Study B7A-MC-MBCM (MBCM; NCT00604383), and was only open to participants who completed Study MBCM. Unless otherwise stated, the time frames refer to this study, MBDV.
Participants by arm
| Arm | Count |
|---|---|
| Ruboxistaurin 32 mg given once daily as oral tablet for 2 years. | 203 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 9 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 15 |
Baseline characteristics
| Characteristic | Ruboxistaurin |
|---|---|
| Age, Continuous | 58.50 years STANDARD_DEVIATION 9.7 |
| Blood Pressure Diastolic Blood Pressure | 73.29 millimeters of mercury (mm Hg) STANDARD_DEVIATION 10.07 |
| Blood Pressure Systolic Blood Pressure | 131.48 millimeters of mercury (mm Hg) STANDARD_DEVIATION 17.03 |
| Body Mass Index | 33.47 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 7.34 |
| Diabetes Type Type 1 | 24 participants |
| Diabetes Type Type 2 | 179 participants |
| Duration of Diabetes | 16.08 years STANDARD_DEVIATION 8.4 |
| Number of Diabetic Retinopathy (DR) Study Eyes Per Participant One | 72 participant |
| Number of Diabetic Retinopathy (DR) Study Eyes Per Participant Two | 131 participant |
| Race/Ethnicity, Customized Caucasian | 180 participants |
| Race/Ethnicity, Customized Non-Caucasian | 23 participants |
| Region of Enrollment United States | 203 participants |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 133 Participants |
| Visual Acuity (VA) Score | 76.84 letters read correctly STANDARD_DEVIATION 13.11 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 166 / 203 |
| serious Total, serious adverse events | 57 / 203 |
Outcome results
Primary
Sustained Moderate Visual Loss (SMVL)
The number of participants who experienced SMVL in at least 1 diabetic retinopathy (DR) study eye. SMVL was a ≥15-letter decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) that was sustained for the last 6 months of the study. Best-corrected ETDRS VA was measured at 4 meters (m) using an eye chart with 5 letters per row of decreasing letter size in each successive row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed. Best-corrected ETDRS VA scores ranged from 0 (no letters read correctly) to 100 (all letters read correctly).
Time frame: Baseline, 18 months up to 24 months
Population: All enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruboxistaurin | Sustained Moderate Visual Loss (SMVL) | 10 participants |
Secondary
Number of Participants Receiving Treatment With Focal/Grid Photocoagulation
Time frame: Baseline up to Month 24
Population: All enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruboxistaurin | Number of Participants Receiving Treatment With Focal/Grid Photocoagulation | 19 participants |
Secondary
Number of Participants Receiving Treatment With Panretinal Photocoagulation
Time frame: Baseline up to Month 24
Population: All enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruboxistaurin | Number of Participants Receiving Treatment With Panretinal Photocoagulation | 53 participants |
Secondary
Number of Participants With a Modified Sustained Moderate Vision Loss (mSMVL) Event by Time Interval
An mSMVL event was defined as a ≥15-letter decrease from Study MBDV baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) during any 6-month period, not just the last 6 months of the study. An mSMVL event was the first occurrence of an mSMVL in a participant, and the time at which the mSMVL began was used as the time of the event for the analysis. VA was measured at 4 meters (m) using an eye chart with 5 letters per row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed.
Time frame: Baseline up to 6 months, 6 months up to 12 months, 12 months up to 18 months, 18 months up to 24 months, and 24 months up to 30 months
Population: All enrolled participants (pts) at risk during the specified intervals. Pts who did not experience an event during the interval were censored to the last time point in the interval. Number of pts censored: 0 to 6 months = 2 pts, 6 to 12 months = 4 pts, 12 to 18 months = 9 pts, 18 to 24 months = 82 pts, and 24 to 30 months = 90 pts.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruboxistaurin | Number of Participants With a Modified Sustained Moderate Vision Loss (mSMVL) Event by Time Interval | 24 up to 30 months, n=90 | 0 participants |
| Ruboxistaurin | Number of Participants With a Modified Sustained Moderate Vision Loss (mSMVL) Event by Time Interval | 12 up to 18 months, n=188 | 5 participants |
| Ruboxistaurin | Number of Participants With a Modified Sustained Moderate Vision Loss (mSMVL) Event by Time Interval | 18 up to 24 months, n=174 | 2 participants |
| Ruboxistaurin | Number of Participants With a Modified Sustained Moderate Vision Loss (mSMVL) Event by Time Interval | 0 up to 6 months, n=198 | 0 participants |
| Ruboxistaurin | Number of Participants With a Modified Sustained Moderate Vision Loss (mSMVL) Event by Time Interval | 6 up to 12 months, n=196 | 4 participants |
Secondary
Sustained Moderate Vision Loss (SMVL), Long Term
The number of participants who experienced SMVL, long term, in at least 1 diabetic retinopathy (DR) study eye. Long term SMVL was a ≥15-letter decrease from Study MBCM baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) that was sustained for the last 6 months of Study MBDV. VA was measured at 4 meters (m) using an eye chart with 5 letters per row of decreasing letter size in each successive row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed. Best-corrected ETDRS VA scores ranged from 0 (no letters read correctly) to 100 (all letters read correctly).
Time frame: Baseline in Study MBCM, 18 months up to 24 months in Study MBDV (for a total of 75 up to 87 months of SMVL, long term)
Population: Participants who were treated with 32 milligram (mg) ruboxistaurin once daily in Study MBCM and had at least 1 DR study eye, who were also enrolled in Study MBDV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruboxistaurin | Sustained Moderate Vision Loss (SMVL), Long Term | 8 participants |
Secondary
Vision Loss
The number of participants whose best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) in at least 1 diabetic retinopathy (DR) study eye decreased by 15-letters or less from the conclusion of Study MBCM to the start of Study MBDV, 6 to 18 months later. Best-corrected ETDRS VA was measured at 4 meters (m) using an eye chart with 5 letters per row of decreasing letter size in each successive row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed. Best-corrected ETDRS VA scores ranged from 0 (no letters read correctly) to 100 (all letters read correctly).
Time frame: End of Study MBCM to the beginning of Study MBDV, approximately 6 to 18 months
Population: All enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruboxistaurin | Vision Loss | 22 participants |
Secondary
Visual Acuity
Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) was measured at 4 meters (m) using an eye chart with 5 letters per row of decreasing letter size in each successive row. Participants read the chart from the top down until reaching a row where ≥3 letters in the row could not be read correctly. If \<20 letters were read correctly at 4 m, the chart was re-read at 1 m. The best-corrected ETDRS VA score was the total number of letters read correctly per eye at 4 m, plus a correction factor of 30 if ≥20 letters were read correctly at 4 m, plus the total number of letters read correctly at 1 m, if assessed. Best-corrected ETDRS VA scores ranged from 0 (no letters read correctly) to 100 (all letters read correctly). A higher score represented better VA.
Time frame: Month 24
Population: All enrolled participants. Last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ruboxistaurin | Visual Acuity | 75.14 letters read correctly | Standard Deviation 14.92 |