Diabetic Retinopathy
Conditions
Brief summary
This study is to test whether or not 32 milligrams (mg) of ruboxistaurin a day over three years will reduce vision loss associated with diabetic retinopathy.
Interventions
DRUGruboxistaurin
32-mg tablet, orally, daily, up to 42 months
DRUGplacebo
1 tablet, orally, daily, up to 42 months
Sponsors
Chromaderm, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 1 or Type 2 diabetes mellitus * 18 years or older * Meet specific requirements for diabetic retinopathy * Free of severe or chronically disabling conditions, except diabetes, diabetic retinopathy and diabetic macular edema * Hemoglobin A1c (HbA1C) ≤13.0%
Exclusion criteria
* History of panretinal photocoagulation for diabetic retinopathy, conditions that might affect the progression of diabetic retinopathy, or unstable angina * Investigators, site personnel directly affiliated with the study and their families * Presence of eye disorders that may affect the progression of diabetic retinopathy or cause vision loss * Presence of medical disorder, cancer, or elevated laboratory measurements that could represent a safety risk during the study * Women who are pregnant, breastfeeding, intend to become pregnant, or who are sexually active without using an acceptable method of birth control
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Had Sustained Moderate Visual Loss (SMVL) as Defined as a Visual Acuity Loss of ≥15 Letters Measured Twice During a 6-month Period | Baseline through 36 months | SMVL is defined as a ≥15-letter decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) that the participant sustained during the last 6 months of study participation (Months 30-36). Participants who discontinued the study early may have had SMVL if there was a 6-month period of ≥15 letters lost in VA ending with the last visit at which VA was assessed. 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). Percentage of participants = (number of participants who had SMVL) / (number of participants who were randomized) \* 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Developed Center Involved or Imminently Threatened Diabetic Macular Edema (DME) | Baseline through 36 months | DME is the accumulation of extracellular fluid in the retinal tissue of the macular area, which can reduce the ability for fine visual discrimination. Percentage of participants = (number of participants who developed center involved or imminently threatened DME) / (number of participants who had no center involved or imminently threatened DME at baseline) \* 100. |
| Percentage of Participants Who Experienced the Development of Proliferative Diabetic Retinopathy (PDR) | Baseline through 36 months | Percentage of participants = (number of participants who experienced the development of PDR) / (number of participants who were randomized) \* 100. |
| Change From Baseline up to 36 Months in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) | Baseline, up to 36 months | NEI-VFQ-25 consisted of 25 questions and was used to measure the influence of visual disability and symptoms on general health of participants. The possible total score range for the NEI-VFQ-25 was from 0 (worst possible outcome) to 100 (best possible outcome). |
| Change From Baseline up to 36 Months in Mental and Physical Components of the Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Questionnaire | Baseline, up to 36 months | SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions. There are 2 component scores, mental component score (MCS) and physical component score (PCS). MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. Both MCS and PCS have scores ranging from 0 to 100 with higher scores indicating better mental or physical health. |
Countries
United States
Participant flow
Pre-assignment details
This study consisted of a 36-month treatment phase and a 0 to 6-month extended treatment phase. Completers are those who completed the 36-month treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| Ruboxistaurin One 32-mg tablet, orally, daily, for up to 42 months | 345 |
| Placebo 1 tablet, orally, daily, for up to 42 months | 340 |
| Total | 685 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 16 | 9 |
| Overall Study | Death | 14 | 22 |
| Overall Study | Lost to Follow-up | 24 | 19 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Withdrawal by Subject | 33 | 31 |
Baseline characteristics
| Characteristic | Ruboxistaurin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 59.48 years STANDARD_DEVIATION 10.91 | 59.18 years STANDARD_DEVIATION 10.61 | 59.33 years STANDARD_DEVIATION 10.76 |
| Race/Ethnicity, Customized African Descent | 43 participants | 27 participants | 70 participants |
| Race/Ethnicity, Customized Caucasian | 259 participants | 273 participants | 532 participants |
| Race/Ethnicity, Customized East/Southeast Asian | 15 participants | 12 participants | 27 participants |
| Race/Ethnicity, Customized Hispanic | 18 participants | 20 participants | 38 participants |
| Race/Ethnicity, Customized Other | 9 participants | 8 participants | 17 participants |
| Race/Ethnicity, Customized Western Asian | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 345 participants | 340 participants | 685 participants |
| Sex: Female, Male Female | 130 Participants | 122 Participants | 252 Participants |
| Sex: Female, Male Male | 215 Participants | 218 Participants | 433 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 314 / 345 | 322 / 340 |
| serious Total, serious adverse events | 145 / 345 | 157 / 340 |
Outcome results
Primary
Percentage of Participants Who Had Sustained Moderate Visual Loss (SMVL) as Defined as a Visual Acuity Loss of ≥15 Letters Measured Twice During a 6-month Period
SMVL is defined as a ≥15-letter decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) that the participant sustained during the last 6 months of study participation (Months 30-36). Participants who discontinued the study early may have had SMVL if there was a 6-month period of ≥15 letters lost in VA ending with the last visit at which VA was assessed. 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). Percentage of participants = (number of participants who had SMVL) / (number of participants who were randomized) \* 100.
Time frame: Baseline through 36 months
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruboxistaurin | Percentage of Participants Who Had Sustained Moderate Visual Loss (SMVL) as Defined as a Visual Acuity Loss of ≥15 Letters Measured Twice During a 6-month Period | 5.5 percentage of participants |
| Placebo | Percentage of Participants Who Had Sustained Moderate Visual Loss (SMVL) as Defined as a Visual Acuity Loss of ≥15 Letters Measured Twice During a 6-month Period | 9.1 percentage of participants |
p-value: 0.034Cochran-Mantel-Haenszel
Secondary
Change From Baseline up to 36 Months in Mental and Physical Components of the Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Questionnaire
SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions. There are 2 component scores, mental component score (MCS) and physical component score (PCS). MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. Both MCS and PCS have scores ranging from 0 to 100 with higher scores indicating better mental or physical health.
Time frame: Baseline, up to 36 months
Population: All randomized participants with evaluable SF-36 MCS and PCS. LOCF was used to impute missing post-baseline values
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ruboxistaurin | Change From Baseline up to 36 Months in Mental and Physical Components of the Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Questionnaire | MCS | -12.21 units on a scale | Standard Deviation 70.91 |
| Ruboxistaurin | Change From Baseline up to 36 Months in Mental and Physical Components of the Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Questionnaire | PCS | -30.63 units on a scale | Standard Deviation 84.92 |
| Placebo | Change From Baseline up to 36 Months in Mental and Physical Components of the Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Questionnaire | MCS | -19.85 units on a scale | Standard Deviation 70.05 |
| Placebo | Change From Baseline up to 36 Months in Mental and Physical Components of the Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Questionnaire | PCS | -29.15 units on a scale | Standard Deviation 79.41 |
Secondary
Change From Baseline up to 36 Months in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25)
NEI-VFQ-25 consisted of 25 questions and was used to measure the influence of visual disability and symptoms on general health of participants. The possible total score range for the NEI-VFQ-25 was from 0 (worst possible outcome) to 100 (best possible outcome).
Time frame: Baseline, up to 36 months
Population: All randomized participants with evaluable NEI-VFQ-25 total score. Last Observation Carried Forward (LOCF) was used to impute missing post-baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ruboxistaurin | Change From Baseline up to 36 Months in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) | -3.82 units on a scale | Standard Deviation 14.75 |
| Placebo | Change From Baseline up to 36 Months in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) | -4.10 units on a scale | Standard Deviation 13.45 |
Secondary
Percentage of Participants Who Developed Center Involved or Imminently Threatened Diabetic Macular Edema (DME)
DME is the accumulation of extracellular fluid in the retinal tissue of the macular area, which can reduce the ability for fine visual discrimination. Percentage of participants = (number of participants who developed center involved or imminently threatened DME) / (number of participants who had no center involved or imminently threatened DME at baseline) \* 100.
Time frame: Baseline through 36 months
Population: All randomized participants who had no center involved or imminently threatened DME at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruboxistaurin | Percentage of Participants Who Developed Center Involved or Imminently Threatened Diabetic Macular Edema (DME) | 44.4 percentage of participants |
| Placebo | Percentage of Participants Who Developed Center Involved or Imminently Threatened Diabetic Macular Edema (DME) | 49.0 percentage of participants |
Secondary
Percentage of Participants Who Experienced the Development of Proliferative Diabetic Retinopathy (PDR)
Percentage of participants = (number of participants who experienced the development of PDR) / (number of participants who were randomized) \* 100.
Time frame: Baseline through 36 months
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruboxistaurin | Percentage of Participants Who Experienced the Development of Proliferative Diabetic Retinopathy (PDR) | 35.9 percentage of participants |
| Placebo | Percentage of Participants Who Experienced the Development of Proliferative Diabetic Retinopathy (PDR) | 36.5 percentage of participants |