Blepharitis, Dry Eye, Meibomianitis
Conditions
Brief summary
To determine the safety and efficacy of sub-antimicrobial dose COL-101 in the treatment of patients who have both blepharitis and facial rosacea
Interventions
DRUGCOL-101 (doxycycline, USP) capsules
40mg, once per day for 84 days
DRUGplacebo
sugar capsule
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* blepharitis * facial rosacea
Exclusion criteria
* pregnant or nursing women * allergy to tetracyclines * recent eye surgery * past or current use of isotretinoin * patients who are achlorhydric * patients who have had gastric by-pass surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bulbar Conjunctival Hyperemia | Baseline to Week 12 | Bulbar conjunctival hyperemia will be assessed using an ordered categorical value ranging from 0 (Clear) to 4 (Severe). Hyperemia is graded on the following scale and half scores are acceptable: None (0) = normal Mild (1) = slight localized injection Moderate (2) = pink color Severe (3) = red color Very Severe (4) = marked dark redness |
| Change in Ocular Surface Disease Index (OSDI) | Baseline to Week 12 | OSDI is calculated based following formula using 12-question Ocular Surface Disease questionnaire (with each question scored 0-4): OSDI = (D/E)x25, where D = Sum of all scores for questions answered E = Total number of questions answered (not including questions answered NA) Range of OSDI is 0 to 100 (higher score indicates worse condition). |
Countries
United States
Participant flow
Recruitment details
Recruitment time was approximately 6 months in 8 US clinics.
Pre-assignment details
Subjects were screened for eligibility within 6 weeks prior to the baseline visit. This 12-week study employed a two-treatment, parallel-group design with subjects randomized in a 2:1 ratio to active drug or placebo.
Participants by arm
| Arm | Count |
|---|---|
| COL-101 (Doxycycline, USP) Capsules 40 MG, Once per day for 84 days | 46 |
| Placebo Sugar capsule, once per day for 84 days | 24 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | non-compliance | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | COL-101 (Doxycycline, USP) Capsules | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 10 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 36 Participants | 51 Participants |
| Age, Continuous | 58.2 years STANDARD_DEVIATION 14.27 | 54.5 years STANDARD_DEVIATION 13.46 | 55.7 years STANDARD_DEVIATION 13.76 |
| Region of Enrollment United States | 24 participants | 46 participants | 70 participants |
| Sex: Female, Male Female | 13 Participants | 30 Participants | 43 Participants |
| Sex: Female, Male Male | 11 Participants | 16 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 46 | 0 / 24 |
| serious Total, serious adverse events | 1 / 46 | 1 / 24 |
Outcome results
Primary
Change in Bulbar Conjunctival Hyperemia
Bulbar conjunctival hyperemia will be assessed using an ordered categorical value ranging from 0 (Clear) to 4 (Severe). Hyperemia is graded on the following scale and half scores are acceptable: None (0) = normal Mild (1) = slight localized injection Moderate (2) = pink color Severe (3) = red color Very Severe (4) = marked dark redness
Time frame: Baseline to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COL-101 (Doxycycline, USP) Capsules | Change in Bulbar Conjunctival Hyperemia | -0.61 Scores on a scale | Standard Deviation 0.797 |
| Placebo | Change in Bulbar Conjunctival Hyperemia | -0.60 Scores on a scale | Standard Deviation 0.707 |
p-value: 0.578ANCOVA
Primary
Change in Ocular Surface Disease Index (OSDI)
OSDI is calculated based following formula using 12-question Ocular Surface Disease questionnaire (with each question scored 0-4): OSDI = (D/E)x25, where D = Sum of all scores for questions answered E = Total number of questions answered (not including questions answered NA) Range of OSDI is 0 to 100 (higher score indicates worse condition).
Time frame: Baseline to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COL-101 (Doxycycline, USP) Capsules | Change in Ocular Surface Disease Index (OSDI) | -5.15 Scores on a scale | Standard Deviation 14.002 |
| Placebo | Change in Ocular Surface Disease Index (OSDI) | -8.70 Scores on a scale | Standard Deviation 17.719 |
Comparison: It was anticipated that the difference between the treatment groups in mean reduction from baseline in OSDI scores will be approximately 7 points. A pooled standard deviation of 9.0 for the mean change from baseline OSDI score is expected. Under those assumptions a total of approximately 63 evaluable patients (42 COL-101 patients and 21 placebo patients) is sufficient to provide 80% power. The planned enrolment should provide enough evaluable patients to meet these assumptions.p-value: 0.293ANCOVA