Blepharitis
Conditions
Keywords
Demodex
Brief summary
The purpose of this study is to compare the safety and efficacy of TP-03, 0.25%, an eyedrop, to its vehicle control for the treatment of blepharitis due to Demodex, a microscopic mite frequently found in human hair follicles. The hypothesis for the study is the proportion of participants cured at Day 43 with treatment by TP-03, 0.25%, is greater than the proportion cured by treatment with its vehicle.
Detailed description
This Phase 2b/3 study is a randomized, controlled, multicenter, double-masked, parallel trial to compare the safety and efficacy of TP-03, 0.25%, to vehicle control for the treatment of Demodex blepharitis. The primary objective of the study is to assess the safety and efficacy of TP-03 compared to its vehicle from Day 1 to Day 43 in adult participants with mild to severe Demodex blepharitis. The primary efficacy endpoint will be cure based upon collarettes. Safety will be determined by assessing adverse effects related to the treatment as well as evaluating any changes in visual acuity, intraocular pressure, slit lamp biomicroscopy and dilated ophthalmoscopy findings.
Interventions
DRUGTP-03, 0.25%
TP-03, lotilaner ophthalmic solution, 0.25%, administered twice a day
DRUGTP-03 Vehicle
Vehicle of TP-03 ophthalmic solution, administered twice a day
Sponsors
Tarsus Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Treatment assignment will be unknown to the study participant, investigators and site staff performing study assessments.
Intervention model description
Active arm: TP-03 0.25% Control arm: Vehicle of TP-03
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be willing to sign the informed consent and deemed capable of complying with the requirements of the study protocol * Meet all of the following criteria in at least one eye: Have more than 10 lashes with collarettes present on the upper lid; have at least mild erythema of the upper eyelid margin; have an average Demodex density, upper and lower eyelids combined, of 1.5 or more mites per lash
Exclusion criteria
* Have used lid hygiene products within 14 days of Screening or unwilling to forego the use of lid hygiene products during the study * Have worn contact lenses within 7 days of Screening or be unwilling to forego contact lens wear during the study * Have used artificial eyelashes or eyelash extensions within 7 days of Screening or be unwilling to forego their use during the study * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Cured Based on a Collarette Score at Day 43. | 43 days | The proportion of participants cured where cure is defined as 0-2 lashes with collarettes on the upper eyelid of the analysis eye. The primary outcome analysis is the combined result from 20 analyses each with missing data imputed. Missing data were imputed per the method described in the SAP. The least square mean is computed from the result of the 20 analyses with imputed missing values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Participants With Eradication of Demodex Mites in the Analysis Eye at Day 43 | 43 days | The proportion of participants with Demodex mites eradicated at Day 43 where eradication is defined as a mite density of 0 mites/lash for the analysis eye. The mite density is obtained by epilating four of more lashes and dividing the number of mites observed under the microscope by the number of lashes. The primary outcome analysis is the combined result from 20 analyses each with missing data imputed. Missing data were imputed per the method described in the SAP. The least square mean is computed from the result of the 20 analyses with imputed missing values |
| Proportion of Participants Cured Based on a Composite Collarette and Erythema Score of 0 in the Analysis Eye at Day 43. | 43 days | The proportion of participants cured where cure is defined as a composite of the collarettes, 0-2 lashes with collarettes on the upper eyelid of the analysis eye, and normal lid margin erythema for the upper eyelid of the analysis eye at Day 43. The primary outcome analysis is the combined result from 20 analyses each with missing data imputed. Missing data were imputed per the method described in the SAP. The least square mean is computed from the result of the 20 analyses with imputed missing values. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active TP-03, lotilaner ophthalmic solution, 0.25%, administered twice a day | 212 |
| Control Vehicle of TP-03 topical ophthalmic solution, administered twice a day | 209 |
| Total | 421 |
Baseline characteristics
| Characteristic | Active | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 126 Participants | 144 Participants | 270 Participants |
| Age, Categorical Between 18 and 65 years | 86 Participants | 65 Participants | 151 Participants |
| Age, Continuous | 66.1 years STANDARD_DEVIATION 12.09 | 67.8 years STANDARD_DEVIATION 12.63 | 67.0 years STANDARD_DEVIATION 12.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 11 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 198 Participants | 198 Participants | 396 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 16 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 195 Participants | 187 Participants | 382 Participants |
| Region of Enrollment United States | 212 participants | 209 participants | 421 participants |
| Sex: Female, Male Female | 123 Participants | 117 Participants | 240 Participants |
| Sex: Female, Male Male | 89 Participants | 92 Participants | 181 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 212 | 0 / 209 |
| other Total, other adverse events | 37 / 212 | 39 / 209 |
| serious Total, serious adverse events | 3 / 212 | 1 / 209 |
Outcome results
Primary
Proportion of Participants Cured Based on a Collarette Score at Day 43.
The proportion of participants cured where cure is defined as 0-2 lashes with collarettes on the upper eyelid of the analysis eye. The primary outcome analysis is the combined result from 20 analyses each with missing data imputed. Missing data were imputed per the method described in the SAP. The least square mean is computed from the result of the 20 analyses with imputed missing values.
Time frame: 43 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Proportion of Participants Cured Based on a Collarette Score at Day 43. | 0.439 Proportion cured | Standard Error 0.034 |
| Control | Proportion of Participants Cured Based on a Collarette Score at Day 43. | 0.072 Proportion cured | Standard Error 0.018 |
Secondary
Proportion of Participants Cured Based on a Composite Collarette and Erythema Score of 0 in the Analysis Eye at Day 43.
The proportion of participants cured where cure is defined as a composite of the collarettes, 0-2 lashes with collarettes on the upper eyelid of the analysis eye, and normal lid margin erythema for the upper eyelid of the analysis eye at Day 43. The primary outcome analysis is the combined result from 20 analyses each with missing data imputed. Missing data were imputed per the method described in the SAP. The least square mean is computed from the result of the 20 analyses with imputed missing values.
Time frame: 43 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Proportion of Participants Cured Based on a Composite Collarette and Erythema Score of 0 in the Analysis Eye at Day 43. | 0.139 Proportion cured | Standard Error 0.024 |
| Control | Proportion of Participants Cured Based on a Composite Collarette and Erythema Score of 0 in the Analysis Eye at Day 43. | 0.01 Proportion cured | Standard Error 0.007 |
Secondary
The Proportion of Participants With Eradication of Demodex Mites in the Analysis Eye at Day 43
The proportion of participants with Demodex mites eradicated at Day 43 where eradication is defined as a mite density of 0 mites/lash for the analysis eye. The mite density is obtained by epilating four of more lashes and dividing the number of mites observed under the microscope by the number of lashes. The primary outcome analysis is the combined result from 20 analyses each with missing data imputed. Missing data were imputed per the method described in the SAP. The least square mean is computed from the result of the 20 analyses with imputed missing values
Time frame: 43 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | The Proportion of Participants With Eradication of Demodex Mites in the Analysis Eye at Day 43 | 0.677 Proportion eradicated | Standard Error 0.032 |
| Control | The Proportion of Participants With Eradication of Demodex Mites in the Analysis Eye at Day 43 | 0.173 Proportion eradicated | Standard Error 0.026 |