Dry Eye Syndromes
Conditions
Keywords
EDE, evaporative dry eye
Brief summary
The objectives of this study are twofold * To evaluate the safety and efficacy of 0.1% AGN-195263 administered twice daily compared to its vehicle in patients with evaporative dry eye (EDE) * To evaluate the systemic pharmacokinetics of 0.1% AGN-195263 administered twice daily in patients with EDE
Interventions
DRUGAGN-195263
1 drop of AGN-195263 will be instilled in each eye twice daily.
DRUGVehicle
1 drop of AGN-195263 vehicle (placebo) will be instilled in each eye twice daily.
Sponsors
Allergan
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
* Male, 18 years of age or older, at the screening (day -51) visit OR * Females, who are naturally postmenopausal (permanent cessation of menstrual periods for at least 12 consecutive months) or are permanently sterilized (ie, eg, tubal occlusion, hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy) at the screening (day -51) visit * In at least 1 eye, all of the following objective measures of evaporative dry eye (EDE) must be present at the standardization (day -21) and baseline (day 1) visits. The same eye must qualify at both visits * Tear film break-up time (TBUT) ≥ 2 seconds and ≤ 7 seconds * Corneal sodium fluorescein staining score ≥ 1 and ≤ 4 (Oxford scheme) * Anesthetized Schirmer's tear test score ≥ 10 mm after 5 minutes * At the standardization (day -21) and baseline (day 1) visits, patients must have: * Ocular Surface Disease Index© (OSDI) score \> 12 (0 to 100 scale) * Overall ocular discomfort score ≥ 1 and \< 4 (0 to 4 scale; 0 = none, 4 = very severe) * Ocular burning score ≥ 1 and \< 4 (0 to 4 scale; 0 = none, 4 = very severe) * Blurred vision score ≥ 1 and \< 4 (0 to 4 scale; 0 = none, 4 = very severe) * In at least 1 eye, a lower lid margin meibum quality global assessment score ≥ 1 at the standardization (day -21) and baseline (day 1) visits. The same eye must qualify at both visits * In at least 1 eye, the number of lower lid margin expressible meibomian glands must be ≥ 3 at the standardization (day -21) and baseline (day 1) visits. The same eye must qualify at both visits * Use of an artificial tear product or lid hygiene (ie, warm compress, lid massage, lid scrub) for the treatment of dry eye disease, EDE or meibomian gland disease within 1 year of the standardization (day -21) visit
Exclusion criteria
* Male patients with a history of, known, or suspected prostate cancer * Male patients with a prostate-specific antigen (PSA) level ≥ 4 μg/L * Female patients with a history of known or suspected breast, cervical, ovarian, or uterine cancer * Female patient who is of child-bearing potential * At standardization (day -21) and / or baseline (day 1) visits, a lower lid margin meibum quality global assessment score of non-expressible (NE) in either eye * Patients who are currently or have used hormone replacement therapy or estrogen and /or progesterone based products (including herbal and nutritional supplements) within 90 days of the standardization (day -21) visit or anticipated use during the study * Patients who are currently using or have used any androgen or anti-androgen treatment (including herbal and nutritional supplements), within 90 days of the standardization (day -21) visit or anticipated use during the study * Patients who are currently using or have used any hair growth product within 90 days of the standardization (day -21) visit or anticipated use during the study * Patients who are currently using or have used corticosteroids administered via any route within 30 days prior to the standardization (day -21) visit, or any anticipated use via any route of administration prior to the month 6 visit * Patients who are currently using or have used oral or topical macrolides, tetracycline, tetracycline derivative drugs (including doxycycline and minocycline), retinoids (eg, isotretinoin), or calcineurin inhibitors (ie, RESTASIS®, Ikervis®) within 60 days of the standardization (day -21) visit, or anticipated use prior to the month 6 visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Ocular Discomfort Score (0 to 4 Scale; 0=None, 4=Very Severe) | 6 month visit | The overall ocular discomfort will be assessed on a questionnaire using a 0 to 4 scale on which 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Tearfilm Break Up Time (TBUT) | Baseline (day 1) to 6 month visit | For TBUT, the mean of 3 measurements of time in seconds will be computed at each visit for each eye. The mean value of the study eye will be used for analysis |
Countries
United States
Participant flow
Recruitment details
Of the 36 participants who enrolled in the study, 18 were randomized and received intervention to comprise the safety and Intent to Treat (ITT) populations
Pre-assignment details
This study was terminated
Participants by arm
| Arm | Count |
|---|---|
| AGN-195263 One drop of 0.1% AGN-195263 instilled in each eye twice daily | 10 |
| Vehicle One drop of AGN-195263 vehicle (placebo) instilled in each eye twice daily. | 8 |
| Enrolled But Not Randomized Run-In period before randomization | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Participants not randomized | 0 | 0 | 18 |
| Overall Study | Study termination by sponsor | 10 | 7 | 0 |
Baseline characteristics
| Characteristic | Vehicle | Enrolled But Not Randomized | Total | AGN-195263 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 9 Participants | 18 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 9 Participants | 18 Participants | 6 Participants |
| BMI | 27.3375 weight (kg) / height (m)^2 STANDARD_DEVIATION 4.8256961932969 | 29.6 weight (kg) / height (m)^2 STANDARD_DEVIATION 7.4233864689013 | 28.1225 weight (kg) / height (m)^2 STANDARD_DEVIATION 1.3197836926109 | 27.43 weight (kg) / height (m)^2 STANDARD_DEVIATION 4.4580376849013 |
| Height | 165.0875 cm STANDARD_DEVIATION 17.14697039567 | 167.63 cm STANDARD_DEVIATION 9.8016438530597 | 165.499 cm STANDARD_DEVIATION 3.7800461794887 | 163.78 cm STANDARD_DEVIATION 8.5922988774833 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 6 Participants | 9 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 10 Participants | 24 Participants | 8 Participants |
| Sex: Female, Male Female | 3 Participants | 12 Participants | 22 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 14 Participants | 3 Participants |
| Weight | 74.3 Kg STANDARD_DEVIATION 16.250384610833 | 82.68 Kg STANDARD_DEVIATION 19.69071093745 | 76.76 Kg STANDARD_DEVIATION 3.5637743007958 | 73.32 Kg STANDARD_DEVIATION 11.022504252664 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 |
| other Total, other adverse events | 0 / 10 | 2 / 8 |
| serious Total, serious adverse events | 0 / 10 | 1 / 8 |
Outcome results
Primary
Overall Ocular Discomfort Score (0 to 4 Scale; 0=None, 4=Very Severe)
The overall ocular discomfort will be assessed on a questionnaire using a 0 to 4 scale on which 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe.
Time frame: 6 month visit
Population: Efficacy analyses including the overall ocular discomfort score were planned for the intent-to-treat (ITT) population who are defined as all randomized patients. Ultimately, these analyses were not fully performed due to the early termination of the study and only six patients reaching the 6 month visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AGN-195263 | Overall Ocular Discomfort Score (0 to 4 Scale; 0=None, 4=Very Severe) | 1.66 Score on a scale | Standard Deviation 0.513 |
| Vehicle | Overall Ocular Discomfort Score (0 to 4 Scale; 0=None, 4=Very Severe) | 1.75 Score on a scale | Standard Deviation 0.204 |
Secondary
Change From Baseline in Tearfilm Break Up Time (TBUT)
For TBUT, the mean of 3 measurements of time in seconds will be computed at each visit for each eye. The mean value of the study eye will be used for analysis
Time frame: Baseline (day 1) to 6 month visit
Population: Efficacy analyses including the change from baseline in Tearfilm Break Up Time (TBUT) were planned. Ultimately, these analyses were not fully performed due to the early termination of the study and only six patients reaching the 6 month visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AGN-195263 | Change From Baseline in Tearfilm Break Up Time (TBUT) | 3.18 Seconds | Standard Deviation 0.284 |
| Vehicle | Change From Baseline in Tearfilm Break Up Time (TBUT) | 3.16 Seconds | Standard Deviation 0.286 |