Dry Eye Disease
Conditions
Brief summary
The purpose of this Phase 2a study is to assess changes in tear volume by the non-invasive techniques Ultra High Resolution Optical Coherence Tomography (UHR-OCT) following the administration of P-321 Ophthalmic Solution or Placebo in subjects with tear deficient dry eye disease.
Detailed description
This is a single-center, randomized, cross-over placebo controlled study to evaluate the changes in tear volume by P-321 Ophthalmic Solution and Placebo. The study will enroll subjects with tear deficient dry eye disease to receive sequentially one of two treatment sequences: P-321 Ophthalmic Solution then Placebo or Placebo then P-321. The study will consist of two Phases: In each Phase, subjects will be treated with P-321 Ophthalmic Solution under the same study design. Approximately twenty-four eligible subjects will complete the study with approximately 8 subjects participating in Phase 1 and the remainder of the 24 subjects participating in the phase 2. Decisions on the dose to be used in Phase 2 will be made based on Phase 1 data. The study will consist of three study visits: a Screening Visit (Visit 1), and two treatment visits (Visit 2 and Visit 3). The primary and secondary outcome measures will be assessed at each treatment visit. Safety assessments include adverse events (AEs).
Interventions
Sponsors
Parion Sciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent 2. Male or female subjects aged 18 to 80 years 3. Have a history of predominantly tear-deficient dry eye of mild to moderate severity, supported by a previous clinical diagnosis 4. Have normal lid anatomy 5. Subjects must: 1. Remain on current medications for the duration of the study and have been on the current medication regimen at least during the past 28 days
Exclusion criteria
1. Have undergone refractive eye surgery in either eye during the past 12 months 2. Have undergone uncomplicated cataract surgery in either eye during the past 3 months 3. Have undergone previous eyelid surgery in either eye (External blepharoplasty, not resulting in exposure or abnormal blinking is allowed) 4. Have undergone botulinum toxin (BotoxTh1 or equivalent) injection in the periocular area within 3 months prior to Visit 1 5. Subjects that have a systemic, multi-organ disease requiring active medical or surgical treatment are excluded with the exception of subjects with SS or GVHD 6. Have punctal plugs, punctal occlusion, history of nasolacrimal duct obstruction or wear scleral lens. 7. Past or present exposure keratopathy, neurotrophic keratopathy, lagophthalmos, or trichiasis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Tear Meniscus Volume Following the Administration of P-321 Ophthalmic Solution or Placebo | Pre-dose and up to six hours after dose | Tear meniscus volume, from measurements of tear meniscus area by UHR-OCT and the length of the eyelid was estimated over time (0 to 6 hours) following administration of placebo or P-321 Ophthalmic Solution. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lower Tear Meniscus Height as Measured by the Keratograph 5M | Pre-dose and up to six hours after dose | Tear meniscus height of the inferior eyelid was measured with the Keratograph 5M over time (0 to 6 hours) following the administration of placebo or P-321 Ophthalmic Solution |
| Comparison of Lower Tear Meniscus Height Measurements Between UHR-OCT and Keratograph 5M | Pre-dose and up to six hours after dose | Tear meniscus height of the inferior eyelid was measured by UHR-OCT and Keratograph 5M over time (0 to 6 hours) following the administration of placebo or P-321 Ophthalmic Solution |
| Adverse Events | 2 or 7 hours | Number of patients experiencing adverse events comparing P-321 to placebo |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| P-321 Ophthalmic Solution Then Placebo Comparator At Visit 2 0.017% P-321 Ophthalmic Solution will be administered to approximately 8 patients in Phase I and either 0.05% P-321 Ophthalmic Solution or 0.01% P-321 Ophthalmic Solution or additional 0.017% P-321 Ophthalmic Solution will be administered to approximately 16 patients in Phase II P-321 Ophthalmic Solution
At Visit 3 Placebo comparator will be administered to approximately 8 patients in Phase I and approximately 16 patients in Phase II | 1 |
| Placebo Comparator Then P-321 Ophthalmic Solution At Visit 2 Placebo comparator will be administered to approximately 8 patients in Phase I and approximately 16 patients in Phase II
At Visit 3 0.017% P-321 Ophthalmic Solution will be administered to approximately 8 patients in Phase I and either 0.05% P-321 Ophthalmic Solution or 0.01% P-321 Ophthalmic Solution or additional 0.017% P-321 Ophthalmic Solution will be administered to approximately 16 patients in Phase II P-321 Ophthalmic Solution | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | P-321 Ophthalmic Solution Then Placebo Comparator | Placebo Comparator Then P-321 Ophthalmic Solution | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 1 participants | — | 1 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Change in Total Tear Meniscus Volume Following the Administration of P-321 Ophthalmic Solution or Placebo
Tear meniscus volume, from measurements of tear meniscus area by UHR-OCT and the length of the eyelid was estimated over time (0 to 6 hours) following administration of placebo or P-321 Ophthalmic Solution.
Time frame: Pre-dose and up to six hours after dose
Population: One subject enrolled in the study. Subject received both study treatments (a single instillation of 0.017% P-321 Ophthalmic Solution in both eyes and a single instillation of Placebo in both eyes).~Study was terminated, raw data obtained. Processing of data was not conducted to obtain primary and secondary outcomes, therefore none reported.
Secondary
Adverse Events
Number of patients experiencing adverse events comparing P-321 to placebo
Time frame: 2 or 7 hours
Population: One subject enrolled in the study. Subject received both study treatments (a single instillation of 0.017% P-321 Ophthalmic Solution in both eyes and a single instillation of Placebo in both eyes).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| P-321 Ophthalmic Solution Then Placebo Comparator | Adverse Events | 0 Participants |
| Placebo Comparator Then P-321 Ophthalmic Solution | Adverse Events | 0 Participants |
Secondary
Comparison of Lower Tear Meniscus Height Measurements Between UHR-OCT and Keratograph 5M
Tear meniscus height of the inferior eyelid was measured by UHR-OCT and Keratograph 5M over time (0 to 6 hours) following the administration of placebo or P-321 Ophthalmic Solution
Time frame: Pre-dose and up to six hours after dose
Population: One subject enrolled in the study. Subject received both study treatments (a single instillation of 0.017% P-321 Ophthalmic Solution in both eyes and a single instillation of Placebo in both eyes).~Study was terminated, raw data obtained. Processing of data was not conducted to obtain primary and secondary outcomes, therefore none reported.
Secondary
Lower Tear Meniscus Height as Measured by the Keratograph 5M
Tear meniscus height of the inferior eyelid was measured with the Keratograph 5M over time (0 to 6 hours) following the administration of placebo or P-321 Ophthalmic Solution
Time frame: Pre-dose and up to six hours after dose
Population: One subject enrolled in the study. Subject received both study treatments (a single instillation of 0.017% P-321 Ophthalmic Solution in both eyes and a single instillation of Placebo in both eyes).~Study was terminated, raw data obtained. Processing of data was not conducted to obtain primary and secondary outcomes, therefore none reported.