Dry Eye Syndromes
Conditions
Brief summary
This study will evaluate the safety, tolerability and pharmacokinetics of two formulations of cyclosporine ophthalmic emulsion in healthy adults (parallel-group phase). The parallel-group phase will be followed by a paired-eye phase which will evaluate the safety and tolerability of two formulations of cyclosporine ophthalmic emulsion compared with cyclosporine ophthalmic emulsion (RESTASIS®) in patients with dry eye.
Interventions
DRUGcyclosporine ophthalmic emulsion Formulation A
One drop of cyclosporine ophthalmic emulsion Formulation A administered to each eye twice daily for 2 days and once in the morning of Day 3.
DRUGcyclosporine ophthalmic emulsion Formulation B
One drop of cyclosporine ophthalmic emulsion Formulation B administered to each eye twice daily for 2 days and once in the morning of Day 3.
DRUGcyclosporine ophthalmic emulsion Formulation A; cyclosporine ophthalmic emulsion 0.05%
One drop of cyclosporine ophthalmic emulsion Formulation A administered to one eye and one drop of cyclosporine ophthalmic emulsion 0.05% administered to the opposite eye, twice daily for 1 day.
DRUGcyclosporine ophthalmic emulsion Formulation B; cyclosporine ophthalmic emulsion 0.05%
One drop of cyclosporine ophthalmic emulsion Formulation B administered to one eye and one drop of cyclosporine ophthalmic emulsion 0.05% administered to the opposite eye, twice daily for 1 day.
DRUGcyclosporine ophthalmic emulsion Formulation A; cyclosporine ophthalmic emulsion Formulation B
One drop of cyclosporine ophthalmic emulsion Formulation A administered to one eye and one drop of cyclosporine ophthalmic emulsion Formulation B administered to the opposite eye, twice daily for 1 day.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Parallel-Group Phase: * Weigh at least 110 lbs * 18 to 45 years old Paired-Eye Phase: * Dry eye disease in both eyes
Exclusion criteria
Parallel-Group Phase: * Use of nicotine products, any medications, supplements or herbal products or consumption of grapefruit juice within 14 days or anticipated use during the study * Has donated blood within 90 days * Significant weight change (over 10 lbs) within 60 days * Previous use of RESTASIS® Parallel-Group and Paired-Eye Phases: * Anticipated wearing of contact lenses during the study or wearing of contact lenses within 14 days * Consumption of alcohol products within 72 hours Paired-Eye Phase: * Previous ocular surgery * Use of RESTASIS® within 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Day 1 | Concentration of cyclosporine measured in blood at Day 1 of the parallel-group phase (PGP). Blood samples were collected up to 3 hours post-dose and concentrations of cyclosporine were measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Reported Ocular Symptoms During the Parallel-Group Phase (PGP) | 3 Days | Number of subjects who reported ocular symptoms of any severity during the parallel-group phase (PGP) of the study. Subjects evaluated the presence and severity of ocular symptoms in each eye. The severity of each symptom (blurring, foreign body sensation, pain, burning/stinging, tearing, and itching) were recorded on a 5-point scale (0=none, +0.5=very mild,+1=mild, +2=moderate, and +3=severe). |
| Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Day 1 | Number of eyes with ocular symptoms of any severity, post-dose in the paired-eye phase (PEP) at Day 1. Subjects evaluated the presence and severity of ocular symptoms in each eye. The severity of each symptom (blurring, foreign body sensation, pain, burning/stinging, tearing, and itching) were recorded on a 5-point scale (0=none, +0.5=very mild, +1=mild, +2=moderate, and +3=severe). |
Countries
United States
Participant flow
Pre-assignment details
This study included a parallel-group phase (PGP) and a paired-eye phase (PEP). The paired-eye phase of the study began after the parallel-group phase completed. The parallel-group phase enrolled healthy volunteers and the paired-eye phase enrolled patients with dry eye symptoms.
Participants by arm
| Arm | Count |
|---|---|
| PGP: Cyclosporine Formulation A Parallel-Group Phase (PGP): cyclosporine ophthalmic emulsion Formulation A | 10 |
| PGP: Cyclosporine Formulation B PGP: cyclosporine ophthalmic emulsion Formulation B | 10 |
| PEP: Cyclosporine Formulation A and Cyclosporine 0.05% Paired-Eye Phase (PEP): cyclosporine ophthalmic emulsion Formulation A and cyclosporine ophthalmic emulsion 0.05% | 8 |
| PEP: Cyclosporine Formulation B and Cyclosporine 0.05% PEP: cyclosporine ophthalmic emulsion Formulation B and cyclosporine ophthalmic emulsion 0.05% | 8 |
| PEP: Cyclosporine Formulation A and Cyclosporine Formulation B PEP: cyclosporine ophthalmic emulsion Formulation A and cyclosporine ophthalmic emulsion Formulation B | 8 |
| Total | 44 |
Baseline characteristics
| Characteristic | PGP: Cyclosporine Formulation A | PGP: Cyclosporine Formulation B | PEP: Cyclosporine Formulation A and Cyclosporine 0.05% | PEP: Cyclosporine Formulation B and Cyclosporine 0.05% | PEP: Cyclosporine Formulation A and Cyclosporine Formulation B | Total |
|---|---|---|---|---|---|---|
| Age, Customized 18 to 30 years | 8 participants | 8 participants | 1 participants | 1 participants | 1 participants | 19 participants |
| Age, Customized > 30 to 40 years | 2 participants | 2 participants | 0 participants | 1 participants | 0 participants | 5 participants |
| Age, Customized > 40 years | 0 participants | 0 participants | 7 participants | 6 participants | 7 participants | 20 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 5 Participants | 5 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 3 Participants | 3 Participants | 0 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 10 | 2 / 10 | 5 / 8 | 8 / 8 | 8 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP)
Concentration of cyclosporine measured in blood at Day 1 of the parallel-group phase (PGP). Blood samples were collected up to 3 hours post-dose and concentrations of cyclosporine were measured.
Time frame: Day 1
Population: Safety Population: All randomized subjects who were treated with at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyclosporine Formulation A | Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Time = pre-dose | NA Nanogram/milliliter (ng/mL) |
| Cyclosporine Formulation A | Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Time = 0.5 hours | NA Nanogram/milliliter (ng/mL) |
| Cyclosporine Formulation A | Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Time = 1 hour | NA Nanogram/milliliter (ng/mL) |
| Cyclosporine Formulation A | Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Time = 3 hours | NA Nanogram/milliliter (ng/mL) |
| Cyclosporine Formulation B | Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Time = 3 hours | NA Nanogram/milliliter (ng/mL) |
| Cyclosporine Formulation B | Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Time = pre-dose | NA Nanogram/milliliter (ng/mL) |
| Cyclosporine Formulation B | Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Time = 1 hour | NA Nanogram/milliliter (ng/mL) |
| Cyclosporine Formulation B | Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Time = 0.5 hours | NA Nanogram/milliliter (ng/mL) |
Secondary
Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1
Number of eyes with ocular symptoms of any severity, post-dose in the paired-eye phase (PEP) at Day 1. Subjects evaluated the presence and severity of ocular symptoms in each eye. The severity of each symptom (blurring, foreign body sensation, pain, burning/stinging, tearing, and itching) were recorded on a 5-point scale (0=none, +0.5=very mild, +1=mild, +2=moderate, and +3=severe).
Time frame: Day 1
Population: Per Protocol: All randomized subjects who received their assigned study medication and closely followed the protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyclosporine Formulation A | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Blurring | 2 Number of Eyes |
| Cyclosporine Formulation A | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Pain | 0 Number of Eyes |
| Cyclosporine Formulation A | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Itching | 0 Number of Eyes |
| Cyclosporine Formulation A | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Tearing | 1 Number of Eyes |
| Cyclosporine Formulation A | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Foreign Body Sensation | 0 Number of Eyes |
| Cyclosporine Formulation A | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Burning/Stinging | 3 Number of Eyes |
| Cyclosporine Formulation B | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Itching | 0 Number of Eyes |
| Cyclosporine Formulation B | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Blurring | 1 Number of Eyes |
| Cyclosporine Formulation B | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Tearing | 2 Number of Eyes |
| Cyclosporine Formulation B | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Foreign Body Sensation | 0 Number of Eyes |
| Cyclosporine Formulation B | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Pain | 1 Number of Eyes |
| Cyclosporine Formulation B | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Burning/Stinging | 2 Number of Eyes |
| Cyclosporine 0.05% | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Burning/Stinging | 2 Number of Eyes |
| Cyclosporine 0.05% | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Pain | 0 Number of Eyes |
| Cyclosporine 0.05% | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Foreign Body Sensation | 0 Number of Eyes |
| Cyclosporine 0.05% | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Blurring | 1 Number of Eyes |
| Cyclosporine 0.05% | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Itching | 0 Number of Eyes |
| Cyclosporine 0.05% | Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Tearing | 3 Number of Eyes |
Secondary
Number of Subjects Who Reported Ocular Symptoms During the Parallel-Group Phase (PGP)
Number of subjects who reported ocular symptoms of any severity during the parallel-group phase (PGP) of the study. Subjects evaluated the presence and severity of ocular symptoms in each eye. The severity of each symptom (blurring, foreign body sensation, pain, burning/stinging, tearing, and itching) were recorded on a 5-point scale (0=none, +0.5=very mild,+1=mild, +2=moderate, and +3=severe).
Time frame: 3 Days
Population: Per Protocol: All randomized subjects who received their assigned study medication and closely followed the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclosporine Formulation A | Number of Subjects Who Reported Ocular Symptoms During the Parallel-Group Phase (PGP) | 3 Number of Subjects |
| Cyclosporine Formulation B | Number of Subjects Who Reported Ocular Symptoms During the Parallel-Group Phase (PGP) | 1 Number of Subjects |