Blepharoptosis
Conditions
Brief summary
Phase 3 study to evaluate the safety and efficacy of treatment with RVL-1201 compared to placebo for treatment of blepharoptosis. Eligible subjects will be randomized to one of 2 treatment arms.
Interventions
DRUGRVL-1201
RVL-1201 ophthalmic solution 0.1%
OTHERVehicle ophthalmic solution
Vehicle placebo ophthalmic solution
Sponsors
RVL Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
9 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or Female 9 years of age or older 2. Females must not be pregnant or planning to get pregnant and must use acceptable form of contraception 3. Must be able to self-administer study medication 4. Must be able to understand and sign an informed consent form. For minor subjects, the subject's parent or legal guardian must provide permission by signing an ICF on behalf of the subject and the subject should provide assent.
Exclusion criteria
1. Congenital ptosis 2. Horner syndrome 3. Myasthenia gravis 4. Mechanical ptosis 5. Previous ptosis surgery 6. Resting heart rate outside the normal range 7. Hypertension with resting diastolic blood pressure 8. Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Number of Points Seen on the Leicester Peripheral Field Test (LPFT) in RVL-1201 Group vs. Vehicle Group | Mean change from Baseline (Day 1, Hour 0) compared with Day 1, (Hour 6), and Day 14 (Hour 2) | LPFT Total Score is the number of points seen in the top 4 rows on the LPFT. Possible scores range from 0 (no points seen) to 35 (all points seen). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Baseline Day 1 (Hour 0) and Day 1, Day 14, and Day 42 | The Marginal Reflex Distance (MRD) is the distance from the center pupillary light reflex to the central margin of the upper eyelid. The MRD is measured from an external photograph using a handheld caliper and a millimeter ruler label placed on the subject's forehead as a measurement legend. |
Countries
United States
Participant flow
Recruitment details
Planned sample size was approximately 156 subjects, 104 subjects in the RVL-1201 group, and 52 in the Vehicle group, to be enrolled at approximately 30 clinical sites in the U.S.
Participants by arm
| Arm | Count |
|---|---|
| RVL-1201 Ophthalmic Solution 0.1% RVL-1201 (oxymetazoline hydrochloride) ophthalmic solution 0.1% One drop each eye QD in the morning | 109 |
| Vehicle Ophthalmic Solution Vehicle placebo ophthalmic Solution One drop each eye QD in the morning | 55 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | RVL-1201 Ophthalmic Solution 0.1% | Vehicle Ophthalmic Solution | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 63 Participants | 32 Participants | 95 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 22 Participants | 68 Participants |
| Age, Continuous | 63.6 years STANDARD_DEVIATION 14.31 | 63.3 years STANDARD_DEVIATION 16.51 | 63.5 years STANDARD_DEVIATION 15.03 |
| Age, Customized | 67.0 years | 67.0 years | 67.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 6 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 49 Participants | 145 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Iris Color OD (right eye) OD-Blue | 40 Participants | 18 Participants | 58 Participants |
| Iris Color OD (right eye) OD-Brown | 46 Participants | 18 Participants | 64 Participants |
| Iris Color OD (right eye) OD-Green | 7 Participants | 3 Participants | 10 Participants |
| Iris Color OD (right eye) OD-Grey | 1 Participants | 1 Participants | 2 Participants |
| Iris Color OD (right eye) OD-Hazel | 15 Participants | 15 Participants | 30 Participants |
| Iris Color OS (left eye) OS-Blue | 40 Participants | 18 Participants | 58 Participants |
| Iris Color OS (left eye) OS-Brown | 47 Participants | 18 Participants | 65 Participants |
| Iris Color OS (left eye) OS-Green | 6 Participants | 3 Participants | 9 Participants |
| Iris Color OS (left eye) OS-Grey | 1 Participants | 1 Participants | 2 Participants |
| Iris Color OS (left eye) OS-Hazel | 15 Participants | 15 Participants | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 99 Participants | 50 Participants | 149 Participants |
| Region of Enrollment United States | 109 participants | 55 participants | 164 participants |
| Sex: Female, Male Female | 77 Participants | 39 Participants | 116 Participants |
| Sex: Female, Male Male | 32 Participants | 16 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 109 | 0 / 55 |
| other Total, other adverse events | 13 / 109 | 8 / 55 |
| serious Total, serious adverse events | 1 / 109 | 1 / 55 |
Outcome results
Primary
Mean Change in Number of Points Seen on the Leicester Peripheral Field Test (LPFT) in RVL-1201 Group vs. Vehicle Group
LPFT Total Score is the number of points seen in the top 4 rows on the LPFT. Possible scores range from 0 (no points seen) to 35 (all points seen).
Time frame: Mean change from Baseline (Day 1, Hour 0) compared with Day 1, (Hour 6), and Day 14 (Hour 2)
Population: Intent-to-Treat (ITT) population: randomized who received at least one dose. Per-Protocol Population (PPP): ITT population with no major protocol deviations (eleven subjects were excluded). ITT analysis was conducted for the primary endpoint, with Last Observation Carried Forward (LOCF) for missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change in Number of Points Seen on the Leicester Peripheral Field Test (LPFT) in RVL-1201 Group vs. Vehicle Group | Mean change from baseline LPFT-Day 1 Hour 6 | 6.3 Points seen | Standard Deviation 6.72 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change in Number of Points Seen on the Leicester Peripheral Field Test (LPFT) in RVL-1201 Group vs. Vehicle Group | Mean change from baseline LPFT-Day 14 Hour 2 | 7.7 Points seen | Standard Deviation 6.41 |
| Vehicle Ophthalmic Solution | Mean Change in Number of Points Seen on the Leicester Peripheral Field Test (LPFT) in RVL-1201 Group vs. Vehicle Group | Mean change from baseline LPFT-Day 1 Hour 6 | 2.1 Points seen | Standard Deviation 4.28 |
| Vehicle Ophthalmic Solution | Mean Change in Number of Points Seen on the Leicester Peripheral Field Test (LPFT) in RVL-1201 Group vs. Vehicle Group | Mean change from baseline LPFT-Day 14 Hour 2 | 2.4 Points seen | Standard Deviation 5.26 |
Comparison: A two group t-test with a 0.05 two-sided significance level had 90% power to detect a difference in LPFT means of 3.50 assuming that the common standard deviation was 6.0, when the sample sizes in the 2 groups were 94 and 47, respectively (a total sample size of 141).p-value: <0.0001ANCOVA
Secondary
Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye
The Marginal Reflex Distance (MRD) is the distance from the center pupillary light reflex to the central margin of the upper eyelid. The MRD is measured from an external photograph using a handheld caliper and a millimeter ruler label placed on the subject's forehead as a measurement legend.
Time frame: Baseline Day 1 (Hour 0) and Day 1, Day 14, and Day 42
Population: Intent-to-Treat (ITT) population: randomized who received at least one dose. Per-Protocol Population (PPP): ITT population with no major protocol deviations (eleven subjects were excluded). ITT analysis was conducted for the primary endpoint, with Last Observation Carried Forward (LOCF) for missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 1, Minute 5 | 0.59 Millimeters (mm) | Standard Deviation 0.721 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 1, Minute 15 | 0.93 Millimeters (mm) | Standard Deviation 0.811 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 1, Hour 2 | 1.05 Millimeters (mm) | Standard Deviation 0.903 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 1, Hour 6 | 0.98 Millimeters (mm) | Standard Deviation 0.867 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 14, Minute 5 | 0.77 Millimeters (mm) | Standard Deviation 0.853 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 14, Minute 15 | 1.11 Millimeters (mm) | Standard Deviation 0.922 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 14, Hour 2 | 1.22 Millimeters (mm) | Standard Deviation 0.926 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 14, Hour 6 | 1.06 Millimeters (mm) | Standard Deviation 0.902 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 42, Minute 5 | 0.86 Millimeters (mm) | Standard Deviation 0.849 |
| RVL-1201 Ophthalmic Solution 0.1% | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 42, Minute 15 | 1.04 Millimeters (mm) | Standard Deviation 0.912 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 14, Hour 6 | 0.47 Millimeters (mm) | Standard Deviation 0.737 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 1, Minute 5 | 0.20 Millimeters (mm) | Standard Deviation 0.571 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 14, Minute 15 | 0.41 Millimeters (mm) | Standard Deviation 0.833 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 1, Minute 15 | 0.32 Millimeters (mm) | Standard Deviation 0.641 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 42, Minute 15 | 0.47 Millimeters (mm) | Standard Deviation 0.926 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 1, Hour 2 | 0.33 Millimeters (mm) | Standard Deviation 0.555 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 14, Hour 2 | 0.43 Millimeters (mm) | Standard Deviation 0.734 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 1, Hour 6 | 0.35 Millimeters (mm) | Standard Deviation 0.567 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 42, Minute 5 | 0.42 Millimeters (mm) | Standard Deviation 0.799 |
| Vehicle Ophthalmic Solution | Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye | Day 14, Minute 5 | 0.42 Millimeters (mm) | Standard Deviation 0.775 |
Comparison: A two group t-test with a 0.05 two-sided significance level had 90% power to detect a difference in LPFT means of 3.50 assuming that the common standard deviation was 6.0, when the sample sizes in the 2 groups were 94 and 47, respectively (a total sample size of 141).p-value: <0.0151ANCOVA