Back to resultsSafety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis
Primary Purpose
Blepharoptosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RVL-1201
RVL-1201 Vehicle Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Blepharoptosis focused on measuring Blepharoptosis, Ptosis
Eligibility Criteria
Inclusion Criteria:
- Adult male or female subjects 18 years of age and older.
Presence of all of the following at Screening:
- Loss on HVF 36-point ptosis protocol test of ≥ 8 points in points not seen at or above 10° from fixation in the superior visual field; AND
- Marginal reflex distance (MRD), the distance from the central pupillary light reflex to the upper lid margin, of ≤ 2.5 mm in the same eye as Inclusion Criterion #2a; AND
- Corrected Snellen visual acuity (VA) of 20/40 or better (refraction must be within 6 months of Visit 1) in the same eye as Inclusion Criteria #2a and #2b.
- No contraindications for treatment of both eyes as specified in Exclusion Criteria #1-14.
- Female subjects must be 1-year postmenopausal, surgically sterilized, or women of childbearing potential with a negative urine pregnancy test at Visit 1. Women of childbearing potential must use an acceptable form of contraception throughout the study.
- Provide informed consent prior to undergoing any study-related procedures.
Exclusion Criteria:
In either eye:
- Congenital ptosis
- Pseudoptosis
- Horner syndrome
- Marcus Gunn jaw-winking syndrome
- Myasthenia gravis
- Mechanical ptosis, including ptosis due to orbital or lid tumor, cicatricial processes affecting the movements of the upper lid, and enophthalmos
- Dermatochalasis as the sole cause of the signs of ptosis
- Previous ptosis surgery
- Lid position affected by lid or conjunctival scarring
- Current use of prescribed dry eye medication or punctal plugs; artificial tears are allowed
- Visual field loss from any cause other than ptosis
- Inability to fixate on the central fixation target of the HVF
- Primary open-angle glaucoma or ocular hypertension, intraocular pressure (IOP) > 24 mm Hg, or current use/use within 1 month prior to Visit 1 of any antiglaucoma medications.
- History of closed/narrow angle glaucoma (unless patent peripheral iridotomy has been performed > 3 months prior to Visit 1 and IOP < 20 mm Hg) or normal-tension glaucoma
- Use of over-the-counter vasoconstrictor/decongestant eye medication (eg, Visine® L.R.®) or any α-adrenergic agonist (including OTC products) at any time during the study
Contact lens wear during the study period
General:
- Resting heart rate (HR) outside the normal range (60 - 100 beats per minute)
- Hypertension diastolic blood pressure (BP) > 105 mm Hg
- Use of monoamine oxidase inhibitors (MAOIs; eg, isocarboxazid, phenelzine, tranylcypromine) within 14 days prior to Visit 1 or during the study
- Use of beta blockers (eg, propranolol, metoprolol, labetalol) within 14 days prior to Visit 1 or during the study
- Use of maprotiline, selective serotonin reuptake inhibitors ([SSRIs] eg, citalopram, escitalopram, paroxetine, fluoxetine, fluvoxamine, sertraline) or tricyclic antidepressants (eg, amitriptyline, doxepin, nortriptyline, amoxapine, clomipramine, desipramine, imipramine, protriptyline, trimipramine) at any time during the study
- A history of myocardial infarction, angina, arrhythmia, or irregular pulse
- Advanced arteriosclerotic disease
- History of thyroid disease
- Insulin-dependent diabetes or diabetes requiring oral hypoglycemic drugs; diet-controlled diabetes is allowed
- Pregnancy or lactation
- Diagnosed benign prostatic hypertrophy requiring medicinal therapy.
- History of contact or systemic allergic reaction to oxymetazoline or other sympathomimetic drugs (eg, phenylephrine, pseudoephedrine, ephedrine, phenylpropanolamine, fepradinol, or methoxamine)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
RVL-1201 once daily
RVL-1201 twice daily
RVL-1201 vehicle (placebo)
Arm Description
RVL-1201 0.1% ophthalmic solution dosed one full drop per eye in the morning; one full drop of vehicle (placebo) per eye approximately 8 hours after the morning dose
RVL-1201 0.1% ophthalmic solution dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose
RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose
Outcomes
Primary Outcome Measures
Humphrey Visual Field
The mean change from baseline (Day 0, Hour 0) in number of points seen on the HVF 36-point ptosis protocol test according to a pre-planned hierarchical analysis as follows:
Hour 6 on Visit 4 (Day 13) for the BID regimen versus vehicle
Hour 6 on Visit 4 (Day 13) for the QD regimen versus vehicle
Hour 2 on Visit 4 (Day 13) for the BID regimen versus vehicle
Hour 2 on Visit 4 (Day 13) for the QD regimen versus vehicle
Testing was performed using a Humphrey perimeter at a grid of 36 points confined to the superior hemifield extending 55° to either side of fixation and 45° superior to fixation. Testing was accomplished in the standard fashion using a varying 4-mm2 or 5-mm2 stimulus to determine the visual sensitivity for each grid point in the field (Riemann et al, 2000). A 4-mm2 stimulus was acceptable, but a 5-mm2 stimulus was preferred, if available.
Secondary Outcome Measures
Marginal Reflex Distance
Change from baseline in MRD by regimen against placebo and between regimen.
The distance from the pupillary light reflex to the central margin of the upper eyelid is the MRD. The MRD will be measured from the external photograph using calipers and the millimeter ruler as the legend.
Palpebral Fissure Distance Measurement
Change from baseline in PFD by regimen against placebo and between regimen.
The PFD is the distance from the upper lid margin to the lower lid margin measured through the central visual axis. It will be measured from the external photograph using handheld calipers and the millimeter ruler as the legend.
Contrast Sensitivity
Change from baseline in CS by regimen against placebo and between regimen.
The Pelli-Robson contrast sensitivity chart will be used at a distance of 1 meter. The subject was instructed to begin reading the letters at the top of the chart and to continue reading across and down the chart. Testing was discontinued when 2 of 3 letters were named incorrectly. The test was scored using the letter-by-letter method where a value of 0.05 log CS is given per correct letter (Haymes et al, 2006).
Corrected Snellen Visual Acuity
Change from baseline in VA by regimen against placebo and between regimen.
Corrected Snellen VA measurement was performed with the Snellen eye chart using subjects current corrective lens prescription at a distance equivalent to 20 feet (6 meters).
Full Information
NCT ID
NCT01848041
First Posted
May 3, 2013
Last Updated
November 23, 2021
Sponsor
RVL Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01848041
Brief Title
Safety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis
Official Title
A Randomized, Double-Masked, Placebo-Controlled Phase 1/2a Study of the Efficacy and Safety of Two Dosing Regimens of RVL-1201 in the Treatment of Acquired Blepharoptosis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
February 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RVL Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an exploratory, proof of concept study to evaluate the safety and efficacy of RVL-1201 dosed once or twice daily for 14 days compared to a placebo (vehicle) control in patients with ptosis.
Detailed Description
This is an exploratory, proof-of-concept study. The objectives include establishing the efficacy and duration of effect of once daily (QD) or twice daily (BID) administration of RVL-1201 and the safety profile following 14 days of treatment in 72 subjects (24 per arm) with acquired blepharoptosis.
Efficacy will be assessed at each treatment visit by the Humphrey Visual Field 36-point ptosis protocol test, photographic measurement of marginal reflex distance, palpebral fissure distance and contrast sensitivity in the study eye only and Visual Acuity assessment in both eyes.
Safety assessments will include slit lamp examination/corneal fluorescein staining, pupil size measurement, ophthalmoscopy/ fundus examination, tonometry, visual acuity; urine pregnancy test (for women of childbearing potential only), vital signs (Heart Rate/Blood Pressure); and collection of adverse events. Subject rating of study medication comfort and assessment of ongoing tolerability will also be obtained.
Primary efficacy endpoint is the mean increase from baseline in points seen on the HVF 36-point ptosis protocol test at various timepoints according to a hierarchical analysis.
Analysis of exploratory endpoints will provide characterization of the efficacy and duration of effect of RVL-1201 with a variety of efficacy measures, as well as the potential additional effect of BID over QD dosing and safety profile of BID administration of RVL-1201. Exploratory endpoints will be analyzed by each regimen against placebo and between regimens and will include:
The change from baseline in HVF, MRD, PFD, VA, and CS.
The change from baseline in BP/HR
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blepharoptosis
Keywords
Blepharoptosis, Ptosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RVL-1201 once daily
Arm Type
Experimental
Arm Description
RVL-1201 0.1% ophthalmic solution dosed one full drop per eye in the morning; one full drop of vehicle (placebo) per eye approximately 8 hours after the morning dose
Arm Title
RVL-1201 twice daily
Arm Type
Experimental
Arm Description
RVL-1201 0.1% ophthalmic solution dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose
Arm Title
RVL-1201 vehicle (placebo)
Arm Type
Placebo Comparator
Arm Description
RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose
Intervention Type
Drug
Intervention Name(s)
RVL-1201
Other Intervention Name(s)
Oxymetazoline Hydrochloride Ophthalmic Solution 0.1%
Intervention Description
RVL-1201 0.1% Ophthalmic Solution
Intervention Type
Drug
Intervention Name(s)
RVL-1201 Vehicle Placebo
Other Intervention Name(s)
RVL-1201 Ophthalmic Solution 0.1% Placebo
Intervention Description
RVL-1201 Vehicle Placebo
Primary Outcome Measure Information:
Title
Humphrey Visual Field
Description
The mean change from baseline (Day 0, Hour 0) in number of points seen on the HVF 36-point ptosis protocol test according to a pre-planned hierarchical analysis as follows:
Hour 6 on Visit 4 (Day 13) for the BID regimen versus vehicle
Hour 6 on Visit 4 (Day 13) for the QD regimen versus vehicle
Hour 2 on Visit 4 (Day 13) for the BID regimen versus vehicle
Hour 2 on Visit 4 (Day 13) for the QD regimen versus vehicle
Testing was performed using a Humphrey perimeter at a grid of 36 points confined to the superior hemifield extending 55° to either side of fixation and 45° superior to fixation. Testing was accomplished in the standard fashion using a varying 4-mm2 or 5-mm2 stimulus to determine the visual sensitivity for each grid point in the field (Riemann et al, 2000). A 4-mm2 stimulus was acceptable, but a 5-mm2 stimulus was preferred, if available.
Time Frame
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
Secondary Outcome Measure Information:
Title
Marginal Reflex Distance
Description
Change from baseline in MRD by regimen against placebo and between regimen.
The distance from the pupillary light reflex to the central margin of the upper eyelid is the MRD. The MRD will be measured from the external photograph using calipers and the millimeter ruler as the legend.
Time Frame
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
Title
Palpebral Fissure Distance Measurement
Description
Change from baseline in PFD by regimen against placebo and between regimen.
The PFD is the distance from the upper lid margin to the lower lid margin measured through the central visual axis. It will be measured from the external photograph using handheld calipers and the millimeter ruler as the legend.
Time Frame
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
Title
Contrast Sensitivity
Description
Change from baseline in CS by regimen against placebo and between regimen.
The Pelli-Robson contrast sensitivity chart will be used at a distance of 1 meter. The subject was instructed to begin reading the letters at the top of the chart and to continue reading across and down the chart. Testing was discontinued when 2 of 3 letters were named incorrectly. The test was scored using the letter-by-letter method where a value of 0.05 log CS is given per correct letter (Haymes et al, 2006).
Time Frame
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
Title
Corrected Snellen Visual Acuity
Description
Change from baseline in VA by regimen against placebo and between regimen.
Corrected Snellen VA measurement was performed with the Snellen eye chart using subjects current corrective lens prescription at a distance equivalent to 20 feet (6 meters).
Time Frame
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult male or female subjects 18 years of age and older.
Presence of all of the following at Screening:
Loss on HVF 36-point ptosis protocol test of ≥ 8 points in points not seen at or above 10° from fixation in the superior visual field; AND
Marginal reflex distance (MRD), the distance from the central pupillary light reflex to the upper lid margin, of ≤ 2.5 mm in the same eye as Inclusion Criterion #2a; AND
Corrected Snellen visual acuity (VA) of 20/40 or better (refraction must be within 6 months of Visit 1) in the same eye as Inclusion Criteria #2a and #2b.
No contraindications for treatment of both eyes as specified in Exclusion Criteria #1-14.
Female subjects must be 1-year postmenopausal, surgically sterilized, or women of childbearing potential with a negative urine pregnancy test at Visit 1. Women of childbearing potential must use an acceptable form of contraception throughout the study.
Provide informed consent prior to undergoing any study-related procedures.
Exclusion Criteria:
In either eye:
Congenital ptosis
Pseudoptosis
Horner syndrome
Marcus Gunn jaw-winking syndrome
Myasthenia gravis
Mechanical ptosis, including ptosis due to orbital or lid tumor, cicatricial processes affecting the movements of the upper lid, and enophthalmos
Dermatochalasis as the sole cause of the signs of ptosis
Previous ptosis surgery
Lid position affected by lid or conjunctival scarring
Current use of prescribed dry eye medication or punctal plugs; artificial tears are allowed
Visual field loss from any cause other than ptosis
Inability to fixate on the central fixation target of the HVF
Primary open-angle glaucoma or ocular hypertension, intraocular pressure (IOP) > 24 mm Hg, or current use/use within 1 month prior to Visit 1 of any antiglaucoma medications.
History of closed/narrow angle glaucoma (unless patent peripheral iridotomy has been performed > 3 months prior to Visit 1 and IOP < 20 mm Hg) or normal-tension glaucoma
Use of over-the-counter vasoconstrictor/decongestant eye medication (eg, Visine® L.R.®) or any α-adrenergic agonist (including OTC products) at any time during the study
Contact lens wear during the study period
General:
Resting heart rate (HR) outside the normal range (60 - 100 beats per minute)
Hypertension diastolic blood pressure (BP) > 105 mm Hg
Use of monoamine oxidase inhibitors (MAOIs; eg, isocarboxazid, phenelzine, tranylcypromine) within 14 days prior to Visit 1 or during the study
Use of beta blockers (eg, propranolol, metoprolol, labetalol) within 14 days prior to Visit 1 or during the study
Use of maprotiline, selective serotonin reuptake inhibitors ([SSRIs] eg, citalopram, escitalopram, paroxetine, fluoxetine, fluvoxamine, sertraline) or tricyclic antidepressants (eg, amitriptyline, doxepin, nortriptyline, amoxapine, clomipramine, desipramine, imipramine, protriptyline, trimipramine) at any time during the study
A history of myocardial infarction, angina, arrhythmia, or irregular pulse
Advanced arteriosclerotic disease
History of thyroid disease
Insulin-dependent diabetes or diabetes requiring oral hypoglycemic drugs; diet-controlled diabetes is allowed
Pregnancy or lactation
Diagnosed benign prostatic hypertrophy requiring medicinal therapy.
History of contact or systemic allergic reaction to oxymetazoline or other sympathomimetic drugs (eg, phenylephrine, pseudoephedrine, ephedrine, phenylpropanolamine, fepradinol, or methoxamine)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chuck Slonim, MD
Organizational Affiliation
Oculos Clinical Research
Official's Role
Principal Investigator
Facility Information:
City
Morrow
State/Province
Georgia
ZIP/Postal Code
30260
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis
We'll reach out to this number within 24 hrs