Safety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis

• Sponsor: RVL Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01848041
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 3
• Duration (Months): 9.1
• Patients Per Site Per Month: 5.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Blepharoptosis	Drug: RVL-1201; Drug: RVL-1201 Vehicle Placebo	Phase 1/Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: May 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RVL-1201 once daily 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	Drug: RVL-1201; RVL-1201 0.1% Ophthalmic Solution; Other Names: Oxymetazoline Hydrochloride Ophthalmic Solution 0.1%
Experimental: RVL-1201 twice daily RVL-1201 0.1% ophthalmic solution dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose	Drug: RVL-1201; RVL-1201 0.1% Ophthalmic Solution; Other Names: Oxymetazoline Hydrochloride Ophthalmic Solution 0.1%
Placebo Comparator: RVL-1201 vehicle (placebo) RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose	Drug: RVL-1201 Vehicle Placebo; RVL-1201 Vehicle Placebo; Other Names: RVL-1201 Ophthalmic Solution 0.1% Placebo

Outcome Measures

Primary Outcome Measures

1. Humphrey Visual Field [Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)]

   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

1. Marginal Reflex Distance [Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)]

   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.

2. Palpebral Fissure Distance Measurement [Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)]

   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.

3. Contrast Sensitivity [Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)]

   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).

4. Corrected Snellen Visual Acuity [Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult male or female subjects 18 years of age and older.

2. Presence of all of the following at Screening:

3. 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

4. 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

5. 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.

6. No contraindications for treatment of both eyes as specified in Exclusion Criteria #1-14.

7. 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.

8. Provide informed consent prior to undergoing any study-related procedures.

Exclusion Criteria:

In either eye:

1. Congenital ptosis

2. Pseudoptosis

3. Horner syndrome

4. Marcus Gunn jaw-winking syndrome

5. Myasthenia gravis

6. Mechanical ptosis, including ptosis due to orbital or lid tumor, cicatricial processes affecting the movements of the upper lid, and enophthalmos

7. Dermatochalasis as the sole cause of the signs of ptosis

8. Previous ptosis surgery

9. Lid position affected by lid or conjunctival scarring

10. Current use of prescribed dry eye medication or punctal plugs; artificial tears are allowed

11. Visual field loss from any cause other than ptosis

12. Inability to fixate on the central fixation target of the HVF

13. 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.

14. 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

15. 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

16. Contact lens wear during the study period

General:

1. Resting heart rate (HR) outside the normal range (60 - 100 beats per minute)

2. Hypertension diastolic blood pressure (BP) > 105 mm Hg

3. Use of monoamine oxidase inhibitors (MAOIs; eg, isocarboxazid, phenelzine, tranylcypromine) within 14 days prior to Visit 1 or during the study

4. Use of beta blockers (eg, propranolol, metoprolol, labetalol) within 14 days prior to Visit 1 or during the study

5. 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

6. A history of myocardial infarction, angina, arrhythmia, or irregular pulse

7. Advanced arteriosclerotic disease

8. History of thyroid disease

9. Insulin-dependent diabetes or diabetes requiring oral hypoglycemic drugs; diet-controlled diabetes is allowed

10. Pregnancy or lactation

11. Diagnosed benign prostatic hypertrophy requiring medicinal therapy.

12. History of contact or systemic allergic reaction to oxymetazoline or other sympathomimetic drugs (eg, phenylephrine, pseudoephedrine, ephedrine, phenylpropanolamine, fepradinol, or methoxamine)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Morrow	Georgia	United States	30260

Sponsors and Collaborators

• RVL Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Chuck Slonim, MD, Oculos Clinical Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: RVL Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01848041
• Other Study ID Numbers: RVL-1201-001
• First Posted: May 7, 2013
• Last Update Posted: Nov 26, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by RVL Pharmaceuticals, Inc.: Blepharoptosis; Ptosis
• Additional relevant MeSH terms: Blepharoptosis; Phenylephrine; Oxymetazoline; Pharmaceutical Solutions; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	RVL-1201 QD	RVL-1201 BID	RVL-1201 Vehicle (Placebo) BID
Arm/Group 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: RVL-1201 0.1% Ophthalmic Solution	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: RVL-1201 0.1% Ophthalmic Solution	RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose RVL-1201 Vehicle Placebo: RVL-1201 Vehicle Placebo
Period Title: Overall Study
STARTED	15	16	15
COMPLETED	15	16	15
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	RVL-1201 QD	RVL-1201 BID	RVL-1201 Vehicle (Placebo) BID	Total
Arm/Group 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: RVL-1201 0.1% Ophthalmic Solution	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: RVL-1201 0.1% Ophthalmic Solution	RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose RVL-1201 Vehicle Placebo: RVL-1201 Vehicle Placebo	Total of all reporting groups
Overall Participants	15	16	15	46
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 53.3%	13 81.3%	10 66.7%	31 67.4%
>=65 years	7 46.7%	3 18.8%	5 33.3%	15 32.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.3 (10.33)	58.7 (10.47)	58.3 (11.23)	60.4 (10.80)
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	63	60	60	61.5
Sex: Female, Male (Count of Participants)
Female	13 86.7%	10 62.5%	11 73.3%	34 73.9%
Male	2 13.3%	6 37.5%	4 26.7%	12 26.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 73.3%	9 56.3%	9 60%	29 63%
Not Hispanic or Latino	4 26.7%	7 43.8%	6 40%	17 37%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 6.3%	1 6.7%	2 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 6.3%	2 13.3%	3 6.5%
White	15 100%	14 87.5%	12 80%	41 89.1%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	15 100%	16 100%	15 100%	46 100%
Iris Color OD/OS (Count of Participants)
Blue	4 26.7%	4 25%	1 6.7%	9 19.6%
Brown	10 66.7%	11 68.8%	13 86.7%	34 73.9%
Green	0 0%	1 6.3%	1 6.7%	2 4.3%
Hazel	1 6.7%	0 0%	0 0%	1 2.2%
Grey	0 0%	0 0%	0 0%	0 0%
Other	0 0%	0 0%	0 0%	0 0%
Blue	4 26.7%	4 25%	1 6.7%	9 19.6%
Brown	10 66.7%	11 68.8%	13 86.7%	34 73.9%
Green	0 0%	1 6.3%	1 6.7%	2 4.3%
Hazel	1 6.7%	0 0%	0 0%	1 2.2%
Grey	0 0%	0 0%	0 0%	0 0%
Other	0 0%	0 0%	0 0%	0 0%
Lens Status OD/OS (Count of Participants)
Phakic, a person with an intact natural lens	9 60%	11 68.8%	11 73.3%	31 67.4%
Aphakic, a person with a natural lens was extracted and no intraocular lens was implanted.	0 0%	0 0%	0 0%	0 0%
Pseudophakic, a person who has had a lens extracted and an intraocular lens placed	6 40%	5 31.3%	4 26.7%	15 32.6%
Phakic, a person with an intact natural lens	9 60%	12 75%	11 73.3%	32 69.6%
Aphakic, a person with a natural lens was extracted and no intraocular lens was implanted.	0 0%	0 0%	0 0%	0 0%
Pseudophakic, a person who has had a lens extracted and an intraocular lens placed	6 40%	4 25%	4 26.7%	14 30.4%

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	RVL-1201 Once Daily	RVL-1201 Twice Daily	RVL-1201 Vehicle (Placebo)
Arm/Group 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: RVL-1201 0.1% Ophthalmic Solution	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: RVL-1201 0.1% Ophthalmic Solution	RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose RVL-1201 Vehicle Placebo: RVL-1201 Vehicle Placebo
Measure Participants	15	16	15
Base Line (Day 0, Hour 0)	9.8 (5.07)	12.1 (4.64)	11.1 (4.74)
Visit 4 (Day 13, Hour 2)	16.1 (5.35)	15.7 (4.63)	15.7 (5.64)
Visit 4 (Day 13, Hour 6)	15.9 (5.29)	17.0 (4.51)	17.1 (5.02)

2. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	RVL-1201 Once Daily	RVL-1201 Twice Daily	RVL-1201 Vehicle (Placebo)
Arm/Group 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: RVL-1201 0.1% Ophthalmic Solution	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: RVL-1201 0.1% Ophthalmic Solution	RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose RVL-1201 Vehicle Placebo: RVL-1201 Vehicle Placebo
Measure Participants	15	16	15
Baseline (Day 0, Hour 0)	1.6 (0.77)	1.6 (0.84)	1.6 (0.63)
Visit 4 (Day 13, Hour 2)	2.4 (0.99)	2.3 (1.19)	2.0 (0.95)
Visit 4 (Day 13, Hour 6)	2.4 (1.00)	2.5 (1.13)	2.2 (1.07)

3. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	RVL-1201 Once Daily	RVL-1201 Twice Daily	RVL-1201 Vehicle (Placebo)
Arm/Group 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: RVL-1201 0.1% Ophthalmic Solution	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: RVL-1201 0.1% Ophthalmic Solution	RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose RVL-1201 Vehicle Placebo: RVL-1201 Vehicle Placebo
Measure Participants	15	16	15
Baseline (Day 0, Hour 0)	6.2 (1.16)	6.5 (1.10)	6.5 (1.55)
Visit 4 (Day 13, Hour 2)	6.9 (1.35)	7.1 (1.72)	6.6 (1.67)
Visit 4 (Day 13, Hour 6)	7.0 (1.51)	7.5 (1.45)	6.8 (1.35)

4. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	RVL-1201 Once Daily	RVL-1201 Twice Daily	RVL-1201 Vehicle (Placebo)
Arm/Group 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: RVL-1201 0.1% Ophthalmic Solution	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: RVL-1201 0.1% Ophthalmic Solution	RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose RVL-1201 Vehicle Placebo: RVL-1201 Vehicle Placebo
Measure Participants	15	16	15
Baseline (Day 0, Hour 0)	33.1 (4.05)	34.7 (6.14)	33.3 (5.81)
Visit 4 (Day 13, Hour 2)	34.7 (4.45)	35.8 (4.28)	35.3 (4.79)
Visit 4 (Day 13, Hour 6)	35.5 (3.81)	36.8 (3.29)	35.1 (4.18)

5. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	RVL-1201 QD	RVL-1201 BID	RVL-1201 Vehicle (Placebo) BID
Arm/Group 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: RVL-1201 0.1% Ophthalmic Solution	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: RVL-1201 0.1% Ophthalmic Solution	RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose RVL-1201 Vehicle Placebo: RVL-1201 Vehicle Placebo
Measure Participants	15	16	15
Baseline (Day 0, Hour 0)	0.071 (0.0859)	0.086 (0.0988)	0.081 (0.0770)
Visit 4 (Day 13, Hour 2)	0.055 (0.0739)	0.024 (0.1043)	0.059 (0.1190)
Visit 4 (Day 13, Hour 6)	0.026 (0.0891)	0.023 (0.0949)	0.053 (0.1018)

Adverse Events

Time Frame	14 Days
Adverse Event Reporting Description	AEs were those with onset after randomization or if occurring prior to randomization, that worsened after randomization.
Arm/Group Title	RVL-1201 QD		RVL-1201 BID		RVL-1201 Vehicle (Placebo) BID
Arm/Group 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: RVL-1201 0.1% Ophthalmic Solution		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: RVL-1201 0.1% Ophthalmic Solution		RVL 1201 ophthalmic solution vehicle (placebo) dosed one full drop per eye BID; approximately 8 hours between the morning dose and the afternoon dose RVL-1201 Vehicle Placebo: RVL-1201 Vehicle Placebo
All Cause Mortality
	RVL-1201 QD		RVL-1201 BID		RVL-1201 Vehicle (Placebo) BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/16 (0%)		0/15 (0%)
Serious Adverse Events
	RVL-1201 QD		RVL-1201 BID		RVL-1201 Vehicle (Placebo) BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/16 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	RVL-1201 QD		RVL-1201 BID		RVL-1201 Vehicle (Placebo) BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)		5/16 (31.3%)		1/15 (6.7%)
Eye disorders
Punctate keratitis	1/15 (6.7%)	2	0/16 (0%)	0	0/15 (0%)	0
Ocular Discomfort	0/15 (0%)	0	1/16 (6.3%)	2	0/15 (0%)	0
General disorders
Instillation Site Dryness	1/15 (6.7%)	2	0/16 (0%)	0	0/15 (0%)	0
Instillation Site Foreign Body Sensation	1/15 (6.7%)	2	2/16 (12.5%)	4	0/15 (0%)	0
Instillation Site Pruritus	1/15 (6.7%)	4	1/16 (6.3%)	2	0/15 (0%)	0
Instillation Site Pain	0/15 (0%)	0	2/16 (12.5%)	3	0/15 (0%)	0
Infections and infestations
Upper respiratory tract infection	0/15 (0%)	0	0/16 (0%)	0	1/15 (6.7%)	1
Nervous system disorders
Headache	1/15 (6.7%)	1	0/16 (0%)	0	0/15 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.