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Study of Safety and Efficacy of RVL-1201 in the Treatment of Blepharoptosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03565887
Recruitment Status : Completed
First Posted : June 21, 2018
Results First Posted : September 16, 2020
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
RVL Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Blepharoptosis
Interventions Drug: RVL-1201
Other: Vehicle ophthalmic solution
Enrollment 164
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.
Pre-assignment Details  
Arm/Group Title RVL-1201 Ophthalmic Solution 0.1% Vehicle Ophthalmic Solution
Hide Arm/Group Description RVL-1201 (oxymetazoline hydrochloride) ophthalmic solution 0.1% One drop each eye once-daily in the morning Vehicle placebo ophthalmic Solution One drop each eye once-daily in the morning
Period Title: Overall Study
Started 109 55
Completed 108 53
Not Completed 1 2
Reason Not Completed
Adverse Event             1             0
Withdrawal by Subject             0             2
Arm/Group Title RVL-1201 Ophthalmic Solution 0.1% Vehicle Ophthalmic Solution Total
Hide Arm/Group Description RVL-1201 (oxymetazoline hydrochloride) ophthalmic solution 0.1% One drop each eye QD in the morning Vehicle placebo ophthalmic Solution One drop each eye QD in the morning Total of all reporting groups
Overall Number of Baseline Participants 109 55 164
Hide Baseline Analysis Population Description
Intent to Treat (ITT) Population
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 55 participants 164 participants
<=18 years
0
   0.0%
1
   1.8%
1
   0.6%
Between 18 and 65 years
46
  42.2%
22
  40.0%
68
  41.5%
>=65 years
63
  57.8%
32
  58.2%
95
  57.9%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 109 participants 55 participants 164 participants
63.6  (14.31) 63.3  (16.51) 63.5  (15.03)
Age, Customized  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 109 participants 55 participants 164 participants
67.0
(20 to 92)
67.0
(14 to 85)
67.0
(14 to 92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 55 participants 164 participants
Female
77
  70.6%
39
  70.9%
116
  70.7%
Male
32
  29.4%
16
  29.1%
48
  29.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 55 participants 164 participants
Hispanic or Latino
13
  11.9%
6
  10.9%
19
  11.6%
Not Hispanic or Latino
96
  88.1%
49
  89.1%
145
  88.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 55 participants 164 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
4
   3.7%
2
   3.6%
6
   3.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   5.5%
3
   5.5%
9
   5.5%
White
99
  90.8%
50
  90.9%
149
  90.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 109 participants 55 participants 164 participants
109 55 164
Iris Color OD (right eye)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 55 participants 164 participants
OD-Blue
40
  36.7%
18
  32.7%
58
  35.4%
OD-Brown
46
  42.2%
18
  32.7%
64
  39.0%
OD-Green
7
   6.4%
3
   5.5%
10
   6.1%
OD-Hazel
15
  13.8%
15
  27.3%
30
  18.3%
OD-Grey
1
   0.9%
1
   1.8%
2
   1.2%
Iris Color OS (left eye)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 55 participants 164 participants
OS-Blue
40
  36.7%
18
  32.7%
58
  35.4%
OS-Brown
47
  43.1%
18
  32.7%
65
  39.6%
OS-Green
6
   5.5%
3
   5.5%
9
   5.5%
OS-Hazel
15
  13.8%
15
  27.3%
30
  18.3%
OS-Grey
1
   0.9%
1
   1.8%
2
   1.2%
1.Primary Outcome
Title Mean Change in Number of Points Seen on the Leicester Peripheral Field Test (LPFT) in RVL-1201 Group vs. Vehicle Group
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title RVL-1201 Ophthalmic Solution 0.1% Vehicle Ophthalmic Solution
Hide Arm/Group Description:
RVL-1201 (oxymetazoline hydrochloride) ophthalmic solution 0.1% One drop each eye QD in the morning
Vehicle placebo ophthalmic Solution One drop each eye QD in the morning
Overall Number of Participants Analyzed 109 55
Mean (Standard Deviation)
Unit of Measure: Points seen
Mean change from baseline LPFT-Day 1 Hour 6 6.3  (6.72) 2.1  (4.28)
Mean change from baseline LPFT-Day 14 Hour 2 7.7  (6.41) 2.4  (5.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RVL-1201 Ophthalmic Solution 0.1%, Vehicle Ophthalmic Solution
Comments 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).
Type of Statistical Test Superiority
Comments The primary efficacy endpoints were tested sequentially. The Day 1 Hour 6 time point was tested first and if P<0.05, the Day 14 Hour 2 time point was tested at a significance level of 0.05. If the Day 1 Hour 6 endpoint is statistically significant (at the 0.05 level) but Day 14 Hour 2 was not statistically significant (at the 0.05 level), the study will still be considered positive.
Statistical Test of Hypothesis P-Value <0.0001
Comments If both primary endpoints (LPFT) are significant at 0.05 significance level, then the secondary efficacy endpoints (MRD) were also tested sequentially. Testing stopped if a P≥ 0.05 for a comparison.
Method ANCOVA
Comments 2 sided t-test with treatment as fixed factor and baseline as covariate.
2.Secondary Outcome
Title Mean Change From Baseline in Marginal Reflex Distance (MRD) in the Study Eye
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title RVL-1201 Ophthalmic Solution 0.1% Vehicle Ophthalmic Solution
Hide Arm/Group Description:
RVL-1201 (oxymetazoline hydrochloride) ophthalmic solution 0.1% One drop each eye QD in the morning
Vehicle placebo ophthalmic Solution One drop each eye QD in the morning
Overall Number of Participants Analyzed 109 55
Mean (Standard Deviation)
Unit of Measure: Millimeters (mm)
Day 1, Minute 5 0.59  (0.721) 0.20  (0.571)
Day 1, Minute 15 0.93  (0.811) 0.32  (0.641)
Day 1, Hour 2 1.05  (0.903) 0.33  (0.555)
Day 1, Hour 6 0.98  (0.867) 0.35  (0.567)
Day 14, Minute 5 0.77  (0.853) 0.42  (0.775)
Day 14, Minute 15 1.11  (0.922) 0.41  (0.833)
Day 14, Hour 2 1.22  (0.926) 0.43  (0.734)
Day 14, Hour 6 1.06  (0.902) 0.47  (0.737)
Day 42, Minute 5 0.86  (0.849) 0.42  (0.799)
Day 42, Minute 15 1.04  (0.912) 0.47  (0.926)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RVL-1201 Ophthalmic Solution 0.1%, Vehicle Ophthalmic Solution
Comments 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).
Type of Statistical Test Superiority
Comments If both primary endpoints (LPFT) are significant at 0.05 significance level, then the secondary efficacy endpoints (MRD) were also tested sequentially. Testing stopped if a P≥ 0.05 for a comparison.
Statistical Test of Hypothesis P-Value <0.0151
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Time Frame Treatment-emergent adverse events (AEs) were assessed at Baseline through Day 42 (end of study).
Adverse Event Reporting Description AEs spontaneously reported by the subject and/or in response to an open questions from the study personnel or revealed by observation were recorded in the eCRF.
 
Arm/Group Title RVL-1201 Ophthalmic Solution, 0.1% Vehicle Ophthalmic Solution
Hide Arm/Group Description One drop each eye QD in the morning (n=109) One drop each eye QD in the morning (n=55)
All-Cause Mortality
RVL-1201 Ophthalmic Solution, 0.1% Vehicle Ophthalmic Solution
Affected / at Risk (%) Affected / at Risk (%)
Total   0/109 (0.00%)      0/55 (0.00%)    
Hide Serious Adverse Events
RVL-1201 Ophthalmic Solution, 0.1% Vehicle Ophthalmic Solution
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/109 (0.92%)      1/55 (1.82%)    
Gastrointestinal disorders     
Lower gastrointestinal haemorrhage * 1  0/109 (0.00%)  0 1/55 (1.82%)  1
Nervous system disorders     
Cerebrovascular accident * 1  1/109 (0.92%)  1 0/55 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
RVL-1201 Ophthalmic Solution, 0.1% Vehicle Ophthalmic Solution
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/109 (11.93%)      8/55 (14.55%)    
Eye disorders     
Conjunctival hyperaemia * 1  6/109 (5.50%)  10 1/55 (1.82%)  2
Punctate keratitis * 1  4/109 (3.67%)  8 1/55 (1.82%)  1
Eye pain * 1  3/109 (2.75%)  4 0/55 (0.00%)  0
Eye pruritus * 1  0/109 (0.00%)  0 2/55 (3.64%)  4
General disorders     
Instillation site complication * 1 [1]  0/109 (0.00%)  0 2/55 (3.64%)  4
Investigations     
Vital dye straining cornea present * 1  1/109 (0.92%)  2 3/55 (5.45%)  4
1
Term from vocabulary, MedDRA 21.0
*
Indicates events were collected by non-systematic assessment
[1]
Administration site conditions
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Director of Clinical Operations
Organization: RVL Pharmaceuticals, Inc.
Phone: 908-809-1423
EMail: mvelasco@osmotica.com
Layout table for additonal information
Responsible Party: RVL Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03565887    
Other Study ID Numbers: RVL-1201-202
First Submitted: April 11, 2018
First Posted: June 21, 2018
Results First Submitted: August 4, 2020
Results First Posted: September 16, 2020
Last Update Posted: September 16, 2020