- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01848041
Safety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis
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 Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Georgia
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Morrow, Georgia, United States, 30260
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / 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
|
RVL-1201 0.1% Ophthalmic Solution
Other Names:
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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
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RVL-1201 0.1% Ophthalmic Solution
Other Names:
|
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
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RVL-1201 Vehicle Placebo
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Humphrey Visual Field
Time Frame: 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:
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. |
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Marginal Reflex Distance
Time Frame: 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. |
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
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Palpebral Fissure Distance Measurement
Time Frame: Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
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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. |
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
|
Contrast Sensitivity
Time Frame: Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
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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). |
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
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Corrected Snellen Visual Acuity
Time Frame: Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
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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). |
Baseline (Day 0, Hour 0), Visit 4 (Day 13, Hour 2) and Visit 4 (Day 13, Hour 6)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Chuck Slonim, MD, Oculos Clinical Research
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Eye Diseases
- Eyelid Diseases
- Blepharoptosis
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Protective Agents
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Cardiotonic Agents
- Respiratory System Agents
- Sympathomimetics
- Vasoconstrictor Agents
- Mydriatics
- Nasal Decongestants
- Adrenergic alpha-1 Receptor Agonists
- Ophthalmic Solutions
- Pharmaceutical Solutions
- Phenylephrine
- Oxymetazoline
Other Study ID Numbers
- RVL-1201-001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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