Safety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
RevitaLid Inc.
ClinicalTrials.gov Identifier:
NCT01848041
First received: May 3, 2013
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Blepharoptosis
Drug: RVL-1201
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Further study details as provided by RevitaLid Inc.:

Primary Outcome Measures:
  • Humphrey Visual Field [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    The mean increase from baseline (Day 0, Hour 0) in number of points seen on the HVF 36-point ptosis protocol test at various times on Day 0 and Day 13 according to a pre-planned hierarchical analysis


Secondary Outcome Measures:
  • Marginal Reflex Distance [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    The Pelli-Robson contrast sensitivity chart will be used at a distance of 1 meter.

  • Safety [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Assessment of the safety and tolerability of RVL-1201 compared to vehicle will include bilateral ophthalmic examinations (corrected Snellen VA, pupil diameter measurement, slit lamp examination (SLE)/corneal fluorescein (CF) staining, IOP tonometry, ophthalmoscopy/fundus exam), measurement of vital signs, and recording of adverse events.


Enrollment: 46
Study Start Date: May 2013
Study Completion Date: February 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult male or female subjects 18 years of age and older.
  2. Presence of all of the following at Screening:

    1. 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
    2. 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
    3. 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.
  3. No contraindications for treatment of both eyes as specified in Exclusion Criteria #1-14.
  4. 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.
  5. 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:

  17. Resting heart rate (HR) outside the normal range (60 - 100 beats per minute)
  18. Hypertension diastolic blood pressure (BP) > 105 mm Hg
  19. Use of monoamine oxidase inhibitors (MAOIs; eg, isocarboxazid, phenelzine, tranylcypromine) within 14 days prior to Visit 1 or during the study
  20. Use of beta blockers (eg, propranolol, metoprolol, labetalol) within 14 days prior to Visit 1 or during the study
  21. 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
  22. A history of myocardial infarction, angina, arrhythmia, or irregular pulse
  23. Advanced arteriosclerotic disease
  24. History of thyroid disease
  25. Insulin-dependent diabetes or diabetes requiring oral hypoglycemic drugs; diet-controlled diabetes is allowed
  26. Pregnancy or lactation
  27. Diagnosed benign prostatic hypertrophy requiring medicinal therapy.
  28. History of contact or systemic allergic reaction to oxymetazoline or other sympathomimetic drugs (eg, phenylephrine, pseudoephedrine, ephedrine, phenylpropanolamine, fepradinol, or methoxamine)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01848041

Locations
United States, California
Sall Research Medical Center
Artesia, California, United States, 90701
United States, Georgia
Clayton Eye Center
Morrow, Georgia, United States, 30260
United States, Texas
Texan Eye/Keystone Research
Austin, Texas, United States, 78731
The Cataract and Glaucoma Center
El Paso, Texas, United States, 79902
Medical Center Ophthalmology Associates
San Antonio, Texas, United States, 78240
Sponsors and Collaborators
RevitaLid Inc.
  More Information

No publications provided

Responsible Party: RevitaLid Inc.
ClinicalTrials.gov Identifier: NCT01848041     History of Changes
Other Study ID Numbers: RVL-1201-001
Study First Received: May 3, 2013
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by RevitaLid Inc.:
Blepharoptosis
Ptosis

Additional relevant MeSH terms:
Blepharoptosis
Eyelid Diseases
Eye Diseases
Ophthalmic Solutions
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014