Study of the Safety and Efficacy of RVL-1201 in the Treatment of Acquired Blepharoptosis
Condition: Acquired Blepharoptosis
MeSH terms: Blepharoptosis
Intervention: RVL-1201; RVL-1201 Vehicle Placebo
Intervention description: RVL-1201 Ophthalmic Solution 0.1%; RVL-1201 Vehicle Placebo
Intervention MeSH terms: Phenylephrine; Oxymetazoline; Pharmaceutical Solutions; Ophthalmic Solutions
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 140.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase 3 study is to evaluate the safety and efficacy of RVL-1201 Ophthalmic
      Solution in the treatment of acquired blepharoptosis (ptosis) and to assess the safety and
      comfort of RVL-1201 Ophthalmic Solution for an extended dosing period of 6 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subjects 18 years of age and older.

          2. Presence of all of the following at Screening :

             a. Loss on a reliable LPFT of ≥ 8 points in the top 2 rows (LPFT Eligibility Score);
             subjects must see at least 9 total points in the top 4 rows (LPFT Total Score).

             i. This criteria must be met at both the Visit 1 Hour 0 (V1H0) and Visit 1 Hour 6
             (V1H6) LPFT assessments

             ii. There must be ≤ 4 points of variance between the V1H0 and the V1H6 LPFT
             Eligibility Score;; AND

             b. The MRD, the distance from the central pupillary light reflex to the central margin
             of the upper lid, must be ≤ 2 mm (no visible central pupillary light reflex defaults
             to 0) in the same eye as Inclusion Criterion #2a

             AND

             c. Snellen visual acuity (VA) of 20/80 or better in the same eye as Inclusion Criteria
             #2a and #2b.

          3. Presence of all of the following at Baseline:

             a. Loss on a reliable LPFT of ≥ 8 points in the top 2 rows (LPFT Eligibility Score) in
             the same eye as Inclusion Criterion #2a; subjects must see at least 9 total points in
             the top 4 rows (LPFT Total Score).

             i. This criteria must be met at the Visit 2 Hour 0 (V2H0) LPFT assessment. ii. There
             must be ≤ 4 points of variance between the V1H6 and the V2H0 LPFT Eligibility Score;

             AND

             b. Marginal Reflex Distance (MRD), the distance from the central pupillary light
             reflex to the central margin of the upper lid, must be ≤ 2 mm (no visible central
             pupillary light reflex defaults to 0) in the same eye as Inclusion Criterion #2a;

             AND

             c. Snellen VA of 20/80 or better in the same eye as Inclusion Criteria #2a and #2b.

          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. Acceptable methods include the use of at least one of the following:
             intrauterine (intrauterine device), hormonal (oral, injection, patch, implant, ring),
             barrier with spermicide (condom, diaphragm), or abstinence.

          5. Able to self-administer study medication or to have the study medication administered
             by a caregiver throughout the study period.

          6. Subjects must be able to understand and sign an IRB approved informed consent form
             prior to participation in any study-related procedures.

        Exclusion Criteria:

        In either eye

          1. Congenital ptosis.

          2. Presence of either of the following:

               1. Pseudoptosis (upper eyelid dermatochalasis that overhangs the upper eyelid
                  margin) or

               2. Dermatochalasis that extends less than 3 mm above the upper eyelid margin.

          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. Previous ptosis surgery (previous blepharoplasty [only] is allowed provided the
             surgery took place > 3 months prior to Visit 1).

          8. Lid position affected by lid or conjunctival scarring.

          9. Visual field loss from any cause other than ptosis.

         10. History of herpes keratitis.

         11. History of closed/narrow angle glaucoma (unless patent peripheral iridotomy has been
             performed > 3 months prior to Visit 1).

         12. Periocular neurotoxin (eg, Botox, Xeomin, Dysport, Myobloc) injections within 3 months
             prior to Visit 1 and during the study.

         13. Topical application of bimatoprost (ie, Latisse®) to the eyelashes within 7 days prior
             to Visit 1 and during the study.

         14. Use of topical ophthalmic medications (including anti-allergy [eg, antihistamines],
             dry eye [ie, Restasis®] and anti-inflammatory drugs [including nonsteroidal
             anti-inflammatory drugs (NSAIDs) and steroids] other than the assigned study
             medication within 7 days prior to Visit 1 and during the study. Topical ophthalmic
             prostaglandin analogues for the treatment of elevated intraocular pressure are
             permitted if dosed in the evening in accordance with the approved prescribing
             information. All other topical antiglaucoma medications are prohibited

         15. Intravitreal injections (eg, Lucentis®, Eylea®, Avastin®, Triesence®) within 7 days
             prior to Visit 1 and during the study.

         16. Current punctal plugs or placement of punctal plugs during the study.

         17. Use of over the counter (OTC) vasoconstrictor/decongestant eye medication (eg, Visine®
             L.R.®) or any ophthalmic or non-ophthalmic α adrenergic agonist including OTC products
             (eg, Afrin®) at any time during the study; nonpreserved artificial tears are allowed.

             General

         18. Resting heart rate (HR) outside the normal range (60-100 beats per minute).

         19. Hypertension with resting diastolic blood pressure (BP) > 105 mm Hg.

         20. Use of monoamine oxidase inhibitors (MAOIs; eg, isocarboxazid, phenelzine,
             tranylcypromine) within 14 days prior to Visit 1 and during the study.

         21. Advanced arteriosclerotic disease or history of cerebrovascular accident (CVA).

         22. History of hyperthyroidism or thyroid eye disease (ie, exophthalmos, upper eyelid
             retraction, diplopia secondary to extraocular muscle involvement). Hypothyroidism that
             is controlled on medication is allowed.

         23. Patients with diabetic retinopathy may not be enrolled. However, patients with insulin
             dependent diabetes, diabetes requiring oral hypoglycemic drugs, or diet controlled
             diabetes are allowed.

         24. Pregnancy or lactation.

         25. Diagnosed benign prostatic hypertrophy requiring medicinal therapy; previous
             prostatectomy is allowed.

         26. History of contact or systemic allergic reaction to oxymetazoline or other
             sympathomimetic drugs (eg, phenylephrine, pseudoephedrine, ephedrine,
             phenylpropanolamine, fepradinol, or methoxamine).