A Double-Blind Study Evaluating the Safety and Efficacy of Cyclosporine Ophthalmic Emulsion 0.05% [Restasis] in Subjects With Epiphora Secondary to Docetaxel [Taxotere] Treatment for Various Cancers
The Study Drugs:
Restasis® is also known as cyclosporine ophthalmic emulsion 0.05% (cyclosporine eye drops).
It is designed to decrease eye inflammation.
FML Forte® is also known as fluorometholone 0.25% ophthalmic suspension (fluorometholone eye
drops). It is designed to decrease eye inflammation. Fluorometholone eye drops are
commonly used to help to control epiphora.
In this study, an additional type of eye drops will be used for comparison with cyclosporine
eye drops. This second type of eye drops is called Refresh Endura™ (lubricant eye drops),
which is designed to relieve dry eyes. Unlike cyclosporine and fluorometholone, it does not
have active ingredients designed to treat epiphora.
If you are found to be eligible to take part in this study, you will be assigned to 1 of 2
groups. The way of assigning participants to groups is mostly random, as in the flip of a
coin. However, your epiphora score (how often you dabbed your tears, as recorded in a
diary) will also affect what group you are assigned to.
Group 1 will receive cyclosporine eye drops and fluorometholone eye drops. Group 2 will
receive lubricant eye drops and fluorometholone eye drops.
Neither you nor the study staff will know whether you are receiving cyclosporine eye drops
or lubricant eye drops. However, if needed for your safety, the study staff will be able to
find out which one you are receiving.
Study Drug Administration Your first dose of the study drugs will be given in the clinic on
Day 1. After that, you will give yourself the rest of the doses at home. The study staff
will teach you how to use the eye drops, and you will be given written instructions. Study
data will be collected on both eyes, and you will apply the drops to both eyes.
If you wear contact lenses, be sure to take your contact lenses out before using the eye
drops. Fifteen (15) minutes after your dose of the eye drops, you may put your contact
lenses back in.
If you are in Group 1, you will apply 1 drop of cyclosporine eye drops to each eye, 2 times
a day, for 84 days (12 weeks) in a row. You should wait about 12 hours between doses.
If you are in Group 2, you will apply 1 drop of lubricant eye drops to each eye, 2 times a
day, for 84 days in a row. You should wait about 12 hours between doses.
All study participants must wait at least 10 minutes after you have applied your other eye
drops (cyclosporine or the lubricant) before you can apply the fluorometholone eye drops.
All study participants will receive fluorometholone eye drops. During Week 1, you will
apply 1 drop to each eye, 4 times a day. During Week 2, you will apply 1 drop to each eye,
3 times a day. During Week 3, you will apply 1 drop to each eye, 2 times a day. During
Week 4, you will apply 1 drop to each eye, once a day.
On Visit 1 (Day -1 or -2), your eye doctor and/or study staff will ask you to sign the
written informed consent. Screening tests will be done, which include urine pregnancy test
for all women who are able to become pregnant, and other eye exams, such as Best Corrected
Visual Acuity, Biomicroscopy, Intraocular Pressure (IOP), Epiphora Assessments, Schirmer's
Test, and Probing and Irrigation Test. Your eye doctor and/or assistant will explain these
different eye exams, or any questions you may have, at the day of your visit. You will also
be asked about the different medications that you are currently taking. You will be given
participant diaries for you to record or keep track of your medication use and how many
times you dab your tears. You will then be given the schedule of your next visit.
On Visit 2 (Day 0 or baseline), the study staff will record how well you tolerate the study
drugs and any side effects that may occur after the doses. You will also complete 2
questionnaires. The first questionnaire asks about the quality of your life and the second
questionnaire asks about any problems with your vision that you may be experiencing. In
total, they should take about 10-15 minutes to complete.
You will be given additional patient diaries. In the first diary, you will record any
missed doses of the study drugs. In the second diary, you will record how many times you
dab tears from your eyes and/or face, starting 24 hours before each clinic visit.
You should bring the completed patient diaries and the used containers of the study drugs
with you to every study visit.
At Weeks 2, 4, and 8, the following procedures will be performed:
- You will have a routine eye exam to check the status of the epiphora. The same eye
tests will be performed as at screening. However, the routine procedure called
"probing and irrigation" (a test of the tear ducts, involving water) may not need to be
repeated. The probing and irrigation procedure will only be performed if the epiphora
seems to have gotten worse. In that case, the probing and irrigation procedure will
help the doctor decide whether to recommend that you consider additional treatments.
- You will be asked about any side effects you may have experienced, any other drugs or
treatments you may be receiving, and any other changes to your current drugs or
- You will repeat the quality-of-life questionnaire. You will also complete a second
questionnaire about your overall eye comfort and a third questionnaire about the eye
tearing symptoms. In total, these questionnaires should take about 20 minutes to
Length of Study Participation:
You may stay on study treatment for up to 12 weeks. If intolerable side effects occur, or
the epiphora gets worse and the study doctor thinks you should consider surgery to treat it,
you will be taken off study treatment early.
After your last dose of the study drugs (at Week 12, or earlier if you go off study
treatment early), you will return for an end-of-study visit. At this visit, the following
procedures will be performed:
- You will have the same procedures performed as at Weeks 2, 4, and 8.
- You will complete the quality-of-life questionnaire, the questionnaire that asks about
any problems with your vision, and the questionnaire that asks if your eye tearing
symptoms have improved or gotten worse compared to the days before you started the
study. In total, these questionnaires should take about 20 minutes to complete.
- Women who are able to have children will have a urine pregnancy test.
THIS IS AN INVESTIGATIONAL STUDY. Cyclosporine eye drops, fluorometholone eye drops, and
Refresh Endura™ lubricant eye drops are commercially available for other eye conditions.
They are not FDA approved for use in treating epiphora. At this time and for this purpose,
they are considered experimental. This includes fluorometholone eye drops, which are
commonly used to treat epiphora but are not FDA approved for this use.
Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Patient Epiphora Grade Scores
Epiphora score (how often dabbed tears, as recorded in a diary) assessed on a five-point scale to grade epiphora: 0: None; 1: Trace; 2: Mild; 3: Moderate; 4: Severe. It is evaluated at Day 0, Weeks 2, 4, 8 and 12. The within-arm comparison made between baseline (Day 0) and Week 4.
Evaluated at Day 0 (Baseline) through Week 12
Bita Esmaeli, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration