7. Project Summary/Abstract
The project is a Phase II clinical study of Civamide Nasal Spray for the treatment of Dry Eye Disease, an
irritating and potentially severely disabling ocular disease. If this study is successful in the treatment of Dry Eye
Disease, further clinical development will proceed, i.e., Phase 3 studies to support the filing of a New Drug
Application. Currently, all approved medications for treating Dry Eye Disease are directly instilled into the eye
with the possibility of ocular side effects. Civamide Nasal Spray is unique in that it exerts its therapeutic effect
locally in the nasal mucosa without systemic absorption being detected, as shown in a pharmacokinetic study.1
The availability of a safe and effective medication for Dry Eye Disease for these patients, i.e., Civamide Nasal
Spray, will thus fill an unmet medical need.
Civamide, a TRPV-1 receptor modulator,2,3 is a medication with a mechanism of action that affects nerves by
modulating the synthesis, release, and transport of neurotransmitters. Dry Eye Disease is a disease of the
surface of the eye, tear film, and related ocular tissues, including mucosal glands, which in part, are innervated
by the trigeminal nerve.4,5,6 The trigeminal nerve also has superficial nerve endings in the nasal mucosa, which
are the targets of Civamide Nasal Spray. By affecting these nerve endings, neurotransmitter physiology is
affected throughout the entire nerve. Increased lacrimation as a result of this novel mechanism of action has
been observed when Civamide Nasal Spray is applied to the nasal mucosa in both normal subjects and
subjects with headache disorders mediated by the trigeminal nerve, e.g., migraine headache7 and cluster
headache8.
This proposed study is a 12 week, double-blind, vehicle-controlled study of adult subjects that have moderate
to severe Dry Eye Disease for at least 6 months, and a Schirmer’s Test of = 8 per 5 minutes in at least one eye
at screening and baseline. The study is composed of a non-treatment Screening Period during which subjects
will be required to meet study inclusion criteria, followed by a 12-week Double-Blind Treatment Period.
Subjects will be randomized 1:1, approximately 20 subjects per group. The primary outcome variable will be
the change in the Schirmer’s Test from Baseline to Day 84 of the Treatment Period. Adverse events will be
recorded during the study.