The project is the initial proof of concept clinical study of Civamide Nasal Spray for the treatment of postherpetic neuralgia (PHN) of the trigeminal nerve [(TN), a severely disabling facial pain syndrome]. Civamide Nasal Spray as a treatment for PHN of the [TN] has previously been granted orphan drug designation. If this study is successful in the treatment of PHN of the [TN], further clinical development will proceed, i.e., Phase 2 and Phase 3 studies to support the filing of a New Drug Application. Currently, all approved medications for treating PHN of the [TN] are systemically acting drugs. Civamide Nasal Spray is unique in that it exerts its therapeutic effect locally without systemic absorption [being detected in a pharmacokinetic study.8] The availability of a safe and effective medication for PHN of the [TN] for these patients, i.e., Civamide Nasal Spray, will thus fill an unmet medical need. Civamide, a TRPV-1 receptor modulator,1,2 is a medication [with a mechanism of action] that affects nerves by causing a depletion of neurotransmitters, thus making the nerve less able to transmit pain.25,26 PHN of the [TN] is a chronic condition characterized by extreme pain following herpes zoster infection, (commonly called shingles,) in the areas of the face and scalp which are innervated by the [TN].3,4,5 The [TN] also has superficial nerve endings in the nasal mucosa, which are the targets of Civamide Nasal Spray. By affecting these nerve endings the entire nerve's ability to transmit pain is reduced. This novel mechanism of action has been observed when Civamide Nasal Spray is applied to the nasal mucosa in subjects with headache disorders mediated by the [TN], e.g. migraine headaches and cluster headaches with resulting decreases in headache pain and frequency. This study is a 9 week, double-blind, vehicle-controlled study of adult subjects that have moderate to severe pain (a minimum of an average pain score of 4 on a 0-10 point scale) due to PHN of the [TN] for at least 12 months. The study is composed of a 1-week non-treatment Baseline Period during which subjects will be required to complete a daily diary assessing overall pain and sleep interference. The 1 week Baseline Period will be followed by a 6 week Double-Blind Treatment Period and a 2 week Observation Period. Subjects will be randomized 1:1, approximately [20] subjects per group. The primary outcome variable will be the change in the Average Daily PHN Pain Score from the Baseline Period to the last week of the Treatment Period. Adverse events will be recorded during the study.
PHN of the trigeminal nerve is a condition primarily affecting the elderly,3,4,5 who are usually on other medications for other medical problems from which they suffer. Thus, the availability of an effective medication for PHN of the trigeminal nerve, such as Civamide Nasal Spray, that is not systemically absorbed, [as demonstrated in a pharmacokinetic study13], and consequently is without both systemic adverse effects as well as drug-drug interactions [of available systemic medications] would represent a significant improvement in the treatment of this disease in this population.
