The project which is the subject of this grant application is a Phase 3 clinical study to demonstrate safety and efficacy of Naloxone 0.5% Hydrochloride (HCl) Lotion for the relief of pruritus associated with [the] mycosis fungoides (MF) [as well as Szary syndrome (SS), both being] form[s] of cutaneous t-cell lymphoma (CTCL). The seriousness of pruritus (itch) that accompanies skin disorders such as MF, the most prevalent subtype of CTCL, is often underestimated. Severe chronic pruritus has clinically significant effects on morbidity and mortality that impact clinical management of the disease its costs. As a symptom, itch is uncomfortable and annoying, distracts and disrupts activities of daily life, interferes with sleep, and may affect social interactive behavior. Moreover, chronic pruritus has been associated with considerable impairment of quality of life comparable to chronic pain.1 The mortality rate in patients with MF is estimated to be twice as frequent in patients with itching than in those without itching.2 Current medications do not completely address the pruritus associated with MF which leads to infections from excoriations. Naloxone 0.5% HCl Lotion will fill this unmet medical need. Traditional anti-pruritic drugs, i.e. antihistamines, tricyclic antidepressants, and corticosteroids, are not generally effective in managing the itch associated with MF.11 Current evidence suggests that MF related pruritus may be mediated by a peripheral opinergic pathway and provides the scientific rationale for treating MF related pruritus with the opioid antagonist. Naloxone is classified pharmacologically as an opioid antagonist with activity at multiple opioid receptors including Mu, Delta, Kappa1 and Kappa3.3 The treatment of pruritus associated with MF using a topical formulation of naloxone represents a novel therapeutic approach [as systemic administration is not practical due to the short half life of naloxone in blood.] This is a 6 ? 9 week, double-blind, vehicle-controlled, crossover study of approximately 160 adult subjects that have moderate to severe pruritus (a minimum score of 5 on the 0 ? 10 point scale) associated with MF [or SS]. The study is composed of a 1 week non-treatment Screening Period during which subjects will be required to complete a daily diary assessing overall pruritus. The 1 week Screening Period is followed by a two week Treatment Period, 4 ? 28 day Washout Period, and another two week Treatment Period. Subjects will be randomized 1:1 to receive either Naloxone 0.5% HCl Lotion or Vehicle Lotion in the first Treatment Period, and the other in the second Treatment Period. The primary efficacy variable will be the change from Baseline in the weekly average of the 11-point Numeric Rating Scale (NRS) for Pruritus assessed at Day 14 of each Treatment Period. The planned duration of the Phase 3 study is approximately 2 years. Following this Phase 3 study, Elorac, Inc. will conduct a 6 month safety study to complete and submit a NDA to the US FDA. Six Phase 1 studies4,5,6,7,8,9 and a Phase 2 safety and efficacy trial in 15 subjects with MF or SS10 have already been completed. Naloxone Lotion for the topical treatment of pruritus associated with MF was granted orphan status by the FDA on November 23, 2010 and fast track designation on April 11, 2013.
Completing the Phase 3 safety and efficacy study is an essential step in the path toward obtaining FDA approval for the use of Naloxone 0.5% HCl Lotion to relieve pruritus associated with mycosis fungoides (MF). [and Szary syndrome (SS)]. There currently is no cure for MF [or SS]. Unfortunately, traditional drugs to alleviate itching, i.e., the systemic antihistamines, corticosteroids, doxepin, are generally ineffective in relieving pruritus in MF [and SS].11 New safe and effective treatments for the alleviation of pruritus, such as Naloxone 0.5% HCl Lotion, could prove most beneficial in the management of patients with MF [and SS] by reducing or eliminating the severity of pruritus in the early stages of MF [and SS] and therefore avoiding the morbidity and mortality associated with infections secondary to pruritus-related excoriation, as well as the negative impact of quality of life associated with intractable, chronic pruritus.