A double-blind, randomized, vehicle controlled, crossover study to evaluate the safety and efficacy of topical naloxone hydrochloride lotion, 0.5%, for the relief of pruritus in patients with the mycosis fungoides (MF) form of cutaneous t-cell lymphoma (CTCL)
The primary objective is to evaluate the safety and efficacy of topically applied naloxone lotion, 0.5%, for the treatment of pruritus in patients with the mycosis fungoides (MF) or Sézary syndrome (SS) Forms of Cutaneous Tcell Lymphoma (CTCL).
• Signed informed consent has been obtained.
• Subject is at least 21 years of age.
• Diagnosis of mycosis fungoides (MF) or Sézary syndrome (SS) will be based on a combination of histological, clinical, and immunophenotypical criteria. The histological criteria will be based on skin biopsy from the most representative skin area. The diagnostic criteria used for each subject will be specified in the case report forms and the specific classification of MF or SS will be identified. The TNMB system will be used to classify the stage of disease (See Section 8.4 for details).
• Completion of the mSWAT assessment.
• A history of pruritus that meets following criteria: At Screening Day -7:
• present on a daily basis for greater than one month prior to Screening Day -7,
• NRS for Pruritus score ≥5 as rated by the subject at the Day -7 Visit. Note: If the score is <5 and subject is taking or has taken a medication which may be affecting pruritus (e.g. systemic antihistamine or topical steroid), and if Investigator and subject agree, subject may washout or continue washout of medication and return for Day -7 Visit procedures after washout. At Baseline Period 1 Day 0:
• NRS for Pruritus score of at least 5 recorded in the subject diary on at least 4 of the 7 days preceding Baseline Period 1 Day 0.
• Pruritic treatment area of 5-95% of the subject's total treatable body surface area.
• Subject can be expected to reliably follow treatment instructions and visit schedule.
• Non-pregnant, non-lactating females of childbearing potential who agree to use medically acceptable forms of birth control (abstinence, hormonal contraceptives, diaphragm with spermicide, condom with spermicide, or intrauterine device) throughout the study or females of non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal ligation] or post-menopausal ≥ 1 year). A negative urine pregnancy test must be confirmed at Baseline screening for all female subjects who are not post-menopausal > 1 year or surgically sterile.
• The subject agrees not to begin any new concomitant medications during their participation in the study, with the exception of medications necessary to treat infection, and to continue any concomitant medication throughout the study.
• Subject has no visual or motor impairments that will make it difficult to complete the Daily Diary or apply the study medication.
• Subject is able to speak, read, and write English and agrees to participate and comply with the study procedures.
• Subject has a body mass index (BMI) between 18.5 and 30.5 kglm2 (see Appendix C, Body Mass Index Table) (subjects in PK subset only).
• Pregnant or lactating female.
• History of clinically significant heart failure.
• Myocardial infarction within the past six months.
• A history of ventricular arrhythmia requiring treatment.
• Any medical condition which would, in the Investigator's opinion, preclude the subject from successfully participating in the study.
• A known allergy to naloxone hydrochloride or any excipient in the formulation.
• Previous naloxone use for pruritus.
• Positive urine drug screen at Day 0 for opiates. Positive urine drug screen for anything other than opiates not explained, e.g., by concomitant medication, would also exclude the subject.
• Treatment with any of the following during the restricted time period prior to Day -7, and at any time during the study, is not allowed: Medication/Treatment Restriction: Systemic narcotic analgesics (e.g. morphine, codeine) 7 days, Topical antihistamines to any skin surface [e.g. Zonalon® (doxepin)] 7 days, Other investigational drugs (excluding any therapies for the treatment of MF or SS) 30 days
Drug: Naloxone Hydrochloride Lotion, 0.5%, Drug: Placebo Lotion
Mycosis Fungoides, Lymphoma, T-Cell, Cutaneous, Sézary Syndrome
Pruritus, Mycosis Fungoides, CTCL, naloxone, opiate antagonist, Sézary Syndrome, Clinics and Surgery Center (CSC)