Naloxone Hydrochloride Study for Relief of Pruritus in Patients With MF or SS Forms of CTCL

There will be 160 subjects enrolled in the study. The study consists of a Screening Period of
up to 7 days during which inclusion / exclusion criteria will be reviewed. Subjects meeting
inclusion / exclusion criteria including the diagnostic criteria for MF or SS and a score of
at least 5 on the 11-Point Numeric Rating Scale (NRS) for Pruritus will complete the one week
Screening Period. Subjects will complete a daily diary for NRS for Pruritus scores and Sleep
scores. At the end of the Screening Period, subjects who have a NRS for Pruritus score of at
least 5 recorded in the diary on at least 4 of the 7 days preceding Day 0 will be eligible to
continue. Baseline assessments will be recorded for vital signs, pruritic body surface area,
skin integrity, PQOL, and laboratory results. The Baseline period will be followed by a 2
week Treatment Period 1 in which subjects will be randomized to Naloxone Lotion 0.5% or
Placebo Lotion to be applied TID for 14 days. During the 2 week Treatment Period subjects
will complete daily diaries of NRS for Pruritis scores and Sleep scores. On Day 14 subjects
will return to the clinic to review diaries, adverse events (AEs), concomitant medications,
and to record body surface area for pruritus, skin integrity, PQOL, and laboratory results.
Subjects will then enter a Washout Period for up to 56 days until the subject again scores at
least 5 on the NRS for Pruritus on 4 consecutive or 4 of the past 7 days or 56 days pass.
Subjects will then enter a 2 week Treatment Period 2 during which the same procedures as
Treatment Period 1 will be performed except subjects will receive the alternate treatment to
that assigned in Treatment Period 1.

Inclusion Criteria:

All subjects must meet the following criteria for admission into the study:

1. Signed informed consent has been obtained.

2. Subject is at least 21 years of age.

3. 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).

4. Completion of the mSWAT assessment.

5. 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.

6. Pruritic treatment area of 5-95% of the subject's total treatable body surface area.

7. Subject can be expected to reliably follow treatment instructions and visit schedule.

8. 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.

9. 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.

10. Subject has no visual or motor impairments that will make it difficult to complete the
Daily Diary or apply the study medication.

11. Subject is able to speak, read, and write English and agrees to participate and comply
with the study procedures.

12. 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).

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from study participation:

1. Pregnant or lactating female.

2. History of clinically significant heart failure.

3. Myocardial infarction within the past six months.

4. A history of ventricular arrhythmia requiring treatment.

5. Any medical condition which would, in the Investigator's opinion, preclude the subject
from successfully participating in the study.

6. A known allergy to naloxone hydrochloride or any excipient in the formulation.

7. Previous naloxone use for pruritus.

8. 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.

9. 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