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

Tracking Information
First Submitted Date ICMJE	June 15, 2016
First Posted Date ICMJE	June 23, 2016
Last Update Posted Date	November 15, 2018
Actual Study Start Date ICMJE	January 2017
Estimated Primary Completion Date	June 2021 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 22, 2016)	Numeric Rating Scale (NRS) for Pruritus [ Time Frame: Baseline and 2 Weeks ]; Change from Baseline to Day 14 in average NRS for Pruritus for each Treatment Period
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT02811783 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 26, 2017)	Responder Analysis - The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. [ Time Frame: Baseline and 2 Weeks ]The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. A clinically significant improvement is defined as an improvement of at least one category on the 4-point (none, mild, moderate, severe) Likert Scale verbal rating scale (VRS) and at least two points on the 11-point NRS for Pruritus. The NRS for Pruritus scores will be converted to VRS scores as follows for the analysis: 0=none, 1-3=mild, 4-6=moderate, and 7-10=severe.; Numeric Rating Scale for Sleep [ Time Frame: Baseline and 1 and 2 weeks ]The change from Baseline at each week of the NRS for Sleep average score for each Treatment Period.; Numeric Rating Scale for Pruritus [ Time Frame: Baseline and 1 week ]The change from Baseline at Week 1 of the NRS for Pruritus average score for each Treatment Period.; Categorical Rating Scale (CRS) for Skin Integrity [ Time Frame: Baseline and 2 weeks ]The change from Baseline at Week 2 of the CRS for Skin Integrity for each Treatment Period.; Pruritus Quality of Life Score (PQOL) [ Time Frame: Baseline and Day 14 of each Treatment period ]The change from Baseline in the final categorization of the PQOL at Day 14 of each Treatment Period
Original Secondary Outcome Measures ICMJE; (submitted: June 22, 2016)	Responder Analysis - The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. [ Time Frame: Baseline and 2 Weeks ]The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. A clinically significant improvement is defined as an improvement of at least one category on the 4-point (none, mild, moderate, severe) Likert Scale verbal rating scale (VRS) and at least two points on the 11-point NRS for Pruritus. The NRS for Pruritus scores will be converted to VRS scores as follows for the analysis: 0=none, 1-3=mild, 4-6=moderate, and 7-10=severe.; Numeric Rating Scale for Sleep [ Time Frame: Baseline and 1 and 2 weeks ]The change from Baseline at each week of the NRS for Sleep average score for each Treatment Period.; Numeric Rating Scale for Pruritus [ Time Frame: Baseline and 1 week ]The change from Baseline at Week 1 of the NRS for Pruritus average score for each Treatment Period.; Categorical Rating Scale (CRS) for Skin Integrity [ Time Frame: Baseline and 2 weeks ]The change from Baseline at Week 2 of the CRS for Skin Integrity for each Treatment Period.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Naloxone Hydrochloride Study for Relief of Pruritus in Patients With MF or SS Forms of CTCL
Official Title ICMJE	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 MF or SS Forms of Cutaneous T-Cell Lymphoma
Brief Summary	This multi-center, double-blind, vehicle-controlled, randomized crossover design study will 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 T-cell Lymphoma (CTCL). This study will also determine if there is systemic absorption of the drug in a subset of subjects and if so, describe the range and mean plasma levels reached after two weeks of three time daily (TID) dosing. Funding Source - FDA OOPD
Detailed Description	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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Sézary Syndrome
Intervention ICMJE	Drug: Naloxone Hydrochloride Lotion, 0.5% Topical TID for 2 weeks; Drug: Placebo Lotion Topical TID for 2 weeks
Study Arms	Active Comparator: Naloxone Hydrochloride Lotion, 0.5% Naloxone Hydrochloride Lotion 0.5% Intervention: Drug: Naloxone Hydrochloride Lotion, 0.5%; Placebo Comparator: Placebo Lotion Placebo Lotion Intervention: Drug: Placebo Lotion
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: June 22, 2016)	160
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	August 2021
Estimated Primary Completion Date	June 2021 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: All subjects must meet the following criteria for admission into the study: 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). Exclusion Criteria: Subjects meeting any of the following criteria will be excluded from study participation: 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
Sex/Gender	Sexes Eligible for Study: All
Ages	21 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact: Scott B Phillips, MD 8473628200 scott@eloracpharma.com Contact: Heidi Fezatte, BS 8473628200 hfezatte@eloracpharma.com
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT02811783
Other Study ID Numbers ICMJE	EL-1007-01-01; 1R01FD005396-01A1 ( U.S. FDA Grant/Contract )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Plan to Share IPD: No
Responsible Party	Elorac, Inc.
Study Sponsor ICMJE	Elorac, Inc.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Scott B Phillips, MD Elorac, Inc.
PRS Account	Elorac, Inc.
Verification Date	November 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP