Clinical Trials /

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

NCT02811783

Description:

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

Related Conditions:
  • Mycosis Fungoides
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
  • Sezary Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Naloxone Hydrochloride Study for Relief of Pruritus in Patients With MF or SS Forms of CTCL
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: EL-1007-01-01
  • SECONDARY ID: 1R01FD005396-01A1
  • NCT ID: NCT02811783

Conditions

  • Mycosis Fungoides
  • Lymphoma, T-Cell, Cutaneous
  • Sézary Syndrome

Interventions

DrugSynonymsArms
Naloxone Hydrochloride Lotion, 0.5%Naloxone Hydrochloride Lotion, 0.5%
Placebo LotionPlacebo Lotion

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Naloxone Hydrochloride Lotion, 0.5%Active ComparatorNaloxone Hydrochloride Lotion 0.5%
  • Naloxone Hydrochloride Lotion, 0.5%
Placebo LotionPlacebo ComparatorPlacebo Lotion
  • Placebo Lotion

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Numeric Rating Scale (NRS) for Pruritus
Time Frame:Baseline and 2 Weeks
Safety Issue:
Description:Change from Baseline to Day 14 in average NRS for Pruritus for each Treatment Period

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure:Numeric Rating Scale for Sleep
Time Frame:Baseline and 1 and 2 weeks
Safety Issue:
Description:The change from Baseline at each week of the NRS for Sleep average score for each Treatment Period.
Measure:Numeric Rating Scale for Pruritus
Time Frame:Baseline and 1 week
Safety Issue:
Description:The change from Baseline at Week 1 of the NRS for Pruritus average score for each Treatment Period.
Measure:Categorical Rating Scale (CRS) for Skin Integrity
Time Frame:Baseline and 2 weeks
Safety Issue:
Description:The change from Baseline at Week 2 of the CRS for Skin Integrity for each Treatment Period.
Measure:Pruritus Quality of Life Score (PQOL)
Time Frame:Baseline and Day 14 of each Treatment period
Safety Issue:
Description:The change from Baseline in the final categorization of the PQOL at Day 14 of each Treatment Period

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Elorac, Inc.

Trial Keywords

  • Pruritus
  • Mycosis Fungoides
  • CTCL
  • naloxone
  • opiate antagonist
  • Sézary Syndrome

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