Study to Assess the Efficacy, Safety, and Tolerability of ADL5747 in Participants With Postherpetic Neuralgia
Condition: Postherpetic Neuralgia
MeSH terms: Neuralgia; Neuralgia, Postherpetic
Intervention: ADL5747; Placebo; Pregabalin
Intervention MeSH terms: Pregabalin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: pain; delta opioid receptor agonist

Summary:

      The primary purpose of this study is to evaluate the analgesic efficacy of ADL5747 in
      participants with postherpetic neuralgia (PHN). The secondary objective of this study is to
      evaluate the safety, tolerability, and pharmacokinetics of ADL5747.
    

Eligibility criteria:

        Key inclusion Criteria:

          -  have a diagnosis of PHN (defined as pain present for at least 3 months after the
             healing of herpes zoster rash; there is no upper limit on the duration of PHN)

          -  have an average daily pain score of at least 4 on the numeric pain rating scale (0-10)
             at the start of baseline week for Treatment Period 1 (Day -7) through the start of the
             first week of Treatment Period 1 (Day 1)

          -  be willing and able to understand and comply with protocol requirements, dietary and
             dosing regimens, and other protocol instructions and restrictions (for example, forgo
             use of their normal pain medication and other protocol specified prohibited
             medications for the duration of the study)

          -  for male participants, be surgically sterile or agree to use an appropriate method of
             contraception or have a sexual partner who is surgically sterile or using an
             insertable, injectable, transdermal, or combination oral contraceptive approved and
             deemed highly effective by the United States Food and Drug Administration (FDA) from
             the first dose of study medication through 30 days after the last dose of study
             medication on Day 49

          -  for female participants of childbearing potential, be using an insertable, injectable,
             transdermal, or combination oral contraceptive approved and deemed highly effective by
             the FDA from the first dose of study medication through 30 days after the last dose of
             study medication on Day 49 and have negative results on a serum pregnancy test during
             the start of the screening period to obtain informed consent and determine eligibility
             for the study (Day -37 to -14) and on a urine pregnancy test during the start of the
             first week of Treatment Period 1 (Day 1) (women who are surgically sterile [for
             example, hysterectomy, tubal ligation] or postmenopausal [if ≥ 55 years old, no menses
             for at least 2 years; if < 55 years old, follicle stimulating hormone concentrations
             within the postmenopausal range of > 40 milli-International Units per milliliter
             (mIU/mL) and 17 β estradiol levels of < 37 picograms per milliliter (pg/mL)] are also
             eligible to participate)

        Key Exclusion Criteria:

          -  be pregnant or lactating

          -  have significant skin lesions that could interfere with pain assessment

          -  have a history of seizures or a history of abnormal electroencephalographic results at
             any time (participants with a history of febrile seizures before the age of 6 years
             may be enrolled)

          -  have had previous neurolytic or neurosurgical therapy for PHN

          -  have had a treatment that included local anesthetic nerve blocks within 30 days before
             the start of the baseline week for Treatment Period 1 (Day -7)

          -  have any other type of pain that may impair the self-assessment of pain due to PHN

          -  have, as determined by the investigator or the sponsor's medical monitor, a history or
             clinical manifestations of significant renal, hepatic, hematologic, cardiovascular,
             metabolic, gastrointestinal, neurologic, psychiatric, or other condition that would
             preclude participation in the study

          -  have an active malignancy of any type (participants with a history of successfully
             treated malignancy > 5 years before the scheduled first dose of study medication and
             participants with treated basal or squamous cell cancer may be enrolled)

          -  have a medical history or condition that may interfere with drug absorption (for
             example, stomach resection)

          -  be currently using protocol specified prohibited medications in the absence of
             appropriate washout

          -  be currently taking moderate or strong inhibitors or inducers of cytochrome P450-3A
             (CYP3A) or inhibitors of P glycoprotein transporters

          -  have an estimated glomerular filtration rate (GFR) that is less than or equal to 60
             mL/min calculated by the Cockcroft Gault equation or have alanine aminotransferase
             and/or aspartate aminotransferase levels that are at least 2 times the upper limit of
             normal

          -  have a history of substance abuse or dependence within the previous 5 years, including
             alcohol or positive results on the urine drug screen at start of screening period,
             start of baseline week, or start of the first week of Treatment Period 1 (Day -37 to
             Day 1); participants may be enrolled if positive results are due to medication(s)
             prescribed for the participant and permitted by the protocol

          -  have a history of suicide attempts or be judged clinically to be at serious risk of
             suicide

          -  have a score of more than 29 on the Beck Depression Inventory-II at start of screening
             period (Day -37 to Day -14)

          -  have a history of allergy to acetaminophen (the rescue medication for this study)

          -  have a history of intolerance to pregabalin or documented failure to respond to a
             maximally tolerated dose of pregabalin

          -  have ever received the investigational drug ADL5747 or have participated in any
             clinical study involving an investigational product in which they received that
             product within 30 days before the scheduled administration of study medication for
             this study