Dose-Tolerability Titration Study to Evaluate The Efficacy And Safety Of Perampanel (E2007) In Patients With Post-Herpetic Neuralgia (PHN)
Condition: Neuralgia
MeSH terms: Neuralgia; Neuralgia, Postherpetic
Intervention: E2007 (perampanel); Placebo
Intervention description: 2 mg titrated up to 8 mg maximum; taken once daily.; 2 mg titrated up to 8 mg maximum; taken once daily.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 146.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Post-Herpetic Neuralgia; PHN)

Summary:

      The purpose of the study is to determine the efficacy and safety of Perampanel (E2007) in
      patients with Post-Herpetic Neuralgia (PHN).
    

Eligibility criteria:

        Inclusion Criteria:

        To be included, patients must meet the following:

          1. Provide written informed consent, prior to entering the study or undergoing any study
             procedures.

          2. Male and female patients ≥18 years of age. Females should be either of nonchildbearing
             potential as a result of surgery or menopause (1 year after onset), or of childbearing
             potential and practicing a medically acceptable method of contraception. Acceptable
             contraception includes: abstinence, a barrier method plus spermicide, or intrauterine
             device [IUD]. Those females using hormonal contraceptives must also be using an
             additional approved method of contraception (e.g., a barrier method plus spermicide or
             IUD). Contraceptive use must start at least 1 month before Visit 1, be practiced
             throughout the entire study period, and continue for 1 month after the end of the
             study. They must also have a negative serum beta-human chorionic gonadotropin (β-hCG)
             at Visit 1, and a negative urine pregnancy test at Baseline Visit 2.

          3. PHN of at least 6 months duration; the onset of PHN is defined as the time from
             healing of herpes zoster skin lesions.

          4. Pain over the past 6 months, and not in a clinically identifiable improving or
             worsening trend, based on medical history.

          5. Score of ≥ 40 mm on the visual analog scale (VAS) of the short form McGill Pain
             Questionnaire (SF-MPQ) at both Visit 1 and Baseline (Visit 2 prior to randomization).

          6. Have completed the patient diary for at least 6 of the 7 days prior to Visit 2
             (Baseline).

          7. Average daily pain score of ≥ 4, on 11-point Likert scale during the 7 days prior to
             randomization [from the diaries].

          8. Reliable and willing and able to cooperate with all study procedures, including the
             following examples:

               -  Accurately entering the diary on a daily basis

               -  Returning for study visits on the required dates

               -  Accurately and reliably reporting symptoms (including treatment-emergent signs
                  and symptoms)

               -  Taking study drug as required by protocol

          9. Be on stable analgesic treatment (same medication(s)) or stable nonpharmacological
             pain treatment for at least 4 weeks prior to Visit 1 and remain on this stable
             treatment throughout the study. Nonpharmacologic pain treatment includes the
             following:

               -  relaxation/hypnosis

               -  physical or occupational therapy

               -  mental-health counseling

               -  acupuncture

               -  injections

               -  blocks, etc.

               -  Episodic or periodic pharmacologic treatments such as monthly injections for
                  treatment of pain (eg, local anesthetics) will not be permitted.

               -  Up to 4 g of acetaminophen/day is permitted as rescue medication, as needed,
                  during the trial.

        Exclusion Criteria:

        Patients with any of the following are to be excluded:

          1. Any condition that could interfere with the conduct of the trial or confound efficacy
             evaluations including the following examples: pain or neuropathy from another cause
             (including painful diabetic neuropathy), such as central pain, radiculopathy, painful
             arthritis, etc.

          2. Motivation by secondary gain, or where there is a negative-incentive to achieving pain
             and functional relief (eg, litigation). This will be determined from the medical
             history and is at the discretion of the investigator.

          3. Inability to cooperate with protocol, for any reason.

          4. Clinically significant, progressive, or potentially unstable disease of any body
             system including cardiovascular, gastrointestinal, CNS, psychiatric, endocrine, or
             immunologic, including patients with any of the following broad disease categories:

               1. Systemic infections (eg, human immunodeficiency virus [HIV], hepatitis,
                  tuberculosis [TB], syphilis); lack of appropriate medical history of these
                  conditions is acceptable,

               2. History of past (within the past 12 months) or present drug or alcohol abuse as
                  per the Diagnostic and Statistical Manual - 4th Edition (DSM IV) criteria,

               3. History of acute coronary syndrome within the past 12 months,

               4. Active cancer within the previous 5 years (the exception is fully treated,
                  non-melanoma skin cancer such as basal cell carcinoma),

               5. Systemic chemotherapy or immunotherapy within the past 5 years,

               6. History of major depression, bipolar disease, psychosis or suicidal ideation or
                  attempts within the past 5 years,

               7. History of major systemic allergy such as anaphylactoid reactions or
                  Stevens-Johnson syndrome (however, patients with limited allergies such as
                  contact dermatitis or minor allergy to penicillin are acceptable).

          5. Any of the following laboratory abnormalities at Visit 1:

               1. Clinically significant ECG abnormality, including prolonged QTc (defined as QTcB
                  > 450 msec),

               2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 times
                  the upper limit of normal (ULN),

               3. Clinically significant abnormal white blood cell (WBC), absolute neutrophil, or
                  platelet count values,

               4. Any other clinically significant laboratory value.

          6. Exposure to an investigational drug within the 30 days prior to Visit 1 or exposure
             ever to perampanel.

          7. Females who are pregnant, lactating, or planning to become pregnant during the study.

          8. Use of any medication known to be a strong inducer of CYP3A4 activity within 4 weeks
             prior to Visit 1; use of CYP3A4 inducers is prohibited for the entire study duration.