Dose-Tolerability Titration Study to Evaluate The Efficacy And Safety Of Perampanel (E2007) In Patients With Post-Herpetic Neuralgia (PHN)

Inclusion criteria

To be included, patients must meet the following:

• Provide written informed consent, prior to entering the study or undergoing any study procedures.
• 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.
• PHN of at least 6 months duration; the onset of PHN is defined as the time from healing of herpes zoster skin lesions.
• Pain over the past 6 months, and not in a clinically identifiable improving or worsening trend, based on medical history.
• 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).
• Have completed the patient diary for at least 6 of the 7 days prior to Visit 2 (Baseline).
• Average daily pain score of ≥ 4, on 11-point Likert scale during the 7 days prior to randomization [from the diaries].
• 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
• 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:

• 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.
• 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.
• Inability to cooperate with protocol, for any reason.
• 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:

• Systemic infections (eg, human immunodeficiency virus [HIV], hepatitis, tuberculosis [TB], syphilis); lack of appropriate medical history of these conditions is acceptable,
• 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,
• History of acute coronary syndrome within the past 12 months,
• Active cancer within the previous 5 years (the exception is fully treated, non-melanoma skin cancer such as basal cell carcinoma),
• Systemic chemotherapy or immunotherapy within the past 5 years,
• History of major depression, bipolar disease, psychosis or suicidal ideation or attempts within the past 5 years,
• 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).
• Any of the following laboratory abnormalities at Visit 1:

• Clinically significant ECG abnormality, including prolonged QTc (defined as QTcB > 450 msec),
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 times the upper limit of normal (ULN),
• Clinically significant abnormal white blood cell (WBC), absolute neutrophil, or platelet count values,
• Any other clinically significant laboratory value.
• Exposure to an investigational drug within the 30 days prior to Visit 1 or exposure ever to perampanel.
• Females who are pregnant, lactating, or planning to become pregnant during the study.
• 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.