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

Eisai

Status and phase: Completed; Phase 2

Conditions: Neuralgia

Treatments: Drug: E2007 (perampanel); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00592774

E2007-A001-218

Details and patient eligibility

About

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

Enrollment: 146 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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146 participants in 5 patient groups, including a placebo group

Placebo Cohort 1

Placebo Comparator group

Treatment:

Drug: Placebo

Perampanel Cohort 1, 3-week Titration

Experimental group

Treatment:

Drug: E2007 (perampanel)

Placebo Cohort 2

Experimental group

Treatment:

Drug: Placebo

Perampanel Cohort 2, 1-week Titration

Experimental group

Treatment:

Drug: E2007 (perampanel)

Perampanel Cohort 2, 2- Week Titration

Experimental group

Treatment:

Drug: E2007 (perampanel)