Clinical trial NCT00592774: Dose-Tolerability Titration Study to Evaluate The Efficacy And Safety Of Perampanel (E2007) In Patients With Post-Herpetic Neuralgia (PHN)
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Tolerability Titration Study To Evaluate The Efficacy And Safety Of Perampanel (E2007) In Patients With Post-Herpetic Neuralgia (PHN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuralgia
Keywords: Post-Herpetic Neuralgia
PHN)
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2008-01-14
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline in Average Pain Scores to Week 15/ End of Treatment (EOT) (Including Modified BOCF Data)
timeFrame: Baseline and Week 15
measure: Responder Rate: Subjects With at Least 30 Percent Reduction in Pain
timeFrame: Baseline and Week 15
measure: Responder Rate: Subjects With at Least 50 Percent Reduction in Pain
timeFrame: Baseline and Week 15
measure: Change From Baseline in Average Pain Scores by Week
timeFrame: Week 1 through Week 16
Secondary outcomes:
measure: Change From Baseline to Week 15/EOT in Average Sleep Interference Scores
timeFrame: Baseline and Week 15
measure: Patient Global Impression of Change (PGIC) at Week 15/EOT
timeFrame: Week 15
measure: Clinician Global Impression of Change (CGIC) at Week 15/EOT
timeFrame: Week 15
measure: Change From Baseline to Week 15/EOT in HADS Anxiety Subscale Scores (Modified BOCF)
timeFrame: Baseline and Week 15
measure: Change From Baseline to Week 15/EOT in HADS Depression Subscale Scores (Modified BOCF)
timeFrame: Baseline and Week 15
measure: Analysis of Allodynia (Present/Not Present) at Week 15/EOT- by Treatment Groups ITT Population (Modified BOCF)
timeFrame: Week 15
Other outcomes:
Locations:
city: Peoria
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Boulder
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Milford
country: United States
state: Connecticut
city: Boca Raton
country: United States
state: Florida
city: Bradenton
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Delray Beach
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Ft. Lauderdale
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Largo
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Naples
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Palm Beach Gardens
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: St. Petersburg
country: United States
state: Florida
city: Sunrise
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
facility: Pain and Rehabilitation Clinic of Chicago
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Towson
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: West Yarmouth
country: United States
state: Massachusetts
city: Southfield
country: United States
state: Michigan
city: Missoula
country: United States
state: Montana
city: Las Vegas
country: United States
state: Nevada
city: Brooklyn
country: United States
state: New York
city: High Point
country: United States
state: North Carolina
city: Winston Salem
country: United States
state: North Carolina
city: Kettering
country: United States
state: Ohio
city: Bensalem
country: United States
state: Pennsylvania
city: Norristown
country: United States
state: Pennsylvania
city: Warwick
country: United States
state: Rhode Island
city: Dallas
country: United States
state: Texas
city: Kelowna
country: Canada
state: British Columbia
city: Sarnia
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Pointe Claire
country: Canada
state: Quebec
city: Saskatoon
country: Canada
state: Saskatchewan
Study officials:
affiliation: Eisai Inc.
name: Allison Mann, MD
role: STUDY_DIRECTOR
References: