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

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

Official Title
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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)

Conditions
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Neuralgia

Intervention / Treatment
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* Drug: E2007 (perampanel)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Cohort 1<br> | Drug: Placebo<br>* 2 mg titrated up to 8 mg maximum; taken once daily.<br>|
| Experimental: Perampanel Cohort 1, 3-week Titration<br> | Drug: E2007 (perampanel)<br>* 2 mg titrated up to 8 mg maximum; taken once daily.<br>* Other names: perampanel;|
| Experimental: Placebo Cohort 2<br> | Drug: Placebo<br>* 2 mg titrated up to 8 mg maximum; taken once daily.<br>|
| Experimental: Perampanel Cohort 2, 1-week Titration<br> | Drug: E2007 (perampanel)<br>* 2 mg titrated up to 8 mg maximum; taken once daily.<br>* Other names: perampanel;|
| Experimental: Perampanel Cohort 2, 2- Week Titration<br> | Drug: E2007 (perampanel)<br>* 2 mg titrated up to 8 mg maximum; taken once daily.<br>* Other names: perampanel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Pain Scores to Week 15/ End of Treatment (EOT) (Including Modified BOCF Data) | Average pain scores are based on pain intensity (11-point Likert-type numerical scale, where 0=no pain and 10=worst possible pain), reported by the subjects in a daily diary. The average pain score for baseline was calculated using the average of the last 7 scores prior to randomization, and the average pain score for Week 15 was computed using the average of the last 7 on-treatment scores prior to Week 15, and they were reported by treatment group. | Baseline and Week 15 | 
| Responder Rate: Subjects With at Least 30 Percent Reduction in Pain | A responder was a participant with at least 30 percent reduction in average pain scores, using modified BOCF, based on pain intensity (11-point Likert-type numerical scale where 0=no pain and 10=worst possible pain), reported by the subjects in a daily diary. The average pain score for baseline was calculated using the average of the last 7 scores prior to randomization, and the average pain score for Week 15 was computed using the average of the last 7 on-treatment scores prior to Week 15, and they were reported by treatment group. | Baseline and Week 15 | 
| Responder Rate: Subjects With at Least 50 Percent Reduction in Pain | A responder was a participant with at least 50 percent reduction in average pain scores, using modified BOCF, based on pain intensity (11-point Likert-type numerical scale where 0=no pain and 10=worst possible pain), reported by the subjects in a daily diary. The average pain score for baseline was calculated using the average of the last 7 scores prior to randomization, and the average pain score for Week 15 was computed using the average of the last 7 on-treatment scores prior to Week 15, and they were reported by treatment group. | Baseline and Week 15 | 
| Change From Baseline in Average Pain Scores by Week | Change from baseline in average pain scores by week based on pain intensity (11-point Likert-type numerical scale where 0=no pain and 10=worst possible pain), reported by the subjects in a daily diary. The average pain scores were calculated as the average of available scores in each week, and were reported by treatment group. | Week 1 through Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 15/EOT in Average Sleep Interference Scores | The average of the last 7 available sleep scores prior to the visit, based on the 11-point Likert-type numerical rating scale for sleep interference (where 0=pain did not interfere with sleep, to 10=pain completely interfered with sleep [unable to sleep]), and they were reported by treatment group. | Baseline and Week 15 | 
| Patient Global Impression of Change (PGIC) at Week 15/EOT | Changes were calculated using the modified BOCF method | Week 15 | 
| Clinician Global Impression of Change (CGIC) at Week 15/EOT | Changes were calculated using the modified BOCF method | Week 15 | 
| Change From Baseline to Week 15/EOT in HADS Anxiety Subscale Scores (Modified BOCF) | The HADS (Hospital Anxiety and Depression Scale) is a widely used, self-reported, 14-item instrument that measures the presence and severity of anxiety and depression. It consists of 2 subscales; a 7-item anxiety subscale (HADS-A) and a 7-item depression subscale (HADS-D). HADS-A consists of a 7-item scale, each scored on a 4-pt scale (0, 1, 2, or 3), where a higher score indicates worse anxiety. Range of possible HADS anxiety subscale scores is 0 to 21, and normal=(0-7), mild=(8-10), moderate=(11-14), and severe=(15-21). | Baseline and Week 15 | 
| Change From Baseline to Week 15/EOT in HADS Depression Subscale Scores (Modified BOCF) | The HADS (Hospital Anxiety and Depression Scale) is a widely used, self-reported, 14-item instrument that measures the presence and severity of anxiety and depression. It consists of 2 subscales; a 7-item anxiety subscale (HADS-A) and a 7-item depression subscale (HADS-D). HADS-D consists of a 7-item scale, each scored on a 4-pt scale (0, 1, 2, or 3), where a higher score indicates worse depression. Range of possible HADS depression subscale scores is 0 to 21, and normal=(0-7), mild=(8-10), moderate=(11-14), and severe=(15-21). | Baseline and Week 15 | 
| Analysis of Allodynia (Present/Not Present) at Week 15/EOT- by Treatment Groups ITT Population (Modified BOCF) | Allodynia is defined as a painful reaction to a non-painful stimulus. | Week 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-Herpetic Neuralgia, PHN)