A Study Assessing Efficacy of Brivaracetam in Subjects With Persistent Pain After Shingles (Post-herpetic Neuralgia)

Study Overview
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Brief Summary
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Study will assess efficacy, safety and tolerability of brivaracetam in post-herpetic neuralgia (PHN). Duration of 7 weeks divided into 3 periods with no up-titration, nor down-titration.

Official Title
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An Exploratory, Double Blind, Randomized, Placebo-controlled, Parallel Group, Multicenter Study, for the Assessment of Efficacy, Safety and Tolerability of Ucb 34714 50 mg Oral Capsules in b.i.d. Administration at the Doses of 200 mg/Day and 400 mg/Day, in Subjects (at Least 18 Years Old) Suffering From Post Herpetic Neuralgia (PHN)

Conditions
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Neuralgia, Postherpetic

Intervention / Treatment
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* Drug: Placebo
* Drug: Brivaracetam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria: Male/female subject aged 18 years or older. Pain present for at least 6 months after healing of the acute herpes zoster skin rash. Pain intensity score assessed on an 11-point numerical pain rating scale with a score of at least 4 at the screening visit and with an average weekly score of at least 4 on an 11-point numerical pain rating scale during baseline period. Exclusion Criteria: Subject getting any kind of psychological support to help cope with pain such as biofeedback or behavioral cognitive therapy. Subject who had undergone or who is scheduled for neurolytic or neurosurgical therapy for post-herpetic neuralgia (PHN) or who receives trans-electrical neural stimulation (TENS. Tricyclic antidepressants (TCAs) or non-steroidal anti-inflammatory drug (NSAIDs) or permitted opioid analgesics ('strong' opioids are forbidden) that started less than 30 days and/or are not stabilized prior to screening and/or are not expected to be kept stable during the study. Intake of more than two pain treatments at trial entry (screening visit) including Tricyclic antidepressants (TCAs), non-steroidal anti-inflammatory drugs (NSAIDs) or permitted opioid analgesics. Subject being treated with Carbamazepine for any indication. Known coexistent source of painful peripheral neuropathy or other systemic disease associated with a secondary painful neuropathy. Subject being treated in the four weeks prior to screening visit with 'strong' opioid analgesics. Exclusion Criteria:

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching placebo tablets administered twice a day. | Drug: Placebo<br>* Daily oral dose of two equal intakes.<br>|
| Experimental: Brivaracetam 200 mg/day<br>Brivaracetam 200 mg/day (100 mg administered twice a day). | Drug: Brivaracetam<br>* Daily oral dose of two equal intakes.<br>* Other names: Briviact;|
| Experimental: Brivaracetam 400 mg/day<br>Brivaracetam 400 mg/day (200 mg administered twice a day). | Drug: Brivaracetam<br>* Daily oral dose of two equal intakes.<br>* Other names: Briviact;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Average Pain Intensity Score From Baseline to the Last Week of the 4-week Treatment Period | Pain intensity was scored on a 11-point numeric pain rating scale, ranging from 0 to 10 where 0= no pain and 10= worst possible pain. A negative value in percent change from Baseline indicates a decrease in average pain intensity score from Baseline. | Baseline, last week of the 4-week Treatment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate in Average Pain Intensity Score at the Last Week of the Treatment Period Compared to the Baseline Period | A responder is defined as a subject with a >= 30 % reduction in average pain intensity score at the Evaluation Week (last week of the Treatment Period) compared to the Baseline Period. | Baseline, last week of the 4-week Treatment Period | 
| Percent Change From the Baseline Period to Each Weekly Mean in the Pain Intensity Score | Pain intensity was scored on a 11-point numeric pain rating scale, ranging from 0 to 10 where 0= no pain and 10= worst possible pain. A negative value in percent change from Baseline indicates a decrease in average pain intensity score from Baseline. | Baseline, each Evaluation visit (up to Week 4) | 
| Percent Change From the Baseline Period to the Last Week of the Treatment Period in the Sleep Interference Score | Sleep interference was scored on a 11-point numerical sleep interference rating scale, ranging from 0 to 10 where 0 = 'pain does not interfere with sleep', 10 = 'pain completely interferes with sleep'. A negative value in percent change from Baseline indicates a decrease in average sleep interference score from Baseline. | Baseline, last assessment during the 4-week Treatment Period | 
| Percent Change From the Baseline Period to Each Weekly Mean of the Treatment Period in the Sleep Interference Score | Sleep interference was scored on a 11-point numerical sleep interference rating scale, ranging from 0 to 10 where 0 = 'pain does not interfere with sleep', 10 = 'pain completely interferes with sleep'. A negative value in percent change from Baseline indicates a decrease in average sleep interference score from Baseline. | Baseline, each Evaluation visit (up to Week 4) | 
| Absolute Change From the Randomization Visit to the Evaluation / Early Discontinuation Visit in the Total Pain Score of the Short-Form McGill Pain Questionnaire (SF-MPQ) | The SF-MPQ has three components: the first one consists of 15 subscales (descriptors: 11 sensory, 4 affective) which are rated on an intensity scale with 0 = none, 1 = mild, 2 = moderate or 3 = severe. Three pain scores are derived from the sum of the intensity rank values of the words chosen for sensory, affective and total subscales (descriptors). The SF-MPQ also includes a Present Pain Intensity (PPI) index and a visual analogue scale (VAS). Each of the 15 subscales is rated from 0=none to 3=severe pain. The Total Pain Score of the SF-MPQ is the sum of all 15 ratings and can hence vary from 0 (15*0=0: no pain) to 60 (15*4=60: severe pain). The mean change in total score is reported. | Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4) | 
| Absolute Change From the Randomization Visit to the Evaluation / Early Discontinuation Visit in the Sensory Score of the Short-Form McGill Pain Questionnaire (SF-MPQ) | The main component of the SF-MPQ consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. The sensory score ranges from 0 to 33. Change = observation mean at Evaluation / Early Discontinuation visit minus Randomization mean. A negative value in absolute change indicates an improvement. | Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4) | 
| Absolute Change From the Randomization Visit to the Evaluation / Early Discontinuation Visit in the Affective Score of the Short-Form McGill Pain Questionnaire (SF-MPQ) | The main component of the SF-MPQ consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. The affective score ranges from 0 to 12. Change = observation mean at Evaluation / Early Discontinuation visit minus Randomization mean. A negative value in absolute change indicates an improvement. | Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4) | 
| Absolute Change From the Randomization Visit to the Evaluation / Early Discontinuation Visit in the Present Pain Intensity (PPI) Score of the SF-MPQ | Present pain intensity (PPI) was rated by the subject. The score ranges from 0 (no pain) to 5 (excruciating). A negative value in absolute change indicates an improvement in PPI. | Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4) | 
| Absolute Change From the Randomization Visit to the Evaluation / Early Discontinuation Visit in the Visual Analog Scale (VAS) of the SF-MPQ | Pain burden was rated by the subject using the visual analog scale (VAS) ranging from 0 (no pain) to 100 (worst possible pain). A negative value in absolute change indicates an improvement in pain burden. | Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4) | 
| Percentage of Subjects With Categorized Change in Pain Assessed by Patient's Global Evaluation Scale at the Evaluation / Early Discontinuation Visit | Patient´s global assessment of change in pain was performed using a seven-point scale (7= Marked improvement, 6= Moderate improvement, 5= Slight improvement, 4= No change, 3= Slight worsening, 2= Moderate worsening, 1= Marked worsening). | Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4) | 
| Percentage of Subjects With Categorized Change in Post-herpetic Neuralgia Assessed by Investigator's Global Evaluation Scale at the Evaluation / Early Discontinuation Visit | Investigator´s global assessment of change was performed using a seven-point scale (7= Marked improvement, 6= Moderate improvement, 5= Slight improvement, 4= No change, 3= Slight worsening, 2= Moderate worsening, 1= Marked worsening). | Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4) | 
| Percent Change From Randomization Visit to the Evaluation / Early Discontinuation in the Brush-evoked Allodynia Intensity Rated by the Patient | Brush-evoked allodynia intensity was assessed by the subject on an 11-point numerical rating scale, ranging from 0= no pain to 10= unbearable Pain. A negative value in percent change indicates an improvement in brush-evoked allodynia intensity. | Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4) | 
| Percent Change From Randomization Visit to the Evaluation / Early Discontinuation in the Brush-evoked Allodynia Area Measured by the Investigator | Allodynia is pain due to a normally non-painful stimulus. The brush-evoked allodynia areas were assessed by the Investigator (location and contour of the allodynic regions drawn on a standard dermatomal map). Areas (mm²) of the allodynic regions drawn by the Investigator were afterwards computed by means of appropriate tools and calibrated templates. The larger the area in square centimeters the more allodynia. A negative value in percent change in the brush-evoked allodynia area indicates improvement. | Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4) | 

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