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

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)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00160667

Enrollment

152

Registered

2005-09-12

Start date

2004-10-11

Completion date

2006-01-05

Last updated

2019-01-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neuralgia, Postherpetic

Keywords

Post-herpetic Neuralgia (PHN), Brivaracetam

Brief summary

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.

Interventions

DRUGPlacebo

Daily oral dose of two equal intakes.

DRUGBrivaracetam

Daily oral dose of two equal intakes.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage Change in Average Pain Intensity Score From Baseline to the Last Week of the 4-week Treatment Period	Baseline, 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.

Secondary

Measure	Time frame	Description
Percent Change From the Baseline Period to Each Weekly Mean in the Pain Intensity Score	Baseline, each Evaluation visit (up to Week 4)	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.
Percent Change From the Baseline Period to the Last Week of the Treatment Period in the Sleep Interference Score	Baseline, last assessment during the 4-week Treatment Period	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.
Percent Change From the Baseline Period to Each Weekly Mean of the Treatment Period in the Sleep Interference Score	Baseline, each Evaluation visit (up to Week 4)	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.
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)	Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4)	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.
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)	Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4)	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.
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)	Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4)	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.
Responder Rate in Average Pain Intensity Score at the Last Week of the Treatment Period Compared to the Baseline Period	Baseline, last week of the 4-week Treatment 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.
Absolute Change From the Randomization Visit to the Evaluation / Early Discontinuation Visit in the Visual Analog Scale (VAS) of the SF-MPQ	Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4)	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.
Percentage of Subjects With Categorized Change in Pain Assessed by Patient's Global Evaluation Scale at the Evaluation / Early Discontinuation Visit	Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4)	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).
Percentage of Subjects With Categorized Change in Post-herpetic Neuralgia Assessed by Investigator's Global Evaluation Scale at the Evaluation / Early Discontinuation Visit	Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4)	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).
Percent Change From Randomization Visit to the Evaluation / Early Discontinuation in the Brush-evoked Allodynia Intensity Rated by the Patient	Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4)	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.
Percent Change From Randomization Visit to the Evaluation / Early Discontinuation in the Brush-evoked Allodynia Area Measured by the Investigator	Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4)	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.
Absolute Change From the Randomization Visit to the Evaluation / Early Discontinuation Visit in the Present Pain Intensity (PPI) Score of the SF-MPQ	Randomization visit, Evaluation / Early Discontinuation visit (up to Week 4)	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.

Countries

Belgium, Bulgaria, Czechia, France, Germany, Poland, Serbia, Slovakia, Spain, United Kingdom

Participant flow

Recruitment details

The study started to enroll patients in October 2004 and concluded in January 2006.

Pre-assignment details

Participant Flow refers to the Randomized Set.

Participants by arm

Arm	Count
Placebo Matching placebo tablets administered twice a day.	50
Brivaracetam 200 mg/Day Brivaracetam 200 mg/day (100 mg administered twice a day).	51
Brivaracetam 400 mg/Day Brivaracetam 400 mg/day (200 mg administered twice a day).	51
Total Title	152
Total	304

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	3	1	4
Overall Study	Lack of Efficacy	0	1	0
Overall Study	Patient decision	0	0	1
Overall Study	Protocol Violation	0	1	0
Overall Study	Withdrawal by Subject	2	0	1

Baseline characteristics

Characteristic	Placebo	Brivaracetam 200 mg/Day	Brivaracetam 400 mg/Day	Total Title
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	33 Participants	29 Participants	28 Participants	90 Participants
Age, Categorical Between 18 and 65 years	17 Participants	22 Participants	23 Participants	62 Participants
Age, Continuous	66.06 years STANDARD_DEVIATION 10.8	65.33 years STANDARD_DEVIATION 10.95	65.58 years STANDARD_DEVIATION 10.21	65.65 years STANDARD_DEVIATION 10.59
Sex: Female, Male Female	29 Participants	28 Participants	30 Participants	87 Participants
Sex: Female, Male Male	21 Participants	23 Participants	21 Participants	65 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 50	0 / 51	0 / 51
other Total, other adverse events	8 / 50	19 / 51	18 / 51
serious Total, serious adverse events	0 / 50	0 / 51	1 / 51

Outcome results

Primary

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.

Time frame: Baseline, last week of the 4-week Treatment Period

Population: Only subjects with valid data for average pain intensity score at Baseline and the last week of the 4-week Treatment Period are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Percentage Change in Average Pain Intensity Score From Baseline to the Last Week of the 4-week Treatment Period	-26.16 percentage of change	Standard Deviation 30.2
Brivaracetam 200 mg/Day	Percentage Change in Average Pain Intensity Score From Baseline to the Last Week of the 4-week Treatment Period	-26.11 percentage of change	Standard Deviation 33.73
Brivaracetam 400 mg/Day	Percentage Change in Average Pain Intensity Score From Baseline to the Last Week of the 4-week Treatment Period	-27.36 percentage of change	Standard Deviation 34.58

p-value: =0.96595% CI: [-12.82, 13.41]ANCOVA

p-value: =0.82595% CI: [-11.69, 14.65]ANCOVA

Secondary

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.