Postherpetic Neuralgia
Conditions
Keywords
pain herpetic neuralgia
Brief summary
The primary objective of the study is to assess the efficacy of eslicarbazepine acetate (ESL) as therapy for patients with post-herpetic neuralgia.
Interventions
Scored tablets
DRUGPlacebo
oral route
Sponsors
Bial - Portela C S.A.
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
No
Inclusion criteria
* Written informed consent to participate in the study * Men and women aged 18 years or older * Previous diagnosis of herpes zoster * Diagnosis of postherpetic neuralgia and neuropathic pain present for more than 3 months after healing of the herpes zoster skin rash * Cooperation and willingness to complete all aspects of the study * Completion of at least 4 daily diaries during the week preceding randomisation * A minimum average daily pain score of 4 on the NRPS in the last 4 diary entries before randomisation.
Exclusion criteria
* Pain of other origin that might confound the assessment of neuropathic pain of postherpetic origin * Active herpes zoster lesion or dermatitis of any origin at the affected site * Subjects who had neurological ablation by block or neurosurgical intervention for control of pain * Significant or unstable medical or psychiatric disorders * Drug or alcohol abuse in the preceding 2 years * Severe renal function impairment, as shown by calculated creatinine clearance values \< 30 mL/min at screening * Relevant clinical laboratory abnormalities (e.g., Na+ \<130 mmol/L, alanine (ALT) or aspartate (AST) transaminases \>2.0 times the upper limit of the normal, white blood cell count (WBC) \<2,500 cells/mm3) * Previous participation in any study with eslicarbazepine acetate * Pregnancy or breast feeding * History of hypersensitivity to the investigational products or to drugs with a similar chemical structure * History of non-compliance * Likelihood of requiring treatment during the study period with drugs or other interventions not permitted by the clinical study protocol * Participation in a clinical study within 3 months prior to screening * Any clinical significant concomitant condition which might influence the assessments or conduct of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain | baseline and 13 weeks | The primary efficacy variable will be based upon an 11-point (0-10) Numeric Rating Pain Scale (NRPS), where 0 = no pain and 10 = worst possible pain, to be recorded in a patient's diary upon awakening each morning. This score should reflect the patient's mean pain over the previous 24 hours. Please note that the change from baseline to endpoint in mean pain, i.e. the difference between endpoint mean pain and baseline mean pain, which are defined as follows: * Baseline mean pain is defined as the mean of the last four available ratings of average daily pain (NRPS) in the patient diary performed in the last 7 days before randomisation. * Endpoint mean pain is defined as the mean of the last four available ratings of average daily pain in the patient diary in the last 7 days of the treatment period. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Pain (NRPS) From Baseline to Endpoint by Total Daily Dose | baseline and 13 weeks | Details of neuropathic pain, as recorded in a subject diary, were used for the primary assessment of analgesic efficacy. Subjects assessed their pain using an 11-point (0 no pain to 10 worst possible pain) NRPS upon awakening each morning and recorded the results in the subject diary. This score reflected the subject's mean pain over the previous 24 hours. Subjects were trained how to record their pain reliably. Investigators were trained in the subject's NRPS use during site initiation visits and at the investigators' meeting. |
Participant flow
Recruitment details
First subject enrolled 06 November 2007; Date last subject completed: 19 January 2009. Number of subjects: Planned: 540 subjects (90 in each of the 6 treatment groups). Randomised and treated: 567. Analysed for efficacy (per-protocol): 396 Analysed for safety: 567.
Pre-assignment details
An up to 2-week baseline was followed by a 1-week titration period, an 8-week maintenance period, and a 2-week safety follow-up period. If subjects had a creatinine clearance between 30 and 60 mL/min, they received half of the assigned dose, and subjects with a creatinine clearance below 30 mL/min were not enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| ESL 1200 mg Once Daily ESL 1200 mg once daily
Eslicarbazepine acetate : Scored tablets | 102 |
| ESL 400 mg Twice-daily ESL 400 mg twice-daily
Eslicarbazepine acetate : Scored tablets | 94 |
| ESL 600 mg Twice Daily ESL 600 mg twice daily
Eslicarbazepine acetate : Scored tablets | 94 |
| ESL 800 mg Once-daily ESL 800 mg once-daily
Eslicarbazepine acetate : Scored tablets | 94 |
| ESL 800 mg Twice Daily ESL 800 mg twice daily
Eslicarbazepine acetate : Scored tablets | 90 |
| Placebo placebo
Placebo : oral route | 93 |
| Total | 567 |
Baseline characteristics
| Characteristic | ESL 1200 mg Once Daily | ESL 400 mg Twice-daily | ESL 600 mg Twice Daily | ESL 800 mg Once-daily | ESL 800 mg Twice Daily | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized >=65 years | 68 participants | 58 participants | 59 participants | 57 participants | 60 participants | 55 participants | 357 participants |
| Age, Customized Between 18 and 65 years | 34 participants | 36 participants | 35 participants | 37 participants | 30 participants | 38 participants | 210 participants |
| Sex: Female, Male Female | 69 Participants | 55 Participants | 57 Participants | 52 Participants | 64 Participants | 44 Participants | 341 Participants |
| Sex: Female, Male Male | 33 Participants | 39 Participants | 37 Participants | 42 Participants | 26 Participants | 49 Participants | 226 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 48 / 102 | 41 / 94 | 42 / 94 | 46 / 94 | 49 / 90 | 29 / 93 |
| serious Total, serious adverse events | 1 / 102 | 4 / 94 | 4 / 94 | 2 / 94 | 1 / 90 | 0 / 93 |
Outcome results
Primary
Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain
The primary efficacy variable will be based upon an 11-point (0-10) Numeric Rating Pain Scale (NRPS), where 0 = no pain and 10 = worst possible pain, to be recorded in a patient's diary upon awakening each morning. This score should reflect the patient's mean pain over the previous 24 hours. Please note that the change from baseline to endpoint in mean pain, i.e. the difference between endpoint mean pain and baseline mean pain, which are defined as follows: * Baseline mean pain is defined as the mean of the last four available ratings of average daily pain (NRPS) in the patient diary performed in the last 7 days before randomisation. * Endpoint mean pain is defined as the mean of the last four available ratings of average daily pain in the patient diary in the last 7 days of the treatment period.
Time frame: baseline and 13 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ESL 1200 mg Once Daily | Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain | -1.9447 Points | Standard Error 0.2088 |
| ESL 400 mg Twice-daily | Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain | -1.9786 Points | Standard Error 0.2178 |
| ESL 600 mg Twice Daily | Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain | -1.6798 Points | Standard Error 0.2179 |
| ESL 800 mg Once-daily | Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain | -1.6633 Points | Standard Error 0.2217 |
| ESL 800 mg Twice Daily | Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain | -2.0834 Points | Standard Error 0.228 |
| Placebo | Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain | -1.5441 Points | Standard Error 0.2197 |
Other Pre-specified
Change in Mean Pain (NRPS) From Baseline to Endpoint by Total Daily Dose
Details of neuropathic pain, as recorded in a subject diary, were used for the primary assessment of analgesic efficacy. Subjects assessed their pain using an 11-point (0 no pain to 10 worst possible pain) NRPS upon awakening each morning and recorded the results in the subject diary. This score reflected the subject's mean pain over the previous 24 hours. Subjects were trained how to record their pain reliably. Investigators were trained in the subject's NRPS use during site initiation visits and at the investigators' meeting.
Time frame: baseline and 13 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ESL 1200 mg Once Daily | Change in Mean Pain (NRPS) From Baseline to Endpoint by Total Daily Dose | -1.5448 Points | Standard Error 0.2196 |
| ESL 400 mg Twice-daily | Change in Mean Pain (NRPS) From Baseline to Endpoint by Total Daily Dose | -1.8183 Points | Standard Error 0.1512 |
| ESL 600 mg Twice Daily | Change in Mean Pain (NRPS) From Baseline to Endpoint by Total Daily Dose | -2.0854 Points | Standard Error 0.2279 |
| ESL 800 mg Once-daily | Change in Mean Pain (NRPS) From Baseline to Endpoint by Total Daily Dose | -1.8236 Points | Standard Error 0.1565 |