Post Herpetic Neuralgia
Conditions
Keywords
post herpetic neuralgia
Brief summary
The primary objective of this study is to assess the efficacy of Eslicarbazepine acetate (ESL) as therapy in subjects with Post-herpetic Neuralgia (PHN) over a 15 week treatment phase.
Detailed description
Post-herpetic neuralgia (PHN) is a syndrome of intractable pain following an acute infection of herpes zoster (shingles). Treatment for PHN is often suboptimal. More than 50% of the subjects fail to respond to pharmacological treatments or experience intolerable side effects. The clinical development of ESL to treat neuropathic pain is based on its chemical and pharmacodynamic relationship to sodium channel blockers, including carbamazepine, which is effective for treating some neuropathic pain conditions. Preclinical data supports the theoretical background. This study will examine the efficacy, safety, tolerability and pharmacokinetics of Eslicarbazepine acetate for the treatment of post herpetic neuralgia.
Interventions
Tablets will be used.
DRUGPlacebo
Tablets will be used.
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female outpatients aged 18 years or older. Female subjects are of nonchildbearing potential, defined as surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or at least 2 years postmenopausal (spontaneous amenorrhea for at least 24 months before Visit 1), or if of childbearing potential, subjects agree to use a medically acceptable nonhormonal method of contraception. * Experiencing pain for at least 6 months after the healing of a herpes zoster skin rash. * A mean score between 4.0 and 9.0, inclusive, on the 24 hour average pain intensity assessment. * Compliance with patient diary completion. * If not used to treat PHN, subjects are permitted to take nonsteroidal anti inflammatory drugs and selective serotonin reuptake inhibitors if they were kept on a stable dose for 1 month prior to Screening and are foreseen to remain stable throughout the study. * Competent and able to freely give own informed consent. * Female subjects of childbearing potential, who are not currently breastfeeding, must have a negative serum pregnancy test at Visit 1.
Exclusion criteria
* Historical exposure to drugs known to cause neuropathy * Significant skin lesions (active infection, ulcer, etc). * Known intolerance to ESL or to other carboxamide derivatives (eg, carbamazepine or oxcarbazepine) or frequent or severe allergic reactions with multiple medications. * Subjects who previously participated in a clinical study with ESL. * Major psychiatric disorder. * Serious or unstable cardiovascular disease that could compromise participation or cause hospitalization during the study. * Second or third degree atrioventricular blockade not corrected with a pacemaker or any clinically significant abnormality in the 12 lead electrocardiogram as determined by the investigator. * Subjects taking the following drug classes and individual drugs are excluded: benzodiazepines (except short half life sleep agents), skeletal muscle relaxants, orally administered steroids, capsaicin, mexiletine, centrally acting analgesics (dextromethorphan, tramadol), opiates, topical lidocaine, anticonvulsants, tricyclic antidepressants, and serotonin norepinephrine reuptake inhibitors. These drugs require a minimum washout period of at least 5 times the half life and should be tapered appropriately using product label instructions as a guide. * Relevant clinical laboratory abnormality that, in the investigator's opinion, can compromise the subject's safety. * History of drug abuse or dependence (drug categories defined by DSM IV) within the past year, excluding nicotine and caffeine. * Subjects who, in the previous 30 days, received treatment with a drug that had not received regulatory approval for any indication at the time of study entry. * History of recurrent epileptic seizures except febrile seizures. * History of severe gastroparesis or gastric bypass surgery. * Neurolytic or neurosurgical treatment for PHN. * Injected anesthetics or steroid use within 30 days of Visit 1. * Malignancy within past 2 years. * History of chronic hepatitis B or C within the past 3 months or human immunodeficiency virus infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Endpoint in Mean Pain | baseline to endpoint | The efficacy analysis was restricted to the primary efficacy variable in the analysis population. The intended treatment period, starting on the day of the randomization and ending at the efficacy cut-off date (October 31, 2011), was the basis for the analysis. The primary efficacy variable was the difference between the mean values of 7 daily pain scores preceding the efficacy cut-off date (endpoint mean pain score), and before randomization (baseline mean pain score), respectively. The daily pain scores were based on the morning response to the 11-point Numeric Rating Pain Scale (NRPS) question relating to average pain intensity over the last 24 hours. The NPRS is an 11-point scale from 0-10 \[0 = no pain; 10 = the most intense pain imaginable\] |
Countries
Germany
Participant flow
Recruitment details
Eighty nine (89) clinical sites in 12 countries Study period: Date of first admission: 2010.09.28 Date of last visit: 2012.04.23
Participants by arm
| Arm | Count |
|---|---|
| Esl 1600 mg QD Eslicarbazepine acetate (Esl) (BIA 2-093): Tablets will be used. | 60 |
| Esl 1200 mg QD Eslicarbazepine acetate (Esl) (BIA 2-093): Tablets will be used. | 60 |
| Esl 800 mg Once Daily (QD) Eslicarbazepine acetate (Esl) (BIA 2-093): Tablets will be used. | 60 |
| Placebo Placebo: Tablets will be used. | 60 |
| Total | 240 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 24 | 15 | 15 | 7 |
| Overall Study | Lack of Efficacy | 2 | 3 | 1 | 3 |
| Overall Study | Physician Decision | 2 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 3 | 2 | 3 |
Baseline characteristics
| Characteristic | Esl 1600 mg QD | Esl 1200 mg QD | Esl 800 mg Once Daily (QD) | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 16.71 | 65.4 years STANDARD_DEVIATION 14.47 | 65.9 years STANDARD_DEVIATION 15.6 | 65.4 years STANDARD_DEVIATION 14.43 | 64.9 years STANDARD_DEVIATION 15.27 |
| Sex: Female, Male Female | 24 Participants | 23 Participants | 35 Participants | 25 Participants | 107 Participants |
| Sex: Female, Male Male | 36 Participants | 37 Participants | 25 Participants | 35 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 46 / 60 | 45 / 60 | 40 / 60 | 6 / 60 |
| serious Total, serious adverse events | 2 / 60 | 6 / 60 | 4 / 60 | 2 / 60 |
Outcome results
Primary
Change From Baseline to Endpoint in Mean Pain
The efficacy analysis was restricted to the primary efficacy variable in the analysis population. The intended treatment period, starting on the day of the randomization and ending at the efficacy cut-off date (October 31, 2011), was the basis for the analysis. The primary efficacy variable was the difference between the mean values of 7 daily pain scores preceding the efficacy cut-off date (endpoint mean pain score), and before randomization (baseline mean pain score), respectively. The daily pain scores were based on the morning response to the 11-point Numeric Rating Pain Scale (NRPS) question relating to average pain intensity over the last 24 hours. The NPRS is an 11-point scale from 0-10 \[0 = no pain; 10 = the most intense pain imaginable\]
Time frame: baseline to endpoint
Population: efficacy population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Esl 1600 mg QD | Change From Baseline to Endpoint in Mean Pain | -1.19 units on a scale | Standard Error 0.29 |
| Esl 1200 mg QD | Change From Baseline to Endpoint in Mean Pain | -1.34 units on a scale | Standard Error 0.277 |
| Esl 800 mg Once Daily (QD) | Change From Baseline to Endpoint in Mean Pain | -0.94 units on a scale | Standard Error 0.281 |
| Placebo | Change From Baseline to Endpoint in Mean Pain | -0.77 units on a scale | Standard Error 0.293 |
p-value: 0.9321Dunnett's test
p-value: 0.261Dunnett's test
p-value: 0.4764Dunnett's test