| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Post-herpetic neuralgia (PHN). |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10036376 |
| E.1.2 | Term | Post herpetic neuralgia |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to assess the efficacy of ESL as therapy in subjects with PHN over a 15 week treatment phase. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective of this study is to assess the safety, tolerability, and pharmacokinetics of ESL in subjects with PHN over a 19 week treatment phase. It is also to evaluate the safety and tolerability of ESL at doses titrated to an efficacy or safety endpoint over a 36 week OL phase and the maintenance of therapeutic effect of ESL over 32 weeks of OL ESL at flexible doses. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. 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 (Section 3.8.7).
2. Experiencing pain for at least 6 months after the healing of a herpes zoster skin rash. Subjects with PHN involving the trigeminal nerve must have medical documentation of a history of herpes zoster lesions, to avoid enrolling subjects with trigeminal neuralgia of mechanical etiology.
3. A mean score between 4.0 and 9.0, inclusive, on the 24 hour average pain intensity assessment; the mean is determined by averaging all available daily scores from the 24 hour average pain assessment in the subject eDiary from the last 7 days before Visit 3. The period between Visit 2 and Visit 3 can vary between 7 to 10 days. To be randomly assigned, a subject must have at least 5 assessments of 24 hour average pain from the last 7 days prior to randomization.
4. A subject rated score at Visit 3 of 40 mm or more on a 100 mm VAS for post herpetic pain during the previous 24 hours.
5. Daily eDiaries must be completed for at least 70% of the 7 to 10 days between Visit 2 and Visit 3 (ie, 5 of 7 days, 6 of 8 days, 7 of 9 days, or 7 of 10 days).
6. 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.
7. Competent and able to freely give own informed consent.
8. A degree of education and understanding sufficient to communicate intelligibly with the investigator and other study center staff.
9. Considered reliable and agree to keep all appointments for protocol required study visits, tests, and procedures.
10. Female subjects of childbearing potential, who are not currently breastfeeding, must have a negative serum pregnancy test at Visit 1. |
|
| E.4 | Principal exclusion criteria |
1.Historical exposure to drugs known to cause neuropathy, such as vincristine, or a history of a medical condition, including pernicious anemia and hypothyroidism, that could have caused neuropathy.
2.Other chronic pain conditions not associated with PHN. However, subjects will not be excluded if all the following criteria apply:
• Pain is located in a different region of the body,
• Pain intensity is not greater than the pain intensity of PHN, and
• Subject can assess PHN pain independently of the other pain condition.
3. Significant skin lesions (active infection, ulcer, etc) that could interfere with pain assessment.
4. Known intolerance to ESL or to other carboxamide derivatives (eg, carbamazepine or oxcarbazepine) or frequent or severe allergic reactions with multiple medications.
5. Subjects who previously participated in a clinical study with ESL.
6. Current or previous (within the past year) axis 1 diagnosis of major depressive disorder, mania, bipolar disorder, psychosis, dysthymia, generalized anxiety disorder, alcohol abuse, history of suicide attempt, or eating disorders according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM
IV) American Psychiatric Association, 2000 criteria, as determined by the investigator.
7. Serious or unstable cardiovascular, hepatic, renal, respiratory, ophthalmologic, gastrointestinal or hematologic illness, symptomatic peripheral vascular disease, or other medical condition that the investigator considers would compromise participation or likely cause hospitalization during the study.
8. Second- or third degree atrioventricular blockade not corrected with a pacemaker or any clinically significant abnormality in the 12 lead ECG as determined by the investigator.
9. 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.
10. Taking excluded medications that cannot be stopped prior to Visit 2.
11. Plasma sodium less than 130 mmol/L, alanine or aspartate aminotransferases greater than 2.0 times above the upper limit of the normal range, white blood cell count less than 3000 cells/mm3, or any other relevant clinical laboratory abnormality that, in the investigator’s opinion, can compromise the subject’s safety.
12. Prior renal transplant or current renal dialysis.
13. History of drug abuse or dependence (drug categories defined by DSM IV) within the past year, excluding nicotine and caffeine.
14. Subjects with a positive Visit 1 drugs of abuse screen test will be excluded from the study, except for medications used to treat a medical condition (including PHN) and reported as such by the subject at Visit 1 (screening visit). These subjects can wash out the medication and be retested at Visit 3. All subjects must have a
negative result at Visit 3.
15. An estimated creatinine clearance of less than 50 mL/min calculated using the 4 variable Modification of Diet in Renal Disease method.
16. Unwilling or unable to comply with the use of an eDiary to directly record subject data.
17. Study center personnel directly affiliated with the study or their immediate families, defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
18. Employees of BIAL or PPD.
19. 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.
20. History of recurrent epileptic seizures except febrile seizures.
21. History of severe gastroparesis or gastric bypass surgery.
22. Neurolytic or neurosurgical treatment for PHN.
23. Injected anesthetics or steroid use within 30 days of Visit 1.
24. Malignancy within past 2 years, except basal cell carcinoma that has been treated.
25. History of chronic hepatitis B or C within the past 3 months or human immunodeficiency virus infection. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable will be the change from Baseline to endpoint in mean pain, defined as the mean of all available pain scores (relating to average pain intensity over the last 24 hours) in the last 7 days of the treatment maintenance phase (while on study drug). Likewise, baseline mean pain will be defined as the mean of all available pain scores in the last 7 days prior to randomization. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| The trial has an open label phase |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 43 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last visit of the last subject undergoing the trial. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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