| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of seizures of partial origin in subjects with refractory epilepsy |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10015037 |
| E.1.2 | Term | Epilepsy |
|
| 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 evaluate the efficacy of adjunctive OXC XR (Supernus
Pharmaceuticals, Inc.) in the treatment of seizures of partial origin in subjects with refractory epilepsy
on at least one and up to three other antiepileptic drugs (AEDs) in adults. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
• To assess the safety and tolerability of adjunctive OXC XR in the treatment of seizures of
partial origin in subjects with refractory epilepsy on at least one and up to three other AEDs;
• To assess the effect of OXC XR on the Subject’s Global Impression of Change in his/her
epilepsy status;
• To assess the effect of OXC XR on quality of life as assessed by the Quality of Life in
Epilepsy Inventory-31 (QOLIE-31); and
• To assess secondarily generalized seizures for each treatment group. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Capable of complying with the study procedures.
2) Able to provide written informed consent prior to any study procedure being conducted.
3) Male or female aged 18 to 65 years, inclusive.
4) Current diagnosis of partial onset seizures with or without secondarily generalized seizures as
confirmed by the 1981 and 1989 International League Against Epilepsy [ILAE] Classifications.
5) Experiencing at least three countable partial seizures per 28 days on average during the eightweek
Baseline Phase, or during the four-week Baseline plus the four-week period prior to
Baseline, assuming the recording method is considered acceptable. Simple partial seizures in the
Baseline Phase must have had an observable motor component.
6) Currently receiving treatment with at least one and up to three AEDs with AED therapy remaining
at a stable dose for at least four weeks prior to Baseline (equivalent to 12 weeks prior to
randomization). A vagal nerve stimulator (VNS) will be allowed, but will not be considered as one
of the concomitant AEDs for the purpose of inclusion into the study. The VNS must have been
implanted for at least six months prior to randomization. Stimulator parameters may not be
changed for at least one month prior to screening (equivalent to 12 weeks prior to randomization)
or during the study. Note, magnet use will be allowed, but must be documented throughout the
study.
7) History of being refractory on at least one and up to three AEDs in single or combination use.
8) Magnetic resonance imaging (MRI), with or without contrast, or computerized tomography (CT),
within the past 5 years showing no progressive neurological conditions. For subjects with MRI or
CT older than 5 years, the MRI or CT can be performed in screening.
9) Use of prescription medications, except those specifically prohibited by protocol, and over-thecounter
products, including natural food supplements, vitamins, garlic as a supplement, will be
permitted as long as a stable dose has been maintained for four weeks prior to receiving study
medication (SM).
10) Weight ≥ 41kg.
11) Sexually active women, unless surgically sterile (at least 6 months prior to SM administration) or
at least 1 year post-menopausal, must use an effective method of avoiding pregnancy (including
oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a
secondary method], intrauterine device, female condom with spermicide, diaphragm with
spermicide, cervical cap, abstinence, use of condom with spermicide by sexual partner or sterile
[at least 6 months prior to SM administration] sexual partner) for at least four weeks prior to SM
administration, and must agree to continue using such precautions through the End of Study visit.
Cessation of birth control after this point should be discussed with a responsible physician. |
|
| E.4 | Principal exclusion criteria |
1) History of being refractory to OXC for reasons of efficacy based on 1200mg/day dose and
2-month trial period.
2) A documented history of generalized status epilepticus within the past 2 years.
3) A documented history of non-epileptic seizures in the past 2 years.
4) Seizures secondary to illicit drug or alcohol use, infection, neoplasia, demyelinating disease,
degenerative neurological disease, or central nervous system disease deemed progressive,
metabolic illness, or progressive degenerative disease.
5) Diagnosis or an encephalogram consistent with a diagnosis of seizure disorders other than partial
epilepsy.
6) Meets criteria for current major depressive episode, according to Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition Text Revision, within 6 months prior to
Screening (Visit 1).
7) Current use of antidepressants. However, those subjects who are only taking a stable dose of
either a selective serotonin reuptake inhibitor (SSRI) antidepressant drug or a serotonin and
norepinephrine reuptake inhibitor (SNRI) antidepressant drug for a diagnosed depressive disorder
can be included as long as they have been on the SSRI or SNRI for a period of at least 56 days
prior to randomization. Other antidepressant medications will not be allowed.
8) Active suicidal plan/intent or active suicidal thoughts in the past 6 month.
9) Suicide attempt within the last 2 years;
10) More than one lifetime suicide attempt.
11) History or presence of clinically significant, chronic medical condition, including hyponatremia,
especially those contraindicating antiseizure medication (e.g., any neurological, gastrointestinal,
endocrine, cardiovascular, pulmonary, hematological, immunologic, renal, hepatic, or metabolic
disease) that may affect the safety of the subject in the opinion of the Investigator.
12) Current use of oxcarbazepine.
13) Phenytoin use is allowed if the subject is on a stable dose and the results of two consecutive
serum phenytoin levels are <15 mcg/mL. One of the two levels must be drawn at screening.
14) Use of felbamate with less than 18 months of continuous exposure prior to screening.
15) Frequent need of rescue benzodiazepines (more than once in a 7 day period).
16) Current use of diuretics or other sodium (Na+) lowering non-anti-epileptic medications.
17) History or presence of clinically significant laboratory, electrocardiogram (ECG), or vital sign
(systolic blood pressure [SBP] <90 or >140 millimeters of mercury [mmHg], diastolic blood
pressure [DBP] <40 or >90mmHg, or heart rate [HR] <40 or >100 beats per minute [BPM])
abnormalities at screening that may affect the safety of the subject, in the opinion of the
Investigator.
18) Presence of potential hepatic function impairment as shown by, but not limited to alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) values >3 times upper limit of
normal (ULN), or total bilirubin >1.5 ULN.
19) Presence of suspected impairment of renal function defined by serum creatinine ≥1.5 times ULN.
20) History of alcohol abuse within two years prior to the screening.
21) History of substance abuse or dependence within two years prior to screening.
22) Females who are pregnant or lactating.
23) Previous known hypersensitivity to OXC or other related drugs, such as carbamazepine, or any of
the product components.
24) Use of an investigational drug or device, or participation in an investigational study within 30 days
prior to the first dose of SM.
25) Difficulty swallowing SM tablets.
26) Any reason which, in the opinion of the Investigator, would prevent the subject from participating
in the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The percentage change (PCH) in partial seizure frequency per 28 days during the Treatment Phase
(excluding the 3-week Tapering or Conversion Period) relative to the Baseline Phase in the ITT population. All partial seizures up to the point of subject discontinuation (excluding partial seizures during the 3-week Tapering or Conversion Period) will be included in the analysis.
28-day partial seizure frequency = (# partial seizures during the specified study phase/# days duringthe specified study phase) X 28 |
|
| 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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | No |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
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