| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Partial seizures with or without secondary generalization | |
| MedDRA Classification |
| 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 the trial is to evaluate the efficacy of SPM 927 administered concomitantly with 1, 2, or 3 AEDs in subjects with or without additional VNS who currently have uncontrolled partial seizures with or without secondary generalization. | |
| E.2.2 | Secondary objectives of the trial | | The secondary objectives are to evaluate the safety of SPM 927, the dose-response relationship of SPM 927 with regards to efficacy and safety, and to examine steady-state plasma concentrations of SPM 927 and concomitant AEDs during oral administration of SPM 927. | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | Subjects must fulfill the following inclusion criteria:
1. Subject is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent.
2. Subject is willing and able to comply with all trial requirements.
3. Subject is male or female between 16 and 70 years of age.
4. Subject has a diagnosis of epilepsy with simple partial seizures and/or complex-partial seizures with or without secondary generalization according to the International Classification of Epileptic Seizures (1981).
a) The results of at least one prior electroencephalogram (EEG) and one MRI or CT scan completed within the last 10 years should be consistent with diagnosis of partial seizures due to epilepsy.
5. Subject must have been observed to have partial onset seizures for at least the last two years despite prior therapy with at least 2 AEDs (concurrently or sequentially) and must have been observed to have on the average at least 4 partial onset seizures per 28 days with seizure-free phase no longer than 21 days in the 8-week period prior to entry into the Baseline Phase.
a) In the case of simple partial seizures only those with motor signs will be counted towards meeting the inclusion criterion.
6. Subject must be on a stable dosage regimen of at least 1 but no more than 3 AEDs, with or without additional concurrent stable VNS. The VNS must have been in place for at least 6 months prior to study entry. The dosage of concomitant AED therapy and the settings of VNS must be kept constant for a period of at least 4 weeks prior to entry into the Baseline Phase
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| E.4 | Principal exclusion criteria | Subjects are not permitted to enroll in the trial if any of the following criteria are met:
1. Subject has received SPM 927 in a previous trial.
2. Subject is currently participating or has participated within the last two months in any trial of an investigational drug or experimental device.
3. Subject has a history of chronic alcohol or drug abuse within the previous 2 years.
4. Subject has any medical or psychiatric condition, which in the opinion of the Investigator, could jeopardize the subject’s health or would compromise the subject’s ability to participate in this trial.
5. Subject has a known hypersensitivity to any components of the investigational product(s) as stated in the protocol.
6. Pregnant or nursing women and/or those of childbearing potential who are not surgically sterile, two years postmenopausal or do not practice two combined methods of contraception, unless sexually abstinent, during the duration of the trial.
7. Subject has ALT, AST, alkaline phosphatase, or total bilirubin level greater than or equal to 2 times the upper limit of normal (ULN).
8. Subject has impaired renal function, ie, creatinine clearance (Ccr) is lower than 50mL/min, at Visit 1. Creatinine clearance will be estimated as follows:
Adult males: Ccr = (140-age) x weight in kg/(72 x serum creatinine in mg/dL)
Adult females: Ccr = [(140-age) x weight in kg/(72 x serum creatinine in mg/dL)] x 0.85.
9. Subject with a diastolic blood pressure less than 50mm Hg or greater than 105mm Hg or pulse less than 50bpm or greater than 110bpm, after 3 minutes in a sitting position.
10. Subject has confirmed clinically significant abnormality in electrocardiogram (ECG), including prolonged QTc (Bazett’s, machine-read) interval defined as ≥450ms for males and ≥470ms for females.
11. Subject with a known history of severe anaphylactic reaction or serious blood dyscrasias.
12. Subject with nonepileptic events, including psychogenic seizures, that could be confused with seizures.
13. Subject with seizures that are uncountable due to clustering (i.e., an episode lasting less than 30 minutes in which several seizures occur with such frequency that the initiation and completion of each individual seizure cannot be distinguished) during the 8-week period prior to trial entry.
14. Subject with a history of primary generalized seizures.
15. Subject with a history of status epilepticus within the 12-month period prior to trial entry.
16. Subject with concomitant treatment of felbamate or previous felbamate therapy within the last 6 months prior to trial entry.
17. Subject has taken vigabatrin in the preceding six months. (Note: A subject with a history of vigabatrin treatment must have had a visual perimetry test at least six months following conclusion of treatment. The results of the visual perimetry test must have shown either a normal result or no change from a visual field abnormality that was documented prior to the first administration of vigabatrin.)
18. Subject with a progressive structural lesion in the CNS or a progressive encephalopathy.
19. Subject has any other clinically significant disease, surgical condition or recent chronic consumption of non-AED medications (within the preceding four weeks prior to trial entry), that might reasonably be expected to interfere with drug absorption, distribution, metabolism or excretion.
20. Subject taking one of the following medications influencing the central nervous system on a regular basis within four weeks prior to trial entry: neuroleptics, MAO inhibitors, barbiturates (except for medication taken as concomitant anticonvulsant treatment), and narcotic analgesics.
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| E.5 End points |
| E.5.1 | Primary end point(s) | | Proportion of responders where a responder is a subject experiencing a 50% or greater reduction in partial seizure frequency from baseline to the maintenance phase. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 | The end of the trial is defined as the date of the last visit of the
last patient undergoing the trial.
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| 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 | 6 |
| 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 | 6 |
