E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065336 |
E.1.2 | Term | Partial epilepsy |
E.1.2 | System Organ Class | 100000004852 |
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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 YKP3089 at dosages up to 200 mg/day in
reducing seizure frequency when compared to
baseline in subjects with partial onset seizures not
fully controlled despite their treatment with 1 to 3
concomitant AEDs. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety and
tolerability of YKP3089. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female subjects age 18-65 years inclusive.
2) A body mass index (BMI) between 18 and 40 inclusive.
3) Provide written informed consent signed by the subject or legal guardian prior to entering the study in accordance with the ICH, GCP guidelines.
4) Subjects in otherwise good health (with the exception of epilepsy), as determined by the PI via the medical history, a physical examination and screening laboratory investigations.
5) A diagnosis of treatment resistant partial epilepsy by the International League Against
Epilepsy criteria, as defined by: failed treatment, as demonstrated by continued seizures.
6) History of epilepsy for at least 2 years.
7) The subject must have had an EEG consistent with partial epilepsy.
8) Have at least 3 simple partial with motor component, complex partial or secondarily generalized seizures per month with no 21 day seizure free period.
9) Currently treated on a stable dose of :
• 1–3 AED’s for at least 12 weeks prior to randomization (Visit 3).
• VNS will not be counted as AED; however the parameters must remain stable for at least 4 weeks prior to baseline. The VNS must have been implanted >/= 5 months prior to Visit 1
• Benzodiazepines taken at least once per week during the one month prior to Visit 1 for epilepsy, or for anxiety or sleep disorder, will be counted as 1 AED. Therefore
only a maximum of two additional approved AEDs will be allowed. 10) CT or MRI scan performed within the last 5 years. If a CT or MRI has not been performed within the last 5 years, one must be performed prior to randomization. (A neuroimaging examination must have been performed in order to identify a potential cause of epileptic seizures following their initial occurrence)
11) Subject can be reached by telephone. |
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E.4 | Principal exclusion criteria |
1) A history of non-epileptic or psychogenic seizures.
2) Presence of only non-motor simple partial seizures or primary generalized epilepsies.
3) Seizure clusters where individual seizures cannot be counted.
4) Presence or previous history of Lennox Gastaut syndrome.
5) Scheduled or confirmed epilepsy surgery within 6 months after Visit 1.
6) Women who are pregnant or lactating.
7) Women of reproductive potential who do not agree to use effective birth-control methods.
8) Any clinically significant laboratory abnormality which, in the opinion of the investigator, will exclude the subject from the study.
9) Liver transaminases (AST and ALT) cannot exceed twice the upper limit of normal and total and direct bilirubin must be within normal limits.
10) An active CNS infection, demyelinating disease, degenerative neurological disease or any CNS disease deemed to be progressive during the course of the study that may confound
the interpretation of the study results.
11) Any clinically significant psychiatric illness, psychological or behavioral problems which, in the opinion of the investigator, would interfere with the subject’s ability to participate in the study.
12) Suffering from psychotic disorders and/or unstable recurrent affective disorders evident by use of antipsychotics; subject with current major depressive episode (or within 6 months).
13) Use of intermittent rescue benzodiazepines more than once/month (1-2 doses in a 24-hour period is considered one rescue) in the one month period prior to Visit 1.
14) Subjects who at screening have a fall in systolic blood pressure of >20mmHg after standing for 3 minutes.
15) A history of alcoholism, drug abuse, or drug addiction within the past 2 years.
16) Subjects taking felbamate with less than 18 months continuous exposure.
17) Subjects taking phenytoin, phenobarbitone (phenobarbital) or metabolites of these drugs
18) The subject is currently taking vigabatrin or has taken vigabatrin within the past year.
Subjects with a prior history of treatment with vigabatrin will be excluded if they do not have a documented examination of visual fields by an ophthalmologist or neuroophthalmologist, or if the results of these exams are abnormal.
19) Subject has had status epilepticus within 1 year of Visit 1.
20) Subject has had greater than 2 allergic reactions to an AED or one serious hypersensitivity reaction to an AED.
21) Creatinine clearance < 50mL/min
22) A clinically significant ECG abnormality including QTcF <340msec or >450msec.
23) Subjects treated with VPA may have platelet counts no lower than 80,000/μL.
24) Patients with a history of suicide attempt and suicidal ideation
25) Subjects who have participated in any other trials involving an investigational product or device within 30 days of screening or longer as required by local regulations.
26) Subjects taking any of the following medications for 1 week prior to Visit 1: clopidogrel, diazepam, phenytoin, phenobarbitone, omeprazole, fluvoxamine, amitriptylene, clomipramine, buproprion, methadone, ifosfamide, cyclophosphamide, efavirenz, and
natural progesterone. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: Percent change in seizure
frequency per 28 days in the Treatment Period
compared to the Baseline in the Intention to Treat
(ITT) Population. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoint: Responder rate: An
analysis of subjects who experience a 50% or greater
reduction in seizure frequency in the Treatment
Period of the Double-blind Phase. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 |
India |
Korea, Democratic People's Republic of |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |