| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 | 10061334 |
| E.1.2 | Term | Partial seizures |
|
| 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 |
| To determine the efficacy of BGG492 vs. Placebo in reducing the seizure rate when administered orally for up to 7 days as monotherapy in patients with refractory partial seizures who are undergoing an inpatient pre-surgical diagnostic evaluation for epilepsy surgery. |
|
| E.2.2 | Secondary objectives of the trial |
To determine the efficacy of BGG492 vs. Placebo in reducing the seizure rate when administered orally for up to 9 daysin patients with refractory partial seizures who are undergoing an inpatient pre-surgical diagnostic evaluation for epilepsy surgery.
To determine the efficacy of BGG492 vs. Placebo in reducing the seizure rate when administered orally for up to 2 days in patients with refractory partial seizures who are undergoing an inpatient pre-surgical diagnostic evaluation for epilepsy surgery.
To evaluate the safety and tolerability of BGG492 repeated dose over 9 days in patients with refractory partial seizures and
To determine the plasma levels of BGG492 in patients with refractory partial seizures.
To determine if BGG492 changes the seizure type patterns and/or seizure duration as measured by the seizure types observed and the total seizure duration per day
To evaluate cognitive effects of NVP-BGG492
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female subjects aged 18 to 65 years
2. A diagnosis of partial seizures (with or without secondary generalization) and undergoing an evaluation for epilepsy surgery, based on the classification of the International League Against Epilepsy (ILAE), as modified in 1981.
3. A stable dosing regimen with no more than two (except of association of Lamotrigine with Valproate) antiepileptic drugs (AED) prior to randomization. (Note: allowed AEDs at baseline are: Valproate, Lacosamide, Lamotrigine, Levetiracetam, Carbamazepine, Oxcarbazepine, Phenytoin, Clobazam, Topiramate, Pregabalin, Gabapentin)
4. Willing to be hospitalized for a pre-surgical evaluation and study procedures for up to 10 days.
5. Absence of evolving space-occupying lesions or progressive neurological diseases.
6. Capable of communicating well with the Investigator, understanding and complying with the requirements of the study, satisfying the requirements of the protocol and having understood and signed the written informed consent prior to initiation of any study procedure after the nature of the study has been fully explained.
7. At Screening, and Baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three (3) minutes, and again when required after three (3) minutes in the standing position.
8. Female subjects of childbearing potential must have an established use of oral, injected or implanted hormonal methods of contraception or use two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the entire duration of the study.
Periodic abstinence and withdrawal are not acceptable methods of contraception.
Proof that a discussion has taken place with the Investigator / Nurse has to be
captured as source document.
9. Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to screening. Menopause should be confirmed objectively (such as by serum FSH level of ≥ 40 IU/L). OR: Female subjects who report surgical sterilization must have had the procedure at least six (6) months prior to the initial dosing. Surgical sterilization and hysterectomy procedures must be supported with clinical documentation made available to Sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF.
10. All female subjects must have negative pregnancy test results at screening and baseline.
11. Male subjects must be using a double-method local contraception, (e.g. spermicidal gel plus condom) for the entire duration of the study.
12. Subjects must weigh at least 50 kg to participate in this study and must have a body mass index (BMI) within the range of 18 to 35. |
|
| E.4 | Principal exclusion criteria |
1. Pregnant or nursing females.
2. A diagnosis of generalized seizures (with the exception of secondarily generalized seizures), based on the classification of the International League Against Epilepsy (ILAE), as modified in 1981.
3. A history of frequent and/or severe status epilepticus (i.e. requiring intensive care unit treatment).
4. Current treatment with phenobarbital, primidone or zonisamide
5. Having discontinued chronic benzodiazepine and barbiturate therapy within 30 days prior to the baseline.
6. Having electrodes implanted in the brain.
7. Experiencing pseudo-seizures that may impact the interpretation of seizures observed during the study.
8. Having evidence on physical examination, or a history of any medically significant thyroid, cardiac, respiratory, hepatic, gastrointestinal, renal, hematologic, oncologic, psychiatric or progressive neurological disorder, requiring current medical intervention/therapy likely to have a significant impact on the outcome of this study.
9. Malignancy, or a history of malignancy, within the past five (5) years.
10. With a history of clinically significant drug allergy or a known hypersensitivity to drugs of the same class to the study drug.
11. With any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs, e.g. GI surgery and/or pancreatic or liver disease
12. Having one or more clinically relevant abnormal biochemical or haematological variables or having liver function tests exceeding three times the upper limit of normal values.
13. With evidence or history of drug or alcohol abuse in the three (3) months preceding Screening, or evidence of such abuse as indicated by the laboratory assays conducted during Screening or Baseline.
14. With mental impairment limiting the ability to comply with study requirements.
15. Patient under treatment of Lamotrigine in combination with Valproate
16. Patients using (or having used within four (4) weeks before initial dosing) concomitant medications that are potent inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir, etc.) and Pgp (P-glycoprotein) (e.g. verapamil). See Appendix 2 for a list of medications that are not allowed during the study.
17. Patients using (or having used within four (4) weeks before initial dosing) concomitant medications that are potent inducers of CYP3A4 and Pgp (P-glycoprotein) (e.g. Rifampin St John’s wort), except carbamazepine, oxcarbamazepine and phenytoin. See Appendix 2 for a list of medications that are not allowed during the study.
18. Having participated in any clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations.
19. Having donated or lost 400 mL or more of blood and/or blood components within eight (8) weeks prior to initial dosing, or longer if required by local regulation.
20. Having a significant illness other than epilepsy within two (2) weeks prior to initial dosing.
21. Having a medical history of clinically significant ECG abnormalities or a family history (grandparents, parents and siblings) of a prolonged QT-interval syndrome (as far as is known).
22. Having recent (within the last three (3) years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc).
23. Having a history of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
24. With a positive Hepatitis B surface antigen (HBsAg) test result.
25. Having a medical history of clinically significant episodes of blurry vision and or other visual disturbances that may impact the interpretation of visual disturbances during the trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Pharmacodynamic assessments
• Seizure record: Screening, Baseline, Days 1 to 9/exit
• Continuous EEG Monitoring: Baseline, Days 1 to 9/exit
|
|
| 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 | No |
| 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 | Yes |
| 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.8.3 |
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 | 4 |
| 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 | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
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