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Evaluate the Efficacy of BGG492 as Adjunctive Treatment in Patients With Refractory Partial Onset Seizures

Phase 2
Registration Number
CTRI/2010/091/001332
Lead Sponsor
ovartis Health care Private Limited
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Other (Terminated)
Sex
Not specified
Target Recruitment
57
Inclusion Criteria

Male and female outpatients age 18 to 65 years (inclusive)

2. Weight of greater than or equal to 50 kg (110 lb)

3. Have a diagnosis of epilepsy (more than 2 years before screening) with partial seizures

with or without secondarily generalized seizures according to the International League

Against Epilepsys Classification of Epileptic Seizures (ILAE, 1981) Appendix 5

The Diagnosis should have been established by clinical history and electroencephalogram

(EEG) that is consistent with localization related epilepsy

4. Must have at least 4 partial seizures (defined as simple partial seizures with motor signs,

complex partial seizures, complex partial seizures with secondary generalization or a

combination of these types) during the 4 week baseline period and the 4 weeks

immediately preceding the baseline period

5. Have no 28day seizurefree period during the 8 weeks preceding randomization

6. Must have a positive test result for iGluR3 antibodies in the blood at screening. The mean

plus three standard deviations derived from healthy donors will be chosen as cutoff value.

7. Must have uncontrolled partial seizures despite having been treated with at least two

different antiepileptic drugs within the last 2 years prior to screening (given concurrently

or sequentially)

8. Must be receiving stable treatment (see inclusion criteria 8.1 to 8.4 and 9) with 1 or a

maximum of 2 AEDs from the list presented below:

8.1 No change in medication type, dose or frequency for 8 weeks prior to

randomization: Carbamazepine, Eslicarbazepine, Oxcarbazepine, Phenytoin,

Valproate, Lacosamide, Lamotrigine, Levetiracetam, Clobazam, Topiramate,

Zonisamide, Gabapentin and Pregabalin. Felbamate is only allowed, if treatment

has been continous for greater than or equal to 2 years.

8.2 No change in medication type, dose or frequency for 12 weeks prior to

randomization Phenobarbital and Primidone

8.3 Vagal nerve stimulation (VNS) will be counted as 1 AED. If using a vagal nerve

stimulator, the device must have been implanted for at least 5 months prior to

randomization. Stimulator parameters may not have been changed within 8 weeks

prior to randomization

8.4 Stable benzodiazepine treatment (no change in medication type, dose, or frequency

for 12 weeks prior to randomization) administered for e.g. epilepsy, anxiety, or

sleep disorders will be counted as one AED

Note: The use of intermittent benzodiazepines is defined in the exclusion criteria

2.5, refer to Section 4.2.

9. Must have had either a computed tomography (CT) or magnetic resonance imaging (MRI)

within the 5 years prior to screening that ruled out progressive neurological changes (e.g.

Alzheimerâ??s disease, Parkinsonâ??s disease) in addition, no physical examination changes

suggestive of such lesions or diseases should have occurred since the imaging procedure

If a patient has not had a CT or MRI within the past 5 years, then a MRI must be

performed during the screening period and the results must be reviewed for compliance

with above criterion prior to randomization

10. Patients having had pre-surgical evaluations may be included. Also, patients having had

brain surgery for partial seizures may be included, if surger

Exclusion Criteria

* Presence of only non-motor simple partial seizures
* History of psychogenic seizures
* Absences, myoclonic seizures e.g. in the context of primary generalized epilepsy;
* Previous history of Lennox-Gastaut syndrome
*Pregnant or nursing (lactating) women
* Status epilepticus or seizure clusters, according to the judgement of the investigator, occurring within 52 weeks prior to randomization

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Seizure counts, documenting the percent change in seizure frequency of BGG492 in the maintenance period.Timepoint: 28 days
Secondary Outcome Measures
NameTimeMethod
Pharmacokinetic profile of BGG492 including plasma concentrations of BGG492 at each dose level and derived variables including AUC (area under the curve), Cmax (maximum plasma concentration), Tmax (time to maximum concentration), T1/2 (half life.)Timepoint: 10 weeks;Responder rate: analysis of patients with a 50% or greater reduction in seizure frequency of BGG492 during the maintenance period.Timepoint: 28 days;Safety and tolerability of BGG492 compared to placebo evaluated by continuous adverse event monitoring and assessment of vital signs and ECGs at each visit and laboratory assessments every 2 to 4 weeksTimepoint: 12 weeks
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