Refractory partial-onset seizures with or without secondary generalization MedDRA version: 14.0 Level: PT Classification code 10056209 Term: Partial seizures with secondary generalisation System Organ Class: 10029205 - Nervous system disorders MedDRA version: 14.0 Level: LLT Classification code 10034090 Term: Partial seizures, complex System Organ Class: 10029205 - Nervous system disorders MedDRA version: 14.0 Level: PT Classification code 10040703 Term: Simple partial seizures System Organ C
Conditions
Sponsors
Upsher-Smith Laboratories, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Subject has a confirmed diagnosis of partial-onset seizures with or without secondary generalization for at least 12 months prior to Visit 1. The diagnosis of partial-onset seizures with or without secondary generalized seizure is defined by the ILAE commission in 1981. •Currently on a stable dosing regimen of 1 to 3 AEDs for at least 4-weeks prior to Visit 1 (12 weeks for phenobarbital and primidone). oNote: VNS can be counted as one of the AEDs provided the VNS has been in place for at least 6 months and on a stable setting for at least 1 month prior to Visit 1. The VNS settings must not change throughout the course of the study (baseline, titration, and maintenance phases). oNote: Benzodiazepines (BZD) taken more than once per week, for any indication, will be counted as one of the AEDs. •Male or female, aged 18 to 75 years, inclusive. •Can safely be treated, in the opinion of the investigator, with topiramate •Have a minimum of 8 partial-onset seizures and no more than 21 consecutive seizure free days, during the 8-week baseline. oNote: Only simple partial seizures with motor signs, complex partial seizures, and partial seizures with secondary generalization are counted toward this inclusion. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 284 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: •Have a predisposing condition or medications that may interfere with the absorption of USL255. For example, Crohn’s disease, ileostomy, short bowel syndrome, chronic diarrhea. •Have a history of seizure episodes 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, within 3 months prior to Visit 1. •Have a history of pseudoseizures, or status epilepticus, within 3 months prior to Visit 1. •Have a history of metabolic acidosis, nephrolithiasis, ureterolithiasis, or narrow angle glaucoma. •Have a history of suicidal attempts, suicidal ideation, or uncontrolled psychiatric illness within 2 years of Visit 1. •Have taken topiramate within the past 6 months. •History of lack of efficacy to topiramate, for epilepsy, despite adequate exposure (200mg/day) •History of safety or tolerability issues to topiramate not related to dosage titration •Currently taking, or have taken felbamate within the past 18 months, or have taken vigabatrin in the past.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of USL255 compared to placebo in subjects with refractory partial-onset seizures with or without secondary generalization.;Secondary Objective: To assess the safety of USL255 compared to placebo in subjects with refractory partial-onset seizures with or without secondary generalization.;Primary end point(s): Primary efficacy end point: •Percent reduction from baseline in weekly (7 day) partial-onset seizure frequency during the titration plus maintenance phase. ;Timepoint(s) of evaluation of this end point: Seizure Diary Data will be used for analysis of the primary study endpoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoint •Proportion of subjects with =50% reduction (responder rate) in weekly (7 day) partial-onset seizure frequency during the titration plus maintenance phase compared to baseline. (This could become a primary endpoint to meet country specific regulatory requirements for approval outside the United States.) Other Secondary Efficacy Endpoints •Proportions of subjects with =50% reduction (responder rate) in weekly (7 day) partial-onset seizure frequency during the titration and maintenance phases, separately. •Percent reductions from baseline in weekly (7 day) partial-onset seizure frequency during the titration and maintenance phases, separately. •Percent reduction from baseline in weekly (7 day) all seizure frequency during the titration plus maintenance phase. •Proportions of subjects with =25%, =75%, and 100% reduction in weekly (7 day) partial-onset seizure frequency during the titration, maintenance and titration plus maintenance phases, separately.;Timepoint(s) of evaluation of this end point: Please see E.5.2 | — |
Countries
Argentina, Australia, Belgium, Canada, Chile, Germany, Greece, Hungary, India, Israel, New Zealand, Poland, Russian Federation, South Africa, Spain, United States
Contacts
Public ContactClinical Development
Upsher-Smith Laboratories, Inc.
Outcome results
None listed