Safety of Intravenous Lacosamide Dose Followed by Twice Daily Oral Lacosamide in Subjects With Partial-onset Seizures

Study Overview
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Brief Summary
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The purpose of the trial is to evaluate the safety of intravenous (iv) lacosamide delivered in a single dose followed by 6.5 days of oral lacosamide treatment in subjects with partial-onset seizures.

Detailed Description
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This multicenter, open-label trial examined safety and tolerability of rapid initiation of adjunctive lacosamide via a single intravenous loading dose followed by oral maintenance treatment in subjects 16 - 60 years of age with partial-onset seizures. Three consecutive 25-subject cohorts were given a progressively increasing dose of lacosamide (200, 300, 400 mg) administered as a single 15-minute intravenous (iv) loading dose followed by the equivalent daily dose administered orally twice daily for 6.5 days with the first oral dose 12 hours after the iv dose. A fourth cohort of 25 subjects repeated the 300 mg dose to provide safety data on a total of 50 subjects at the highest well-tolerated dose.

Official Title
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A Multicenter, Open-label Trial to Assess the Safety and Tolerability of a Single Intravenous Loading Dose of Lacosamide Followed by Oral Lacosamide Maintenance as Adjunctive Therapy in Subjects With Partial-onset Seizures

Conditions
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Partial Epilepsies, Partial Onset Seizures

Intervention / Treatment
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* Drug: lacosamide
* Drug: lacosamide
* Drug: lacosamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of epilepsy with simple partial seizures and/or complex partial seizures Stable dose regimen of 1 to 2 marketed antiepileptic drug(s) (AED(s)) for 28 days prior to screening and duration of trial Acceptable candidate for venipuncture and intravenous (iv) infusion At least 1 partial seizure with motor component per 90 days Maximum allowed seizure frequency during 28 days prior to screening is 40 partial seizures of any type Exclusion Criteria: Previous use of lacosamide History of primary generalized seizures History of status epilepticus within last 12 months History of cluster seizures during 8 week period prior to screening Non-epileptic events, including psychogenic seizures that could be confused with seizures Use of neuroleptics, monoamine oxidase (MAO) inhibitors, barbiturates, or narcotic analgesics within 28 days prior to screening Received any rescue benzodiazepines more than once during the 28 days prior to screening Concomitant treatment of felbamate or previous felbamate therapy within last 6 months Prior or concomitant vigabatrin use

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lacosamide 200 mg cohort<br>Single loading dose of intravenous (iv) lacosamide 200 mg followed by 6.5 days of oral lacosamide 100 mg twice daily | Drug: lacosamide<br>* Single loading intravenous (iv) lacosamide 200 mg dose administered over a 15 minute infusion duration followed by oral lacosamide 200 mg/day (100 mg twice daily) for 6.5 days<br>* Other names: Vimpat;|
| Experimental: Lacosamide 300 mg combined cohorts<br>Single loading dose of intravenous (iv) lacosamide 300 mg dose followed by 6.5 days of oral lacosamide 150 mg twice daily | Drug: lacosamide<br>* Single loading intravenous (iv) lacosamide 300 mg dose administered over a 15 minute infusion duration followed by oral lacosamide 300 mg/day (150 mg twice daily) for 6.5 days<br>* Other names: Vimpat;|
| Experimental: Lacosamide 400 mg cohort<br>Single loading dose of intravenous (iv) lacosamide 400 mg followed by 6.5 days of oral lacosamide 200 mg twice daily | Drug: lacosamide<br>* Single loading intravenous (iv) lacosamide 400 mg dose administered over a 15 minute infusion duration followed by oral lacosamide 400 mg/day (200 mg twice daily) for 6.5 days<br>* Other names: Vimpat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With at Least One Adverse Event During the Treatment Period (up to 7 Days) | An Adverse Event (AE) is any untoward medical occurrence (eg, noxious or pathological changes) in a subject or clinical investigation subject compared with pre-existing conditions, that occurs during any period of a clinical trial including Pre-treatment, Run-In, Wash-Out, or Follow-Up Periods. An AE is defined as being independent of assumption of any causality (eg, to study or concomitant medication, primary or concomitant disease, or study design). | Treatment period (up to 7 days) | 
| Number of Subjects Who Withdrew From the Trial Due to an Adverse Event | An Adverse Event (AE) is any untoward medical occurrence (eg, noxious or pathological changes) in a subject or clinical investigation subject compared with pre-existing conditions, that occurs during any period of a clinical trial including Pre-treatment, Run-In, Wash-Out, or Follow-Up Periods. An AE is defined as being independent of assumption of any causality (eg, to study or concomitant medication, primary or concomitant disease, or study design). | Entire trial period (up to 6 weeks), screening through safety follow-up period (2 weeks post last medication) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With at Least One Adverse Event With an Onset Within 4 Hours of Start of Infusion | An Adverse Event (AE) is any untoward medical occurrence (eg, noxious or pathological changes) in a subject or clinical investigation subject compared with pre-existing conditions, that occurs during any period of a clinical trial including Pre-treatment, Run-In, Wash-Out, or Follow-Up Periods. An AE is defined as being independent of assumption of any causality (eg, to study or concomitant medication, primary or concomitant disease, or study design). | 0-4 hours post start of the infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epilepsy, seizures, Lacosamide, Vimpat, intravenous