Partial Epilepsies, Partial Onset Seizures
Conditions
Keywords
epilepsy, seizures, Lacosamide, Vimpat, intravenous
Brief summary
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
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.
Interventions
DRUGlacosamide
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
Sponsors
UCB BIOSCIENCES, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least One Adverse Event During the Treatment Period (up to 7 Days) | 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). |
| Number of Subjects Who Withdrew From the Trial Due to an Adverse Event | Entire trial period (up to 6 weeks), screening through safety follow-up period (2 weeks post last medication) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least One Adverse Event With an Onset Within 4 Hours of Start of Infusion | 0-4 hours post start of the 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lacosamide (200 mg) Single loading dose of intravenous (iv) lacosamide 200 mg followed by 6.5 days of oral lacosamide 100 mg twice daily | 25 |
| Lacosamide (300 mg) Single loading dose of intravenous (iv) lacosamide 300 mg dose followed by 6.5 days of oral lacosamide 150 mg twice daily | 50 |
| Lacosamide (400 mg) Single loading dose of intravenous (iv) lacosamide 400 mg followed by 6.5 days of oral lacosamide 200 mg twice daily | 25 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| All Periods Combined | Adverse Event | 0 | 3 | 4 |
| Period 2 (up to 7 Days) | Adverse Event | 0 | 1 | 0 |
| Period 3 (up to 7 Days) | Adverse Event | 0 | 0 | 4 |
| Period 4 (up to 7 Days) | Adverse Event | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Lacosamide (300 mg) | Lacosamide (400 mg) | Lacosamide (200 mg) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 25 Participants | 25 Participants | 98 Participants |
| Age, Continuous | 38.6 years STANDARD_DEVIATION 11.53 | 39.6 years STANDARD_DEVIATION 12.24 | 39.1 years STANDARD_DEVIATION 11.77 | 39.0 years STANDARD_DEVIATION 11.66 |
| Region of Enrollment United States | 50 participants | 25 participants | 25 participants | 100 participants |
| Sex: Female, Male Female | 26 Participants | 9 Participants | 14 Participants | 49 Participants |
| Sex: Female, Male Male | 24 Participants | 16 Participants | 11 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 25 | 37 / 50 | 20 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 50 | 1 / 25 |
Outcome results
Primary
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).
Time frame: Entire trial period (up to 6 weeks), screening through safety follow-up period (2 weeks post last medication)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lacosamide (200 mg) | Number of Subjects Who Withdrew From the Trial Due to an Adverse Event | 0 subjects |
| Lacosamide (300 mg) | Number of Subjects Who Withdrew From the Trial Due to an Adverse Event | 3 subjects |
| Lacosamide (400 mg) | Number of Subjects Who Withdrew From the Trial Due to an Adverse Event | 4 subjects |
Primary
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).
Time frame: Treatment period (up to 7 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lacosamide (200 mg) | Number of Subjects With at Least One Adverse Event During the Treatment Period (up to 7 Days) | 17 subjects |
| Lacosamide (300 mg) | Number of Subjects With at Least One Adverse Event During the Treatment Period (up to 7 Days) | 42 subjects |
| Lacosamide (400 mg) | Number of Subjects With at Least One Adverse Event During the Treatment Period (up to 7 Days) | 20 subjects |
Secondary
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).
Time frame: 0-4 hours post start of the infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lacosamide (200 mg) | Number of Subjects With at Least One Adverse Event With an Onset Within 4 Hours of Start of Infusion | 5 subjects |
| Lacosamide (300 mg) | Number of Subjects With at Least One Adverse Event With an Onset Within 4 Hours of Start of Infusion | 24 subjects |
| Lacosamide (400 mg) | Number of Subjects With at Least One Adverse Event With an Onset Within 4 Hours of Start of Infusion | 16 subjects |