Epilepsy, Partial Onset Seizures
Conditions
Keywords
Levetiracetam, Infusion, Epilepsy, Partial Onset Seizures
Brief summary
To evaluate the safety of Levetiracetam IV 15-minute infusion administered every 12 hours as adjunctive treatment in subjects with Partial Onset Seizures after switching from the equivalent Levetiracetam oral dose.
Interventions
DRUGLevetiracetam
* Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Sponsors
UCB Japan Co. Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is a male or female aged ≥ 16 years * Subject has Partial Onset Seizures that are classifiable according to the 1981 International League Against Epilepsy (ILAE) classification of Epileptic Seizures * Subject weighs ≥ 40 kg * Subject is currently taking Levetiracetam (LEV) as an adjunctive antiepileptic oral treatment with 1 to 3 other Antiepileptic Drugs (AEDs)
Exclusion criteria
* Subject has problems with venous accessibility * Subject has participated in another clinical/pharmacological study during the last 4 weeks prior to the Screening Visit * Subject is pregnant or lactating * Subject has a history of suicide attempt(s) or presents with current depressive signs, current suicidal ideation, and/or behavior * Subject has clinically significant Electrocardiogram (ECG) abnormalities according to the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events During the Entire Study Period (up to 32 Days) | During the entire Study Period from Screening (Day -14 to Day -1) over Evaluation Period (Day 1 to Day 4) to Follow-Up Period (Day 5 to Day 18) | An Adverse Event (AE) is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Incidence of Treatment Emergent Serious Adverse Events During the Entire Study Period (up to 32 Days) | During the entire Study Period from Screening (Day -14 to Day -1) over Evaluation Period (Day 1 to Day 4) to Follow-Up Period (Day 5 to Day 18) | A Serious Adverse Event (SAE) is any untoward medical occurrence that results in death, is life-threatening, results in significant or persistent disability/incapacity, is a congenital anomaly/birth defect (including that occurring in a fetus), or is an important medical event that may jeopardize the subject or may require medical or surgical intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Normalized Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 1 | Day 1 | Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 1. Plasma trough concentration (Ctrough) was normalized to a dose of 500 mg as follows: Dose normalized Ctrough = Ctrough/last dose \[mg\] x 500 mg. |
| Observed Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 1 | Day 1 | Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 1. |
| Partial (Type 1) Seizure Frequency Per Day Over the Evaluation Period | During the Evaluation Period (Day 1 to Day 4) | Partial (Type I) seizures can be classified into one of the following three groups: Simple partial seizures, Complex partial seizures, Partial seizures evolving to secondarily generalized seizures. |
| Dose Normalized Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 4 | Day 4 | Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 4. Plasma trough concentration (Ctrough) was normalized to a dose of 500 mg as follows: Dose normalized Ctrough = Ctrough/last dose \[mg\] x 500 mg. |
| Observed Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 4 | Day 4 | Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 4. |
Countries
Japan
Participant flow
Recruitment details
This study started to enroll subjects in July 2011 in order to end up with 4 centers in Japan. 16 subjects were treated and completed the study. All 16 subjects are included in the Safety Set.
Pre-assignment details
The Safety Set (SS) consisted of all subjects who started Levetiracetam intravenous (LEV IV) infusion after they had signed and dated the Informed Consent form. Participant Flow and Baseline Characteristics refer to the Safety Set (SS).
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam.
Levetiracetam :
* Formulation: concentrate for solution for infusion
* Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL)
* Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day
* Frequency: twice daily | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Levetiracetam |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age Continuous | 32.9 years STANDARD_DEVIATION 10.6 |
| Height | 163.40 centimeter STANDARD_DEVIATION 8.95 |
| Region of Enrollment Japan | 16 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
| Weight | 68.82 kilogram STANDARD_DEVIATION 12.38 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Incidence of Treatment Emergent Adverse Events During the Entire Study Period (up to 32 Days)
An Adverse Event (AE) is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: During the entire Study Period from Screening (Day -14 to Day -1) over Evaluation Period (Day 1 to Day 4) to Follow-Up Period (Day 5 to Day 18)
Population: Safety Set (SS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Incidence of Treatment Emergent Adverse Events During the Entire Study Period (up to 32 Days) | 5 participants |
Primary
Incidence of Treatment Emergent Serious Adverse Events During the Entire Study Period (up to 32 Days)
A Serious Adverse Event (SAE) is any untoward medical occurrence that results in death, is life-threatening, results in significant or persistent disability/incapacity, is a congenital anomaly/birth defect (including that occurring in a fetus), or is an important medical event that may jeopardize the subject or may require medical or surgical intervention.
Time frame: During the entire Study Period from Screening (Day -14 to Day -1) over Evaluation Period (Day 1 to Day 4) to Follow-Up Period (Day 5 to Day 18)
Population: Safety Set (SS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam | Incidence of Treatment Emergent Serious Adverse Events During the Entire Study Period (up to 32 Days) | 0 participants |
Secondary
Dose Normalized Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 1
Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 1. Plasma trough concentration (Ctrough) was normalized to a dose of 500 mg as follows: Dose normalized Ctrough = Ctrough/last dose \[mg\] x 500 mg.
Time frame: Day 1
Population: Pharmacokinetic Per Protocol Set (PK-PPS). This was defined as a subset of the Safety Set (SS) and consisted of subjects who had at least 1 evaluable Levetiracetam plasma concentration after intravenous administration. All 16 subjects from the SS are included in the PK-PPS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | Dose Normalized Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 1 | 6.611 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 29.6 |
Secondary
Dose Normalized Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 4
Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 4. Plasma trough concentration (Ctrough) was normalized to a dose of 500 mg as follows: Dose normalized Ctrough = Ctrough/last dose \[mg\] x 500 mg.
Time frame: Day 4
Population: Pharmacokinetic Per Protocol Set (PK-PPS). This was defined as a subset of the Safety Set (SS) and consisted of subjects who had at least 1 evaluable Levetiracetam plasma concentration after intravenous administration. All 16 subjects from the SS are included in the PK-PPS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | Dose Normalized Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 4 | 5.492 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 29.4 |
Secondary
Observed Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 1
Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 1.
Time frame: Day 1
Population: Pharmacokinetic Per Protocol Set (PK-PPS). This was defined as a subset of the Safety Set (SS) and consisted of subjects who had at least 1 evaluable Levetiracetam plasma concentration after intravenous administration. All 16 subjects from the SS are included in the PK-PPS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | Observed Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 1 | 11.732 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 63.1 |
Secondary
Observed Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 4
Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 4.
Time frame: Day 4
Population: Pharmacokinetic Per Protocol Set (PK-PPS). This was defined as a subset of the Safety Set (SS) and consisted of subjects who had at least 1 evaluable Levetiracetam plasma concentration after intravenous administration. All 16 subjects from the SS are included in the PK-PPS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam | Observed Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 4 | 11.632 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 59.6 |
Secondary
Partial (Type 1) Seizure Frequency Per Day Over the Evaluation Period
Partial (Type I) seizures can be classified into one of the following three groups: Simple partial seizures, Complex partial seizures, Partial seizures evolving to secondarily generalized seizures.
Time frame: During the Evaluation Period (Day 1 to Day 4)
Population: Full Analysis Set (FAS). The FAS consisted of all subjects in the Safety Set (SS) with evaluable seizure frequency data over the Evaluation Period. All 16 subjects in the SS are included in the FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Levetiracetam | Partial (Type 1) Seizure Frequency Per Day Over the Evaluation Period | 0.38 Seizures per day |