Epilepsy
Conditions
Keywords
Levetiracetam, Epilepsy, Children, Adults
Brief summary
To study how the body absorbs, distributes, metabolises and eliminates Keppra XR in both children (12 to 16 years old) and adults (18 to 55 years old) with epilepsy.
Interventions
DRUGKeppra XR
Keppra XR 500 mg tablets and Keppra XR 750 mg tablets Dosage: Keppra XR 1000-3000 mg/day taken once daily. Duration: 4-7 days
Sponsors
UCB BIOSCIENCES, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of epilepsy on up to three concomitant anti-epileptic drugs * Subjects on levetiracetam immediate release (IR) can be enrolled if on a stable dose for 7 days
Exclusion criteria
* Subjects with a history of status epilepticus within 3 months of Visit 1 * Subject has difficult venous accessibility
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration at Steady State (Cmax) of Keppra XR Normalized by Dose and by Body Weight and Dose During up to 7 Days of Administration | 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration. | The Cmax is the maximum plasma concentration normalized by dose and by body weight and dose. Cmax normalized by 1000 mg dose was calculated as: Cmax/(mg dose taken/ 1000 mg Keppra XR). Cmax normalized by body weight and dose (1 mg Keppra XR/kg) was calculated as: Cmax/(bodyweight (kg)/ mg dose Keppra XR taken). Pharmacokonetic (PK) samples were taken predose and 1h, 2.5h, 4h, 6h and 10h after study medication at day 4, 5, 6 or 7 of Keppra XR administration. |
| Area Under the Plasma Concentration Curve Over a Dosing Interval of 24 Hours (AUCtau) of Keppra XR Normalized by Dose, and by Body Weight and Dose During up to 7 Days of Administration | 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration. | AUCtau normalized by 1000 mg dose was calculated as: AUCtau/(mg dose taken/ 1000 mg Keppra XR). AUCtau normalized by body weight and dose (1 mg Keppra XR/kg) was calculated as: AUCtau/(bodyweight (kg)/ mg dose Keppra XR taken). 6 PK samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration. At steady state, reached after 2 days of administration of Keppra XR, the concentrations at 24h postdose is equal to the predose concentration. The predose concentration was used as the 24h concentration to calculate AUCτau. |
| Time of Maximum Plasma Concentration (Tmax) of Keppra XR During up to 7 Days of Administration | 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration. | The Tmax is the time corresponding to the maximum plasma concentration of Keppra XR. It was directly obtained from the observed concentration versus time curve. 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration. |
| Apparent Total Body Clearance (CL/F) of Keppra XR During up to 7 Days of Administration | 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration. | The Apparent Total Body Clearance (CL/F) was calculated as Dose/ AUCtau. 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days | From Starting Study Drug Treatment (Day 1) to up to 14 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. Treatment emergent means that an AE has begun or got worse after start of Keppra XR administration. |
Countries
United States
Participant flow
Recruitment details
Intent-to-treat (ITT) population includes all enrolled patients who received at least one dose of study medication.Pharmacokinetic Per-Protocol (PK-PP) population is a subset of the ITT population, consisting of those patients who had no major protocol deviations affecting the pharmacokinetic parameters.
Pre-assignment details
Participant Flow and Baseline characteristics refer to the Intention-to-treat (ITT) population.
Participants by arm
| Arm | Count |
|---|---|
| Keppra XR in Children (12-16 Years Old) Drug: Keppra XR
Keppra XR 500 mg tablets and Keppra XR 750 mg tablets
Dosage: Keppra XR 1000-3000 mg/day taken once daily
Duration: 4-7 days | 12 |
| Keppra XR in Adults (18-55 Years Old) Drug: Keppra XR
Keppra XR 500 mg tablets and Keppra XR 750 mg tablets
Dosage: Keppra XR 1000-3000 mg/day taken once daily
Duration: 4-7 days | 13 |
| Total | 25 |
Baseline characteristics
| Characteristic | Keppra XR in Children (12-16 Years Old) | Keppra XR in Adults (18-55 Years Old) | Total |
|---|---|---|---|
| Age, Continuous | 14.88 years STANDARD_DEVIATION 1.37 | 41.78 years STANDARD_DEVIATION 9.21 | 28.87 years STANDARD_DEVIATION 15.21 |
| Body Mass Index (BMI) | 27.62 kg/m^2 STANDARD_DEVIATION 7.01 | 28.63 kg/m^2 STANDARD_DEVIATION 7.14 | 28.14 kg/m^2 STANDARD_DEVIATION 6.95 |
| Body Surface Area (BSA) | 1.87 m^2 STANDARD_DEVIATION 0.34 | 1.95 m^2 STANDARD_DEVIATION 0.32 | 1.91 m^2 STANDARD_DEVIATION 0.32 |
| Height | 165.9 centimeter (cm) STANDARD_DEVIATION 8.8 | 169.3 centimeter (cm) STANDARD_DEVIATION 10.3 | 167.7 centimeter (cm) STANDARD_DEVIATION 9.6 |
| Race Black | 4 Participants | 3 Participants | 7 Participants |
| Race Caucasian | 8 Participants | 9 Participants | 17 Participants |
| Race Other / mixed | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
| Weight | 77.2 kilogram (kg) STANDARD_DEVIATION 24.1 | 82.5 kilogram (kg) STANDARD_DEVIATION 23 | 80.0 kilogram (kg) STANDARD_DEVIATION 23.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 12 | 3 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 |
Outcome results
Primary
Apparent Total Body Clearance (CL/F) of Keppra XR During up to 7 Days of Administration
The Apparent Total Body Clearance (CL/F) was calculated as Dose/ AUCtau. 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration.
Time frame: 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration.
Population: PK-PP population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Keppra XR in Children (12-16 Years Old) | Apparent Total Body Clearance (CL/F) of Keppra XR During up to 7 Days of Administration | 3.78 L/h | Geometric Coefficient of Variation 31.4 |
| Keppra XR in Adults (18-55 Years Old) | Apparent Total Body Clearance (CL/F) of Keppra XR During up to 7 Days of Administration | 4.23 L/h | Geometric Coefficient of Variation 41.8 |
Primary
Area Under the Plasma Concentration Curve Over a Dosing Interval of 24 Hours (AUCtau) of Keppra XR Normalized by Dose, and by Body Weight and Dose During up to 7 Days of Administration
AUCtau normalized by 1000 mg dose was calculated as: AUCtau/(mg dose taken/ 1000 mg Keppra XR). AUCtau normalized by body weight and dose (1 mg Keppra XR/kg) was calculated as: AUCtau/(bodyweight (kg)/ mg dose Keppra XR taken). 6 PK samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration. At steady state, reached after 2 days of administration of Keppra XR, the concentrations at 24h postdose is equal to the predose concentration. The predose concentration was used as the 24h concentration to calculate AUCτau.
Time frame: 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration.
Population: Pharmacokinetic Per-Protocol (PK-PP) population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Keppra XR in Children (12-16 Years Old) | Area Under the Plasma Concentration Curve Over a Dosing Interval of 24 Hours (AUCtau) of Keppra XR Normalized by Dose, and by Body Weight and Dose During up to 7 Days of Administration | Dose norm. (Keppra XR 1000mg) | 265 µg*h/mL |
| Keppra XR in Children (12-16 Years Old) | Area Under the Plasma Concentration Curve Over a Dosing Interval of 24 Hours (AUCtau) of Keppra XR Normalized by Dose, and by Body Weight and Dose During up to 7 Days of Administration | Dose and weight norm. (Keppra XR 1 mg/kg) | 19.4 µg*h/mL |
| Keppra XR in Adults (18-55 Years Old) | Area Under the Plasma Concentration Curve Over a Dosing Interval of 24 Hours (AUCtau) of Keppra XR Normalized by Dose, and by Body Weight and Dose During up to 7 Days of Administration | Dose norm. (Keppra XR 1000mg) | 236 µg*h/mL |
| Keppra XR in Adults (18-55 Years Old) | Area Under the Plasma Concentration Curve Over a Dosing Interval of 24 Hours (AUCtau) of Keppra XR Normalized by Dose, and by Body Weight and Dose During up to 7 Days of Administration | Dose and weight norm. (Keppra XR 1 mg/kg) | 19.6 µg*h/mL |
Comparison: An ANOVA for log-transformed values has been used as the basis for calculation of point estimates and Confidence Intervals (CIs).90% CI: [0.811, 1.2118]ANOVA
Primary
Maximum Concentration at Steady State (Cmax) of Keppra XR Normalized by Dose and by Body Weight and Dose During up to 7 Days of Administration
The Cmax is the maximum plasma concentration normalized by dose and by body weight and dose. Cmax normalized by 1000 mg dose was calculated as: Cmax/(mg dose taken/ 1000 mg Keppra XR). Cmax normalized by body weight and dose (1 mg Keppra XR/kg) was calculated as: Cmax/(bodyweight (kg)/ mg dose Keppra XR taken). Pharmacokonetic (PK) samples were taken predose and 1h, 2.5h, 4h, 6h and 10h after study medication at day 4, 5, 6 or 7 of Keppra XR administration.
Time frame: 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration.
Population: Pharmacokinetic Per-Protocol (PK-PP) population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Keppra XR in Children (12-16 Years Old) | Maximum Concentration at Steady State (Cmax) of Keppra XR Normalized by Dose and by Body Weight and Dose During up to 7 Days of Administration | Dose norm. ( Keppra XR 1000mg) | 17.3 µg/mL |
| Keppra XR in Children (12-16 Years Old) | Maximum Concentration at Steady State (Cmax) of Keppra XR Normalized by Dose and by Body Weight and Dose During up to 7 Days of Administration | Dose and weight norm. ( Keppra XR 1 mg/kg) | 1.27 µg/mL |
| Keppra XR in Adults (18-55 Years Old) | Maximum Concentration at Steady State (Cmax) of Keppra XR Normalized by Dose and by Body Weight and Dose During up to 7 Days of Administration | Dose norm. ( Keppra XR 1000mg) | 14.9 µg/mL |
| Keppra XR in Adults (18-55 Years Old) | Maximum Concentration at Steady State (Cmax) of Keppra XR Normalized by Dose and by Body Weight and Dose During up to 7 Days of Administration | Dose and weight norm. ( Keppra XR 1 mg/kg) | 1.24 µg/mL |
Comparison: An ANOVA for log-transformed values has been used as the basis for calculation of point estimates and Confidence Intervals (CIs).90% CI: [0.8817, 1.1964]ANOVA
Primary
Time of Maximum Plasma Concentration (Tmax) of Keppra XR During up to 7 Days of Administration
The Tmax is the time corresponding to the maximum plasma concentration of Keppra XR. It was directly obtained from the observed concentration versus time curve. 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration.
Time frame: 6 pharmacokinetic samples were taken pre-dose, 1, 2.5, 4, 6 and 10 hours after administration, at Day 4, 5, 6, or 7 of Keppra XR administration.
Population: PK-PP population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Keppra XR in Children (12-16 Years Old) | Time of Maximum Plasma Concentration (Tmax) of Keppra XR During up to 7 Days of Administration | 5.90 hours (h) |
| Keppra XR in Adults (18-55 Years Old) | Time of Maximum Plasma Concentration (Tmax) of Keppra XR During up to 7 Days of Administration | 5.93 hours (h) |
Secondary
Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 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. Treatment emergent means that an AE has begun or got worse after start of Keppra XR administration.
Time frame: From Starting Study Drug Treatment (Day 1) to up to 14 days
Population: Safety Set includes all subjects who took at least one dose of study medication. The Safety Set is identical to the Intention-to-treat (ITT) population in this study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Keppra XR in Children (12-16 Years Old) | Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days | Total number of AEs | 7 Count |
| Keppra XR in Children (12-16 Years Old) | Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days | Patients with at least 1 AE | 3 Count |
| Keppra XR in Children (12-16 Years Old) | Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days | Patients with severe AEs | 0 Count |
| Keppra XR in Children (12-16 Years Old) | Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days | Patients with serious AEs | 0 Count |
| Keppra XR in Adults (18-55 Years Old) | Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days | Patients with serious AEs | 0 Count |
| Keppra XR in Adults (18-55 Years Old) | Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days | Total number of AEs | 11 Count |
| Keppra XR in Adults (18-55 Years Old) | Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days | Patients with severe AEs | 1 Count |
| Keppra XR in Adults (18-55 Years Old) | Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days | Patients with at least 1 AE | 3 Count |