Trial Outcomes & Findings for Study Evaluating the Pharmacokinetics of Keppra Extended Release (XR) in Children and Adults With Epilepsy (NCT NCT00961441)

Last Updated: 2015-08-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

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.

Results posted on

2015-08-06

Participant Flow

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.

Participant Flow and Baseline characteristics refer to the Intention-to-treat (ITT) population.

Participant milestones

Participant milestones
Measure	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	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
Overall Study STARTED	12	13
Overall Study Pharmacokinetic (PK-PP) Population	12	10
Overall Study COMPLETED	12	13
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study Evaluating the Pharmacokinetics of Keppra Extended Release (XR) in Children and Adults With Epilepsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Keppra XR in Children (12-16 Years Old) n=12 Participants 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	Keppra XR in Adults (18-55 Years Old) n=13 Participants 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	Total n=25 Participants Total of all reporting groups
Age, Continuous	14.88 years STANDARD_DEVIATION 1.37 • n=5 Participants	41.78 years STANDARD_DEVIATION 9.21 • n=7 Participants	28.87 years STANDARD_DEVIATION 15.21 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Weight	77.2 kilogram (kg) STANDARD_DEVIATION 24.1 • n=5 Participants	82.5 kilogram (kg) STANDARD_DEVIATION 23.0 • n=7 Participants	80.0 kilogram (kg) STANDARD_DEVIATION 23.2 • n=5 Participants
Height	165.9 centimeter (cm) STANDARD_DEVIATION 8.8 • n=5 Participants	169.3 centimeter (cm) STANDARD_DEVIATION 10.3 • n=7 Participants	167.7 centimeter (cm) STANDARD_DEVIATION 9.6 • n=5 Participants
Body Mass Index (BMI)	27.62 kg/m^2 STANDARD_DEVIATION 7.01 • n=5 Participants	28.63 kg/m^2 STANDARD_DEVIATION 7.14 • n=7 Participants	28.14 kg/m^2 STANDARD_DEVIATION 6.95 • n=5 Participants
Body Surface Area (BSA)	1.87 m^2 STANDARD_DEVIATION 0.34 • n=5 Participants	1.95 m^2 STANDARD_DEVIATION 0.32 • n=7 Participants	1.91 m^2 STANDARD_DEVIATION 0.32 • n=5 Participants
Race Black	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race Caucasian	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Race Other / mixed	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Keppra XR in Children (12-16 Years Old) n=12 Participants 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	Keppra XR in Adults (18-55 Years Old) n=10 Participants 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
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 Interval 14.3 to 21.0	14.9 µg/mL Interval 12.1 to 18.5
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 Interval 1.12 to 1.44	1.24 µg/mL Interval 1.08 to 1.42

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Keppra XR in Children (12-16 Years Old) n=12 Participants 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	Keppra XR in Adults (18-55 Years Old) n=10 Participants 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
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 Interval 214.0 to 327.0	236 µg*h/mL Interval 187.0 to 298.0
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 Interval 16.5 to 22.9	19.6 µg*h/mL Interval 16.4 to 23.5

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Keppra XR in Children (12-16 Years Old) n=12 Participants 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	Keppra XR in Adults (18-55 Years Old) n=10 Participants 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
Time of Maximum Plasma Concentration (Tmax) of Keppra XR During up to 7 Days of Administration	5.90 hours (h) Interval 2.5 to 6.07	5.93 hours (h) Interval 2.45 to 6.05

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Keppra XR in Children (12-16 Years Old) n=12 Participants 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	Keppra XR in Adults (18-55 Years Old) n=10 Participants 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
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	4.23 L/h Geometric Coefficient of Variation 41.8

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Keppra XR in Children (12-16 Years Old) n=12 Participants 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	Keppra XR in Adults (18-55 Years Old) n=13 Participants 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
Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days Total number of AEs	7 Count	11 Count
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	3 Count
Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days Patients with severe AEs	0 Count	1 Count
Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days Patients with serious AEs	0 Count	0 Count

Adverse Events

Keppra XR in Children (12-16 Years Old)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Keppra XR in Adults (18-55 Years Old)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Keppra XR in Children (12-16 Years Old) n=12 participants at risk 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	Keppra XR in Adults (18-55 Years Old) n=13 participants at risk 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
Nervous system disorders Somnolence	8.3% 1/12 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Nervous system disorders Paraesthesia	0.00% 0/12 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Gastrointestinal disorders Nausea	8.3% 1/12 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Gastrointestinal disorders Vomiting	8.3% 1/12 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 2 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
General disorders Fatigue	8.3% 1/12 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	0.00% 0/13 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
General disorders Irritability	0.00% 0/12 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Blood and lymphatic system disorders Lymphadenopathy	8.3% 1/12 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	0.00% 0/13 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Infections and infestations Pharyngitis streptococcal	8.3% 1/12 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	0.00% 0/13 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Psychiatric disorders Abnormal behaviour	8.3% 1/12 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	0.00% 0/13 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/12 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/12 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Skin and subcutaneous tissue disorders Hypoaesthesia facial	0.00% 0/12 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/12 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.
Skin and subcutaneous tissue disorders Rash	0.00% 0/12 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.	7.7% 1/13 • Number of events 1 • From Starting Study Drug Treatment (Day 1) to up to 14 days. Treatment-Emergent AEs were collected and refer to the Safety Set. Safety Set includes all subjects who took at least one dose of study medication. Treatment emergent means that an Adverse Event has begun or got worse after start of Keppra XR administration.

Additional Information

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