Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 68 of 146 for:    epilepsy AND Bethesda

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00961441
Recruitment Status : Completed
First Posted : August 19, 2009
Results First Posted : May 25, 2011
Last Update Posted : August 6, 2015
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Epilepsy
Intervention Drug: Keppra XR
Enrollment 25
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.
Arm/Group Title Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Hide Arm/Group Description

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

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

Period Title: Overall Study
Started 12 13
Pharmacokinetic (PK-PP) Population 12 10 [1]
Completed 12 13
Not Completed 0 0
[1]
Two subjects were excluded due to study medication noncompliance, one due to wrong dosing regimen.
Arm/Group Title Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old) Total
Hide Arm/Group Description

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

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 of all reporting groups
Overall Number of Baseline Participants 12 13 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 13 participants 25 participants
14.88  (1.37) 41.78  (9.21) 28.87  (15.21)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 13 participants 25 participants
Female
6
  50.0%
8
  61.5%
14
  56.0%
Male
6
  50.0%
5
  38.5%
11
  44.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 12 participants 13 participants 25 participants
77.2  (24.1) 82.5  (23.0) 80.0  (23.2)
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 12 participants 13 participants 25 participants
165.9  (8.8) 169.3  (10.3) 167.7  (9.6)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 12 participants 13 participants 25 participants
27.62  (7.01) 28.63  (7.14) 28.14  (6.95)
Body Surface Area (BSA)  
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 12 participants 13 participants 25 participants
1.87  (0.34) 1.95  (0.32) 1.91  (0.32)
Race  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 13 participants 25 participants
Black 4 3 7
Caucasian 8 9 17
Other / mixed 0 1 1
1.Primary Outcome
Title 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
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Per-Protocol (PK-PP) population
Arm/Group Title Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 12 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
Dose norm. ( Keppra XR 1000mg)
17.3
(14.3 to 21.0)
14.9
(12.1 to 18.5)
Dose and weight norm. ( Keppra XR 1 mg/kg)
1.27
(1.12 to 1.44)
1.24
(1.08 to 1.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Keppra XR in Children (12-16 Years Old), Keppra XR in Adults (18-55 Years Old)
Comments An ANOVA for log-transformed values has been used as the basis for calculation of point estimates and Confidence Intervals (CIs).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Point estimates for the geometric means ratios children/adults for Cmax normalized by dose and body weight and 90% CIs have been calculated.
Method of Estimation Estimation Parameter Point estimate for ratio
Estimated Value 1.0271
Confidence Interval (2-Sided) 90%
0.8817 to 1.1964
Estimation Comments [Not Specified]
2.Primary Outcome
Title 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
Hide Description

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.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Per-Protocol (PK-PP) population
Arm/Group Title Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 12 10
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg*h/mL
Dose norm. (Keppra XR 1000mg)
265
(214 to 327)
236
(187 to 298)
Dose and weight norm. (Keppra XR 1 mg/kg)
19.4
(16.5 to 22.9)
19.6
(16.4 to 23.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Keppra XR in Children (12-16 Years Old), Keppra XR in Adults (18-55 Years Old)
Comments An ANOVA for log-transformed values has been used as the basis for calculation of point estimates and Confidence Intervals (CIs).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Point estimates for the geometric means ratios children/adults for AUCtau normalized by dose and body weight and 90% CIs have been calculated.
Method of Estimation Estimation Parameter Point estimate for ratio
Estimated Value 0.9914
Confidence Interval (2-Sided) 90%
0.8110 to 1.2118
Estimation Comments [Not Specified]
3.Primary Outcome
Title Time of Maximum Plasma Concentration (Tmax) of Keppra XR During up to 7 Days of Administration
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
PK-PP population
Arm/Group Title Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 12 10
Median (Full Range)
Unit of Measure: hours (h)
5.90
(2.50 to 6.07)
5.93
(2.45 to 6.05)
4.Primary Outcome
Title Apparent Total Body Clearance (CL/F) of Keppra XR During up to 7 Days of Administration
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
PK-PP population
Arm/Group Title Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 12 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
3.78
(31.4%)
4.23
(41.8%)
5.Secondary Outcome
Title Occurrence of Treatment-Emergent Adverse Events From Starting Study Drug Treatment (Day 1) to up to 14 Days
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 12 13
Measure Type: Number
Unit of Measure: Count
Total number of AEs 7 11
Patients with at least 1 AE 3 3
Patients with severe AEs 0 1
Patients with serious AEs 0 0
Time Frame From Starting Study Drug Treatment (Day 1) to up to 14 days.
Adverse Event Reporting Description 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.
 
Arm/Group Title Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Hide Arm/Group Description

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

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

All-Cause Mortality
Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/12 (0.00%)      0/13 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Keppra XR in Children (12-16 Years Old) Keppra XR in Adults (18-55 Years Old)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/12 (25.00%)      3/13 (23.08%)    
Blood and lymphatic system disorders     
Lymphadenopathy * 1  1/12 (8.33%)  1 0/13 (0.00%)  0
Gastrointestinal disorders     
Nausea * 1  1/12 (8.33%)  1 1/13 (7.69%)  1
Vomiting * 1  1/12 (8.33%)  1 1/13 (7.69%)  2
General disorders     
Fatigue * 1  1/12 (8.33%)  1 0/13 (0.00%)  0
Irritability * 1  0/12 (0.00%)  0 1/13 (7.69%)  1
Infections and infestations     
Pharyngitis streptococcal * 1  1/12 (8.33%)  1 0/13 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  0/12 (0.00%)  0 1/13 (7.69%)  1
Nervous system disorders     
Somnolence * 1  1/12 (8.33%)  1 1/13 (7.69%)  1
Paraesthesia * 1  0/12 (0.00%)  0 1/13 (7.69%)  1
Psychiatric disorders     
Abnormal behaviour * 1  1/12 (8.33%)  1 0/13 (0.00%)  0
Reproductive system and breast disorders     
Dysmenorrhoea * 1  0/12 (0.00%)  0 1/13 (7.69%)  1
Skin and subcutaneous tissue disorders     
Hypoaesthesia facial * 1  0/12 (0.00%)  0 1/13 (7.69%)  1
Pruritus * 1  0/12 (0.00%)  0 1/13 (7.69%)  1
Rash * 1  0/12 (0.00%)  0 1/13 (7.69%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
UCB has > 60 days but <= 180 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB Clinical Trial Call Center
Organization: UCB
Phone: +1 877 822 9493 (UCB)
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB BIOSCIENCES, Inc. )
ClinicalTrials.gov Identifier: NCT00961441     History of Changes
Other Study ID Numbers: N01340
2014-004376-39 ( EudraCT Number )
First Submitted: August 17, 2009
First Posted: August 19, 2009
Results First Submitted: March 15, 2011
Results First Posted: May 25, 2011
Last Update Posted: August 6, 2015