Open-label Study of Levetiracetam Intravenous Infusion in Children (1 Month-4 Years Old) With Epilepsy

• ClinicalTrials.gov Identifier: NCT00505934
• Recruitment Status: Completed
• First Posted: July 25, 2007
• Results First Posted: February 25, 2011
• Last Update Posted: July 15, 2015
• Sponsor: UCB Pharma SA
• Information provided by (Responsible Party): UCB Pharma ( UCB Pharma SA )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epilepsy
• Intervention: Drug: Levetiracetam
• Enrollment: 19

Participant Flow

Recruitment Details	Subjects were recruited from sites in the United States, Belgium, Germany, France, Mexico, and Turkey. The study began in May 2008 and continued until March 2010, with the last subject's visit occurring in March of 2010.
Pre-assignment Details	Participant Flow refers to the Intent-to-treat (ITT) Population, consisting of all subjects who received at least 1 dose of study medication.

Arm/Group Title	Levetiracetam
Arm/Group Description	Intravenous 100 mg/mL, twice a day, maximum of 4 days Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose within the following dose range, calculated on the basis of their age and weight:.; Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily);; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily).; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily).
Period Title: Overall Study
Started	19 [1]
Completed	16
Not Completed	3
Reason Not Completed
Adverse Event	1
Other: Unable to obtain IV & PK samples	1
Other: IV dose needed to be changed	1
[1] Of the 23 subjects screened, 19 were enrolled into the study and received levetiracetam IV (LEV IV).

Baseline Characteristics

Arm/Group Title		Levetiracetam
Arm/Group Description		Intravenous 100 mg/mL, twice a day, maximum of 4 days Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose within the following dose range, calculated on the basis of their age and weight:.; Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily);; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily).; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily).
Overall Number of Baseline Participants		19
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	<=18 years	19 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	19 participants
		1.59 (1.24)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Female	7 36.8%
	Male	12 63.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	19 participants
United States		7
Mexico		8
Belgium		1
Turkey		2
Germany		1

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Reporting at Least 1 Treatment-Emergent Adverse Event (TEAE) During the Treatment Period (up to 4 Days)
Description	[Not Specified]
Time Frame	Treatment period (up to 4 days)

Outcome Measure Data

Analysis Population Description

All 19 subjects enrolled in the study were included in the Intent to Treat (ITT) population and are included in this analysis.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Intravenous 100 mg/mL, twice a day, maximum of 4 days Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose within the following dose range, calculated on the basis of their age and weight:.; Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily);; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily).; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily).
Overall Number of Participants Analyzed	19
Measure Type: Number; Unit of Measure: Subjects
	12

2. Secondary Outcome

Title	Number of Subjects Who Received High-dose Levetiracetam Intravenous (LEV IV) (More Than 28 mg/kg/Day for Subjects <6 Months; >40mg/kg/Day for Subjects ≥6 Months) During the Treatment Period (up to 4 Days)
Description	[Not Specified]
Time Frame	Treatment period (up to 4 days)

Outcome Measure Data

Analysis Population Description

All 19 subjects enrolled in the study were included in the Intent to Treat (ITT) population and are included in this analysis.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Intravenous 100 mg/mL, twice a day, maximum of 4 days Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose within the following dose range, calculated on the basis of their age and weight:.; Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily);; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily).; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily).
Overall Number of Participants Analyzed	19
Measure Type: Number; Unit of Measure: Subjects
	6

3. Secondary Outcome

Title	Number of Consecutive Levetiracetam Intravenous (LEV IV) Doses Received
Description	[Not Specified]
Time Frame	Treatment period (up to 4 days)

Outcome Measure Data

Analysis Population Description

All 19 subjects enrolled in the study were included in the Intent to Treat (ITT) population and are included in this analysis.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Intravenous 100 mg/mL, twice a day, maximum of 4 days Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose within the following dose range, calculated on the basis of their age and weight:.; Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily);; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily).; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily).
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: Consecutive doses
	2.89 (1.41)

Adverse Events

Time Frame	Up to 4 days
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Levetiracetam
Arm/Group Description	Intravenous 100 mg/mL, twice a day, maximum of 4 days Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose within the following dose range, calculated on the basis of their age and weight:.; Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily);; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily).; Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily).
All-Cause Mortality
	Levetiracetam
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	4/19 (21.05%)
Cardiac disorders
BRADYCARDIA * 1	1/19 (5.26%)	1
CARDIAC ARREST * 1	1/19 (5.26%)	1
General disorders
PYREXIA * 1	1/19 (5.26%)	1
Infections and infestations
PNEUMONIA * 1	2/19 (10.53%)	3
ABDOMINAL SEPSIS * 1	1/19 (5.26%)	1
Investigations
ELECTROCARDIOGRAM QT PROLONGED * 1	1/19 (5.26%)	1
Metabolism and nutrition disorders
METABOLIC ACIDOSIS * 1	2/19 (10.53%)	2
Nervous system disorders
CONVULSION * 1	1/19 (5.26%)	1
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE * 1	1/19 (5.26%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (9.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	10/19 (52.63%)
Cardiac disorders
BRADYCARDIA * 1	1/19 (5.26%)	1
Eye disorders
EYE SWELLING * 1	1/19 (5.26%)	1
Gastrointestinal disorders
VOMITING * 1	1/19 (5.26%)	1
General disorders
PYREXIA * 1	2/19 (10.53%)	2
IRRITABILITY * 1	1/19 (5.26%)	1
PAIN * 1	1/19 (5.26%)	1
PUNCTURE SITE PAIN * 1	1/19 (5.26%)	1
Injury, poisoning and procedural complications
PROCEDURAL PAIN * 1	1/19 (5.26%)	1
Investigations
ELECTROENCEPHALOGRAM * 1	1/19 (5.26%)	1
Nervous system disorders
SOMNOLENCE * 1	1/19 (5.26%)	3
DROOLING * 1	1/19 (5.26%)	1
MYOCLONIC EPILEPSY * 1	1/19 (5.26%)	1
Psychiatric disorders
RESTLESSNESS * 1	1/19 (5.26%)	1
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA * 1	1/19 (5.26%)	1
Skin and subcutaneous tissue disorders
PETECHIAE * 1	1/19 (5.26%)	1
NEURODERMATITIS * 1	1/19 (5.26%)	1
Vascular disorders
HYPOTENSION * 1	2/19 (10.53%)	2
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (9.0)

Limitations and Caveats

[Not Specified]

More Information

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 is confidential and 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

• Name/Title: UCB Clinical Trial Call Center
• Organization: UCB
• Phone: +1 877 822 9493

Publications of Results:

Weinstock A, Ruiz M, Gerard D, Toublanc N, Stockis A, Farooq O, Dilley D, Karmon Y, Elgie MJ, Schiemann-Delgado J. Prospective Open-Label, Single-Arm, Multicenter, Safety, Tolerability, and Pharmacokinetic Studies of Intravenous Levetiracetam in Children With Epilepsy. J Child Neurol. 2013 Nov;28(11):1423-1429. doi: 10.1177/0883073813480241. Epub 2013 Mar 26.

• Responsible Party: UCB Pharma ( UCB Pharma SA )
• ClinicalTrials.gov Identifier: NCT00505934
• Other Study ID Numbers: N01275; 2007-003517-13 ( EudraCT Number )
• First Submitted: July 20, 2007
• First Posted: July 25, 2007
• Results First Submitted: January 28, 2011
• Results First Posted: February 25, 2011
• Last Update Posted: July 15, 2015