Open-label Study of Levetiracetam Intravenous Infusion in Children (4-16 Years Old) With Epilepsy

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00535392
• Collaborator: (none)
• Enrollment: 33
• Locations: 25
• Arm: 1
• Duration (Months): 29
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Keppra injection is approved in the US as adjunctive therapy in the treatment of partial onset seizures in adults with epilepsy. The objective of the current study is to assess the safety, tolerability, and pharmacokinetics, of this formulation in children aged 4 to 16 years.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Levetiracetam	Phase 2

Detailed Description

The primary objective of this study was to evaluate the safety and tolerability of levetiracetam intravenous 15-minute infusion administered every 12 hours, either as adjunctive treatment or monotherapy in children (4 to 16 years old) with epilepsy (except status epilepticus), either after switching from the equivalent levetiracetam oral dose administration or as a new antiepileptic treatment.

The evaluation period was to be considered as one complete set of 4 Pharmacokinetic (PK) samples for a maximum of 4 days;

• For children already taking levetiracetam oral tablets or oral solution prior to entering the study, the levetiracetam intravenous (LEV IV) dose will be equivalent (mg-for-mg) to their oral dose. The first intravenous (IV) infusion was to be administered 12 hours after the last oral dose of levetiracetam.

• For children not taking levetiracetam oral tablets or oral solution prior to entering the study:

• If weight < 50 kg: dose of levetiracetam intravenous (LEV IV) dose will be calculated on the basis of their weight at 20 mg/kg/day (i.e. 10 mg/kg twice daily).

• If weight ≥ 50 kg: dose of levetiracetam intravenous (LEV IV) will be 1000 mg/day (i.e. 500 mg twice daily).

However, when necessary for the safety of the subject or when the investigator deemed it appropriate the levetiracetam intravenous (LEV IV) dose could be modified after one day.

Subjects were hospitalized for the duration of the levetiracetam IV treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Single-arm, Multi-center, Pharmacokinetic, Safety and Tolerability Study of Levetiracetam Intravenous Infusion in Children (4 - 16 Years Old) With Epilepsy.
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Levetiracetam

Drug: Levetiracetam; 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. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily).; Other Names: ucb L059 Keppra®

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Reporting at Least 1 Treatment-Emergent Adverse Event (TEAE) During the Treatment Period (up to 4 Days) [Treatment period (up to 4 days)]

Secondary Outcome Measures

1. Number of Subjects Who Received High-dose Levetiracetam Intravenous (LEV IV) (More Than 40 mg/kg/Day) During the Treatment Period (up to 4 Days) [Treatment period (up to 4 days)]

2. Number of Consecutive Levetiracetam Intravenous (LEV IV) Doses Received [Treatment period (up to 4 days)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female between 4 and 16 years of age, inclusive

• The subject suffers from epilepsy (except status epilepticus)

• The subject is requiring levetiracetam IV treatment in place of oral therapy for a short period of time

Exclusion Criteria:

• The subject has difficult venous accessibility

• History of status epilepticus during the 3 months prior to visit 1.

• The subject is taking felbamate at visit 1 or has been taking it in the past.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		La Jolla	California	United States
2		Boston	Massachusetts	United States
3		Chesterfield	Missouri	United States
4		Buffalo	New York	United States
5		Philadelphia	Pennsylvania	United States
6		Nashville	Tennessee	United States
7		Fort Worth	Texas	United States
8		Richmond	Virginia	United States
9		Milwaukee	Wisconsin	United States
10		Brussels		Belgium
11		Gent		Belgium
12		Leuven		Belgium
13		Amiens		France
14		Lille		France
15		Paris		France
16		Heidelberg		Germany
17		Kehl		Germany
18		Torreon	Coahuila	Mexico
19		Puebla	CP	Mexico
20		Aguascalientes		Mexico
21		Guadalajara		Mexico
22		Mexico City		Mexico
23		Puebla		Mexico
24		Ankara		Turkey
25		Izmir		Turkey

Sponsors and Collaborators

• UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] (UCB)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00535392
• Other Study ID Numbers: N01274; 2006-005722-23
• First Posted: Sep 26, 2007
• Last Update Posted: Aug 31, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by UCB Pharma: Epilepsy; Child; Levetiracetam; Keppra®; Infusion; Intravenous
• Additional relevant MeSH terms: Epilepsy; Levetiracetam

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from sites in the United States, Belgium, Germany, France, Mexico, and Turkey. The study began in September 2007 and continued until February 2010, with the last subject's visit occurring in February of 2010.

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. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily).
Period Title: Overall Study
STARTED	33
COMPLETED	33
NOT COMPLETED	0

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. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily).
Overall Participants	33
Age (Count of Participants)
<=18 years	33 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.71 (3.38)
Sex: Female, Male (Count of Participants)
Female	14 42.4%
Male	19 57.6%
Region of Enrollment (participants) [Number]
France	4 12.1%
United States	7 21.2%
Mexico	10 30.3%
Belgium	5 15.2%
Turkey	6 18.2%
Germany	1 3%

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)
Time Frame	Treatment period (up to 4 days)

Outcome Measure Data

Analysis Population Description

All 33 subjects enrolled in the study were 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. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily).
Measure Participants	33
Number [Subjects]	21

2. Secondary Outcome

Title	Number of Subjects Who Received High-dose Levetiracetam Intravenous (LEV IV) (More Than 40 mg/kg/Day) During the Treatment Period (up to 4 Days)
Time Frame	Treatment period (up to 4 days)

Outcome Measure Data

Analysis Population Description

All 33 subjects enrolled in the study were 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. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily).
Measure Participants	33
Number [Subjects]	10

3. Secondary Outcome

Title	Number of Consecutive Levetiracetam Intravenous (LEV IV) Doses Received
Time Frame	Treatment period (up to 4 days)

Outcome Measure Data

Analysis Population Description

All 33 subjects enrolled in the study were 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. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily).
Measure Participants	33
Mean (Standard Deviation) [Consecutive doses]	3.73 (1.61)

Adverse Events

Time Frame	Up to 4 days
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. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily).
All Cause Mortality
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	3/33 (9.1%)
Gastrointestinal disorders
VOMITING	1/33 (3%)	1
General disorders
PYREXIA	1/33 (3%)	1
Nervous system disorders
CONVULSION	1/33 (3%)	1
Other (Not Including Serious) Adverse Events
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	12/33 (36.4%)
Gastrointestinal disorders
NAUSEA	3/33 (9.1%)	3
DRY MOUTH	3/33 (9.1%)	3
VOMITING	2/33 (6.1%)	3
General disorders
PYREXIA	2/33 (6.1%)	3
Investigations
WEIGHT DECREASED	2/33 (6.1%)	2
Nervous system disorders
CONVULSION	3/33 (9.1%)	5
SOMNOLENCE	2/33 (6.1%)	7
Vascular disorders
HYPOTENSION	3/33 (9.1%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.