Open Label Safety and Efficacy Study of Levetiracetam in Patients With Epilepsy

• ClinicalTrials.gov Identifier: NCT00160654
• Recruitment Status: Completed
• First Posted: September 12, 2005
• Results First Posted: August 19, 2020
• Last Update Posted: August 19, 2020
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epilepsy, Partial
• Intervention: Drug: Levetiracetam
• Enrollment: 251

Participant Flow

Recruitment Details	The study started to enroll patients in November 2003 and concluded in May 2006.
Pre-assignment Details	Participant Flow refers to the Intend-to-treat (ITT) Set.

Arm/Group Title	Levetiracetam
Arm/Group Description	Subjects received open-label Levetiracetam.
Period Title: Overall Study
Started	251
Completed	218
Not Completed	33
Reason Not Completed
Adverse Event	14
Lack of Efficacy	4
Lost to Follow-up	2
Intake of expired drug	7
Psychological trauma	1
Sponsor decision	1
Patient met exclusion criteria	1
Patient decision	1
Poor compliance, dilantin toxicity	1
Met exclusion criteria	1

Baseline Characteristics

Arm/Group Title		Levetiracetam
Arm/Group Description		Subjects received open-label Levetiracetam.
Overall Number of Baseline Participants		251
Baseline Analysis Population Description		Baseline characteristics refer to the Intend-to-treat (ITT) Set.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	251 participants
	<=18 years	10 4.0%
	Between 18 and 65 years	240 95.6%
	>=65 years	1 0.4%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	251 participants
		34.42 (11.21)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	251 participants
	Female	137 54.6%
	Male	114 45.4%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Adverse Events (AEs)
Description	An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.
Time Frame	From Baseline until Safety visit (two weeks after last dose; up to Week 18)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levetiracetam
Arm/Group Description:	Subjects received open-label Levetiracetam.
Overall Number of Participants Analyzed	251
Measure Type: Number; Unit of Measure: Participants
	184

2. Secondary Outcome

Title	Percentage Change From Historical Baseline in Partial (Type I) Seizure Frequency Per Week Over the Treatment Period
Description	Percentage change from baseline in partial (Type I) seizure frequency over the treatment period standardized to 1 week period. Type I Partial (focal, local) seizure frequency per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period. A negative value in percent change from historical baseline indicates a decrease in partial (type I) seizure frequency from historical baseline.
Time Frame	Week 16, compared to Baseline

Outcome Measure Data

Analysis Population Description

Only subjects with partial (Type I) seizure frequency per week at baseline >= 0 and non-missing values on treatment period are included in the analysis.

Subjects withdrawing from the study are included up to their early discontinuation visit.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Subjects received open-label Levetiracetam.
Overall Number of Participants Analyzed	237
Median (Inter-Quartile Range); Unit of Measure: percentage changes
	-48.34; (-89.96 to 6.19)

3. Secondary Outcome

Title	Percentage Change From Historical Baseline in Total (Type I+II+III) Seizure Frequency Per Week Over the Treatment Period
Description	Percentage change from baseline in total (type I+II+III) seizure frequency over the treatment period standardized to 1 week period. Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or non-convulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period. A negative value in percent change from historical baseline indicates a decrease in total (type I+II+III) seizure frequency from historical baseline.
Time Frame	Week 16, compared to Baseline

Outcome Measure Data

Analysis Population Description

Only subjects with total (Type I+II+III) seizure frequency per week at baseline >= 0 and non-missing values on treatment period are included in the analysis.

Subjects withdrawing from the study are included up to their early discontinuation visit.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Subjects received open-label Levetiracetam.
Overall Number of Participants Analyzed	243
Median (Inter-Quartile Range); Unit of Measure: percentage changes
	-46.43; (-89.29 to 5.88)

4. Secondary Outcome

Title	Percentage of Participants With 50% Response in Seizure Frequency Per Week at Week 16
Description	50% response in seizure frequency per Week is defined as >=50% reduction in seizure frequency from Baseline. Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or non-convulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period.
Time Frame	Week 16, compared to Baseline

Outcome Measure Data

Analysis Population Description

Only subjects with seizure frequency per week at baseline >= 0 and non-missing values on treatment period are taken into account for the responder rates. By convention, subjects with frequency per week at baseline equal to zero were considered as non-responder.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Subjects received open-label Levetiracetam.
Overall Number of Participants Analyzed	243
Measure Type: Number; Unit of Measure: percentage of participants
Partial (Type I) seizures	47.7
Total (type I+II+III) seizures	48.1

5. Secondary Outcome

Title	Percentage of Participants With 100% Response in Seizure Frequency Per Week at Week 16
Description	100% response in seizure frequency per Week is defined as 100% reduction in seizure frequency from Baseline. Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or non-convulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 1 week period.
Time Frame	Week 16, compared to Baseline

Outcome Measure Data

Analysis Population Description

Only subjects with seizure frequency per week at baseline >= 0 and non-missing values on treatment period are taken into account for the responder rates. By convention, subjects with frequency per week at baseline equal to zero were considered as non-responder.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Subjects received open-label Levetiracetam.
Overall Number of Participants Analyzed	243
Measure Type: Number; Unit of Measure: percentage of participants
Partial (Type I) seizures	20.2
Total (type I+II+III) seizures	20.2

6. Secondary Outcome

Title	Percentage of Patients With Categorized Change From Baseline in Severity of Illness
Description	The overall change in the severity of the subject's illness, compared to the subject's condition prior to the levetiracetam intake, was assessed by the Investigator using Investigator's Global Evaluation Scale (IGS). Categories are as following: Marked improvement; Moderate improvement; Slight improvement; No change; Slight worsening; Moderate worsening; Marked worsening.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levetiracetam
Arm/Group Description:	Subjects received open-label Levetiracetam.
Overall Number of Participants Analyzed	251
Measure Type: Number; Unit of Measure: percentage of participants
Marked improvement	34.1
Moderate improvement	25.3
Slight improvement	16.5
No change	17.7
Slight worsening	3.2
Moderate worsening	2.8
Marked worsening	0.4

7. Secondary Outcome

Title	Retention Rate at Week 16
Description	Retention rate, defined as the number of subjects who were still on levetiracetam at Visit 5 (Week 16) or on the day before divided by the number of subjects in the ITT population.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levetiracetam
Arm/Group Description:	Subjects received open-label Levetiracetam.
Overall Number of Participants Analyzed	251
Measure Type: Number; Unit of Measure: percentage of participants
	85.3

Adverse Events

Time Frame	Adverse events were collected from Visit 2 (week 2) until Safety Visit (up to 2 weeks after the last dose, up to 16 weeks).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Levetiracetam
Arm/Group Description	Subjects received open-label Levetiracetam.
All-Cause Mortality
	Levetiracetam
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Levetiracetam
	Affected / at Risk (%)
Total	15/251 (5.98%)
Blood and lymphatic system disorders
Bicytopenia * 1	1/251 (0.40%)
General disorders
Adverse drug reaction * 1	1/251 (0.40%)
Infections and infestations
Dengue fever * 1	1/251 (0.40%)
Injury, poisoning and procedural complications
Thermal burn * 1	1/251 (0.40%)
Nervous system disorders
Convulsion * 1	4/251 (1.59%)
Coordination abnormal * 1	1/251 (0.40%)
Depressed level of consciousness * 1	1/251 (0.40%)
Dizziness * 1	2/251 (0.80%)
Grand mal convulsion * 1	2/251 (0.80%)
Lethargy * 1	1/251 (0.40%)
Somnolence * 1	1/251 (0.40%)
Psychiatric disorders
Aggression * 1	1/251 (0.40%)
Anger * 1	1/251 (0.40%)
Hallucination, auditory * 1	1/251 (0.40%)
Suicide attempt * 1	1/251 (0.40%)
Skin and subcutaneous tissue disorders
Rash * 1	1/251 (0.40%)
Rash maculo-papular * 1	1/251 (0.40%)
Stevens-Johnson syndrome * 1	1/251 (0.40%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Levetiracetam
	Affected / at Risk (%)
Total	136/251 (54.18%)
Gastrointestinal disorders
Nausea * 1	14/251 (5.58%)
General disorders
Fatigue * 1	15/251 (5.98%)
Nervous system disorders
Dizziness * 1	36/251 (14.34%)
Headache * 1	16/251 (6.37%)
Sedation * 1	15/251 (5.98%)
Somnolence * 1	75/251 (29.88%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA

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.

Results Point of Contact

• Name/Title: UCB
• Organization: Cares
• Phone: +1844 599 ext 2273
• EMail: UCBCares@ucb.com

Publications of Results:

Kwan P, Lim SH, Chinvarun Y, Cabral-Lim L, Aziz ZA, Lo YK, Tonner F, Beh K, Edrich P; N01036 (SKATE II) Investigator Group. Efficacy and safety of levetiracetam as adjunctive therapy in adult patients with uncontrolled partial epilepsy: the Asia SKATE II Study. Epilepsy Behav. 2010 May;18(1-2):100-5. doi: 10.1016/j.yebeh.2010.03.016. Epub 2010 May 11.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00160654
• Other Study ID Numbers: N01036
• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Results First Submitted: February 8, 2018
• Results First Posted: August 19, 2020
• Last Update Posted: August 19, 2020