A Long Term Follow up Administration Study of L059 (Levetiracetam) in Epilepsy Patients With Partial Onset Seizures

• ClinicalTrials.gov Identifier: NCT00367432
• Recruitment Status: Completed
• First Posted: August 22, 2006
• Results First Posted: January 16, 2012
• Last Update Posted: November 13, 2020
• Sponsor: UCB Japan Co. Ltd.
• Information provided by (Responsible Party): UCB Pharma ( UCB Japan Co. Ltd. )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Epilepsies; Partial
• Intervention: Drug: Levetiracetam
• Enrollment: 398

Participant Flow

Recruitment Details	The Full Analysis Set (FAS) includes all subjects to whom the investigational products are assigned after registration, excluding those with serious Good Clinical Practice violations , subjects not administered the investigational products and subjects for whom no data is available after assignment of the investigational products.
Pre-assignment Details	Eligible subjects from preceding study N01221 [NCT00280696] entered the First Period of this study and those subjects from N01221 [NCT00280696] who completed the First Period and subjects from the study N01020 [NCT00160615] entered the Second Period. Participant Flow and Baseline Characteristics refer to the FAS.

Arm/Group Title	Levetiracetam N01221 [NCT00280696]	Levetiracetam N01020 [NCT00160615]
Arm/Group Description	N01221 [NCT00280696] was a double-blind, randomized, multicenter, placebo controlled 5 parallel groups, confirmatory trial to evaluate the efficacy and safety of Levetiracetam.	N01020 [NCT00160615] was an open-label follow-up study to evaluate safety and efficacy of Levetiracetam.
Period Title: First Period (16 Weeks)
Started	313 [1]	0
Completed	275	0
Not Completed	38	0
Reason Not Completed
Adverse Event	6	0
Lack of Efficacy	24	0
Withdrawal by Subject	6	0
Other Reason	2	0
[1] Eligible subjects from preceding study N01221 [NCT00280696] entered the First Period of N01222
Period Title: Second Period (up to 54 Months)
Started	275 [1]	85 [2]
Completed	188	69
Not Completed	87	16
Reason Not Completed
Adverse Event	14	3
Lack of Efficacy	59	5
Lost to Follow-up	0	1
Withdrawal by Subject	8	5
Other Reason	6	2
[1] 275 subjects from N01221 [NCT00280696] completed First Period and entered Second Period of N01222; [2] 85 subjects from N01020 [NCT00160615] entered Second Period of N01222

Baseline Characteristics

Arm/Group Title		Levetiracetam
Arm/Group Description		Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Baseline Participants		398
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	398 participants
		33.68 (11.18)
Age, Customized; Measure Type: Number; Unit of measure: Participants
Between 16 and 65 years	Number Analyzed	398 participants
		398
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	398 participants
	Female	196 49.2%
	Male	202 50.8%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	398 participants
Japanese		396
Asian (other than Japanese)		2
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Japan	Number Analyzed	398 participants
		398
Weight; Mean (Standard Deviation); Unit of measure: Kilogram (kg)
	Number Analyzed	398 participants
		60.39 (13.64)

Outcome Measures

1. Primary Outcome

Title	Occurrence of Treatment-emergent Adverse Events During the Study Period (Until the Time of Approval Granted)
Description	An Adverse Event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with the pharmaceutical product. Occurrence of treatment-emergent AEs is reported by the number of subjects with at least one treatment-emergent AE.
Time Frame	During the study period from Visit 1 (Week 0) to the Follow-up Visit (up to Month 60) until the time of approval granted

Outcome Measure Data

Analysis Population Description

Safety Set includes all subjects from N01221 [NCT00280696] and N01020 [NCT00160615] administered the investigational products at least once.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Participants Analyzed	398
Measure Type: Number; Unit of Measure: participants
	381

2. Secondary Outcome

Title	Change From Baseline in N01221 [NCT00280696] in Partial (Type 1) Seizure Frequency Per Week During the First 16-week Period in This Study
Description	The change in partial (type 1) seizure frequency from Baseline is given as a percent reduction computed as: [ Weekly partial seizure frequency (Baseline)- Weekly partial seizure frequency (Evaluation Period)]/ [Weekly partial seizure frequency (Baseline)] x 100. Positive values in percent reduction means that the value has decreased from Baseline during the first 16-week Period. Partial (Type I) seizures can be classified into one of the following three groups: Simple partial seizures, Complex partial seizures, Partial seizures evolving to secondarily generalized seizures.
Time Frame	Baseline in N01221 [NCT00280696], the First 16-week Evaluation Period from Visit 1 (Week 0) to Visit 5 (Week 16) in this study

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Levetiracetam
Arm/Group Description:	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Participants Analyzed	313
Median (Inter-Quartile Range); Unit of Measure: Percent Reduction
	22.00; (-11.00 to 46.71)

3. Secondary Outcome

Title	Seizure Frequency Per Week in Partial Seizures During the First 16-week Period in This Study
Description	Partial (Type I) seizures can be classified into one of the following three groups: Simple partial seizures, Complex partial seizures, Partial seizures evolving to secondarily generalized seizures.
Time Frame	First 16-week Evaluation Period from Visit 1 (Week 0) to Visit 5 ( Week 16)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Levetiracetam
Arm/Group Description:	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Participants Analyzed	313
Median (Inter-Quartile Range); Unit of Measure: Seizures Per Week
	2.13; (1.06 to 5.23)

4. Secondary Outcome

Title	Response Status (Patients With a Percent Reduction in Partial Seizure Frequency of at Least 50% During the First 16-week Period in This Study From Baseline in N01221)
Description	The percent reduction from Baseline was computed as: [ Weekly seizure frequency (Baseline)- Weekly seizure frequency (Evaluation Period)]/ [Weekly seizure frequency (Baseline)] x 100. Responders are those patients with a percent reduction in partial seizure frequency of at least 50% from Baseline to first Evaluation Period in partial seizure frequency per week. Partial (Type I) seizures can be classified into one of the following three groups: Simple partial seizures, Complex partial seizures, Partial seizures evolving to secondarily generalized seizures.
Time Frame	Baseline in N01221 [NCT00280696], the First 16-week Evaluation Period from Visit 1 (Week 0) to Visit 5 (Week 16) in this study

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	Levetiracetam
Arm/Group Description:	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Participants Analyzed	313
Measure Type: Number; Unit of Measure: Participants
Responders	74
Non-responders	239

5. Secondary Outcome

Title	Change From Baseline in N01221 [NCT00280696] in Simple Partial Seizure Frequency Per Week During the First 16-week Period in This Study
Description	Change in simple partial seizure frequency is given as a percent reduction computed as: [ Weekly simple partial seizure frequency (Baseline)- Weekly simple partial seizure frequency (Evaluation Period)]/ [Weekly simple partial seizure frequency (Baseline)] x 100. Positive values in percent reduction means that the value has decreased from Baseline during the first 16-week Period. Partial (Type I) seizures can be classified into one of the following three groups: Simple partial seizures, Complex partial seizures, Partial seizures evolving to secondarily generalized seizures.
Time Frame	Baseline in N01221 [NCT00280696], the First 16-week Evaluation Period from Visit 1 (Week 0) to Visit 5 (Week 16) in this study

Outcome Measure Data

Analysis Population Description

Subset of the FAS population excluding subjects with seizure counts equal to zero during Baseline and Evaluation Period for Simple Partial Seizures.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Participants Analyzed	173
Median (Inter-Quartile Range); Unit of Measure: Percent Reduction
	39.84; (-17.19 to 94.96)

6. Secondary Outcome

Title	Change From Baseline in N01221 [NCT00280696] in Complex Partial Seizure Frequency Per Week During the First 16-week Period in This Study
Description	Change in complex partial seizure frequency is given as a percent reduction computed as: [ Weekly complex partial seizure frequency (Baseline)- Weekly complex partial seizure frequency (Evaluation Period)]/ [Weekly complex partial seizure frequency (Baseline)] x 100. Positive values in percent reduction means that the value has decreased from Baseline during the first 16-week Period. Partial (Type I) seizures can be classified into one of the following three groups: Simple partial seizures, Complex partial seizures, Partial seizures evolving to secondarily generalized seizures.
Time Frame	Baseline in N01221 [NCT00280696], the First 16-week Evaluation Period from Visit 1 (Week 0) to Visit 5 (Week 16) in this study

Outcome Measure Data

Analysis Population Description

Subset of the FAS population excluding subjects with seizure counts equal to zero during Baseline and Evaluation Period for Complex Partial Seizures.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Participants Analyzed	285
Median (Inter-Quartile Range); Unit of Measure: Percent Reduction
	20.59; (-15.24 to 52.94)

7. Secondary Outcome

Title	Change From Baseline in N01221 [NCT00280696] in Secondary Generalized Seizure Frequency Per Week During the First 16-week Period in This Study
Description	Change in secondary generalized seizure frequency is given as a percent reduction computed as: [ Weekly sec. generalized seizure frequency (Baseline)- Weekly sec. generalized seizure frequency (Evaluation Period)]/ [Weekly sec. generalized seizure frequency (Baseline)] x 100. Positive values in reduction means the value decreased from Baseline during the first 16-week Period. Secondary generalized seizures belong to one of the 3 groups: Simple partial sz evolving to gen sz; Complex partial sz evolving to gen sz; Simple partial sz evolving to Complex partial sz evolving to gen sz
Time Frame	Baseline in N01221 [NCT00280696], the First 16-week Evaluation Period from Visit 1 (Week 0) to Visit 5 (Week 16) in this study

Outcome Measure Data

Analysis Population Description

Subset of the FAS population excluding subjects with seizure counts equal to zero during Baseline and Evaluation Period for Secondary Generalized Seizures.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Participants Analyzed	87
Median (Inter-Quartile Range); Unit of Measure: Percent Reduction
	76.56; (23.11 to 100.00)

8. Secondary Outcome

Title	Change From Baseline in N01221 [NCT00280696] in Simple and Complex Partial Seizure Frequency Per Week During the First 16-week Period in This Study
Description	Change in simple and complex partial seizure frequency is given as a percent reduction computed as (simple and complex partial seizure frequency := A): [ Weekly A (Baseline)- Weekly A (Evaluation Period)]/ [Weekly A (Baseline)] x 100. Positive values in percent reduction means that the value has decreased from Baseline during the first 16-week Period. Partial (Type I) seizures can be classified into one of the following three groups: Simple partial seizures, Complex partial seizures, Partial seizures evolving to secondarily generalized seizures.
Time Frame	Baseline in N01221 [NCT00280696], the First 16-week Evaluation Period from Visit 1 (Week 0) to Visit 5 (Week 16) in this study

Outcome Measure Data

Analysis Population Description

Subset of the FAS population excluding subjects with seizure counts equal to zero during Baseline and Evaluation Period for Simple and Complex Partial Seizures.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Participants Analyzed	308
Median (Inter-Quartile Range); Unit of Measure: Percent Reduction
	20.71; (-13.17 to 47.42)

9. Secondary Outcome

Title	Change From Baseline in N01221 [NCT00280696] in Other Types of Seizure Frequency Per Week During the First 16-week Period in This Study
Description	Change in other types of seizure frequency is given as a percent reduction computed as (other types of seizure frequency:= B): [ Weekly B (Baseline)- Weekly B (Evaluation Period)]/ [Weekly B (Baseline)] x 100. Positive values in percent reduction means that the value has decreased from Baseline during the first 16-week Period. Other types of Seizures are all seizures except Partial Seizures (Type 1).
Time Frame	Baseline in N01221 [NCT00280696], the First 16-week Evaluation Period from Visit 1 (Week 0) to Visit 5 (Week 16) in this study

Outcome Measure Data

Analysis Population Description

Subset of the FAS population excluding subjects with seizure counts equal to zero during Baseline and Evaluation Period for Other Types of Seizures.

Arm/Group Title	Levetiracetam
Arm/Group Description:	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
Overall Number of Participants Analyzed	5
Median (Inter-Quartile Range); Unit of Measure: Percent Reduction
	66.47; (7.48 to 100.00)

Adverse Events

Time Frame	Adverse Events (AEs) were collected up to 60 months from Visit 1 (Week 0) over the First and Second Period until Down-titration and Follow up.
Adverse Event Reporting Description	Adverse Events refer to the Safety Set (SS). SS includes all subjects from studies N01221 [NCT00280696] and N01020 [NCT00160615] administered the investigational products at least once.
Arm/Group Title	Levetiracetam
Arm/Group Description	Levetiracetam 500 mg/day to 3000 mg/day , tablets twice daily (morning and evening orally) during the study period (until the time of approval granted).
All-Cause Mortality
	Levetiracetam
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Levetiracetam
	Affected / at Risk (%)	# Events
Total	64/398 (16.08%)
Blood and lymphatic system disorders
Anaemia * 1	1/398 (0.25%)	1
Cardiac disorders
Palpitations * 1	1/398 (0.25%)	1
Eye disorders
Eyelid Ptosis * 1	1/398 (0.25%)	1
Gastrointestinal disorders
Enterocolitis * 1	1/398 (0.25%)	1
Ileus * 1	1/398 (0.25%)	1
Intestinal Obstruction * 1	1/398 (0.25%)	1
Irritable Bowel Syndrome * 1	1/398 (0.25%)	1
Rectal Ulcer Haemorrhage * 1	1/398 (0.25%)	1
Colonic Polyp * 1	1/398 (0.25%)	1
General disorders
Pain * 1	1/398 (0.25%)	1
Pyrexia * 1	2/398 (0.50%)	2
Sudden Unexplained Death in Epilepsy * 1	1/398 (0.25%)	1
Immune system disorders
Drug Hypersensitivity * 1	1/398 (0.25%)	1
Infections and infestations
Acute Sinusitis * 1	1/398 (0.25%)	1
Cellulitis * 1	1/398 (0.25%)	1
Gastroenteritis Escherichia Coli * 1	1/398 (0.25%)	1
Infected Epidermal Cyst * 1	1/398 (0.25%)	1
Injection Site Infection * 1	1/398 (0.25%)	1
Lobar Pneumonia * 1	1/398 (0.25%)	1
Pneumonia * 1	4/398 (1.01%)	4
Pneumonia Mycoplasmal * 1	1/398 (0.25%)	1
Pyelonephritis * 1	1/398 (0.25%)	1
Respiratory Tract Infection * 1	1/398 (0.25%)	1
Sepsis * 1	1/398 (0.25%)	1
Injury, poisoning and procedural complications
Anticonvulsant Toxicity * 1	3/398 (0.75%)	3
Burns Second Degree * 1	1/398 (0.25%)	1
Cervical Vertebral Fracture * 1	1/398 (0.25%)	1
Femoral Neck Fracture * 1	1/398 (0.25%)	1
Head Injury * 1	1/398 (0.25%)	1
Lumbar Vertebral Fracture * 1	1/398 (0.25%)	1
Patella Fracture * 1	1/398 (0.25%)	1
Rib Fracture * 1	1/398 (0.25%)	1
Road Traffic Accident * 1	1/398 (0.25%)	1
Skin Laceration * 1	3/398 (0.75%)	3
Skull Fracture * 1	1/398 (0.25%)	1
Subdural Haematoma * 1	1/398 (0.25%)	1
Investigations
Anticonvulsant Drug Level Increased * 1	2/398 (0.50%)	2
Electrocardiogram ST Segment Elevation * 1	1/398 (0.25%)	1
Musculoskeletal and connective tissue disorders
Haemarthrosis * 1	1/398 (0.25%)	1
Jaw Disorder * 1	1/398 (0.25%)	1
Spinal Column Stenosis * 1	1/398 (0.25%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma * 1	1/398 (0.25%)	1
Small Intestine Carcinoma * 1	1/398 (0.25%)	1
Nervous system disorders
Cerebral Infarction * 1	1/398 (0.25%)	1
Complex Partial Seizures * 1	1/398 (0.25%)	1
Convulsion * 1	1/398 (0.25%)	1
Dizziness * 1	1/398 (0.25%)	1
Drug Withdrawal Convulsions * 1	1/398 (0.25%)	1
Epilepsy * 1	5/398 (1.26%)	5
Head Titubation * 1	1/398 (0.25%)	1
Neuropathy Peripheral * 1	1/398 (0.25%)	1
Postictal State * 1	1/398 (0.25%)	1
Status Epilepticus * 1	5/398 (1.26%)	9
Pregnancy, puerperium and perinatal conditions
Abortion Complete * 1	1/398 (0.25%)	1
Psychiatric disorders
Acute Psychosis * 1	1/398 (0.25%)	1
Depression * 1	1/398 (0.25%)	1
Hallucination * 1	1/398 (0.25%)	1
Ideas of Reference * 1	1/398 (0.25%)	1
Mental Disorder * 1	1/398 (0.25%)	1
Morose * 1	1/398 (0.25%)	3
Suicide Attempt * 1	1/398 (0.25%)	1
Renal and urinary disorders
Urethral Stenosis * 1	1/398 (0.25%)	2
Reproductive system and breast disorders
Lactation Disorder * 1	1/398 (0.25%)	1
Respiratory, thoracic and mediastinal disorders
Atelectasis * 1	1/398 (0.25%)	1
Choking * 1	1/398 (0.25%)	1
Pneumonia Aspiration * 1	1/398 (0.25%)	1
Surgical and medical procedures
Abortion Induced * 1	2/398 (0.50%)	2
Brain Operation * 1	1/398 (0.25%)	1
Medical Diet * 1	1/398 (0.25%)	1
Wisdom Teeth Removal * 1	1/398 (0.25%)	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	369/398 (92.71%)
Gastrointestinal disorders
Abdominal Pain * 1	38/398 (9.55%)	67
Abdominal Pain Upper * 1	20/398 (5.03%)	40
Constipation * 1	45/398 (11.31%)	70
Diarrhoea * 1	69/398 (17.34%)	128
Nausea * 1	44/398 (11.06%)	53
Stomatitis * 1	42/398 (10.55%)	75
Toothache * 1	21/398 (5.28%)	32
Vomiting * 1	40/398 (10.05%)	85
General disorders
Pyrexia * 1	52/398 (13.07%)	95
Immune system disorders
Seasonal Allergy * 1	29/398 (7.29%)	43
Infections and infestations
Dental Caries * 1	42/398 (10.55%)	49
Gastroenteritis * 1	27/398 (6.78%)	34
Influenza * 1	32/398 (8.04%)	32
Nasopharyngitis * 1	308/398 (77.39%)	1360
Pharyngitis * 1	25/398 (6.28%)	38
Rhinitis * 1	22/398 (5.53%)	26
Injury, poisoning and procedural complications
Contusion * 1	110/398 (27.64%)	237
Excoriation * 1	52/398 (13.07%)	85
Injury * 1	33/398 (8.29%)	39
Joint Sprain * 1	27/398 (6.78%)	37
Laceration * 1	20/398 (5.03%)	23
Skin Laceration * 1	31/398 (7.79%)	53
Thermal Burn * 1	36/398 (9.05%)	43
Investigations
Weight Decreased * 1	28/398 (7.04%)	33
Musculoskeletal and connective tissue disorders
Arthralgia * 1	31/398 (7.79%)	34
Back Pain * 1	45/398 (11.31%)	70
Myalgia * 1	21/398 (5.28%)	27
Nervous system disorders
Dizziness * 1	63/398 (15.83%)	92
Epilepsy * 1	31/398 (7.79%)	37
Headache * 1	96/398 (24.12%)	261
Somnolence * 1	159/398 (39.95%)	226
Psychiatric disorders
Insomnia * 1	24/398 (6.03%)	26
Respiratory, thoracic and mediastinal disorders
Cough * 1	21/398 (5.28%)	25
Pharyngolaryngeal Pain * 1	32/398 (8.04%)	60
Rhinitis Allergic * 1	20/398 (5.03%)	26
Upper Respiratory Tract Inflammation * 1	33/398 (8.29%)	46
Skin and subcutaneous tissue disorders
Eczema * 1	47/398 (11.81%)	61
Pruritus * 1	21/398 (5.28%)	25
Rash * 1	26/398 (6.53%)	37
* 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.

Results Point of Contact

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

• Responsible Party: UCB Pharma ( UCB Japan Co. Ltd. )
• ClinicalTrials.gov Identifier: NCT00367432
• Other Study ID Numbers: N01222; 2014-004334-26 ( EudraCT Number )
• First Submitted: August 21, 2006
• First Posted: August 22, 2006
• Results First Submitted: December 2, 2011
• Results First Posted: January 16, 2012
• Last Update Posted: November 13, 2020