Conversion to Monotherapy Study With Keppra XR for Partial Seizures

• ClinicalTrials.gov Identifier: NCT00419094
• Recruitment Status: Completed
• First Posted: January 8, 2007
• Results First Posted: December 20, 2010
• Last Update Posted: September 5, 2014
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Epilepsy
• Intervention: Drug: Keppra XR
• Enrollment: 228

Participant Flow

Recruitment Details	The Efficacy (EFF) population is defined as all subjects in the Intent to Treat (ITT) population who enter into the Previous Antiepileptic (AED) Discontinuation (D/C) Phase. The Per Protocol (PP) population consists of all subjects in the EFF population who have no important protocol deviations related to efficacy.
Pre-assignment Details	Subjects are to be randomized into treatment with either Keppra XR 2000 mg/day or Keppra XR 1000 mg/day in a 3:1 ratio.

Arm/Group Title	Keppra XR 1000 mg/Day	Keppra XR 2000 mg/Day
Arm/Group Description	1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)	2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
Period Title: Overall Study
Started	57 [1]	171
Completed	50	141
Not Completed	7	30
Reason Not Completed
Adverse Event	3	7
Lack of Efficacy	1	0
Lost to Follow-up	0	2
Protocol Violation	1	14
Withdrawal of consent	1	5
Other: Error determining exit criteria	1	0
Other: Patient non-compliant	0	1
Other: No contact for extended period	0	1
[1] Number started refers to number randomized; 303 subjects were screened/enrolled and 228 randomized.

Baseline Characteristics

Arm/Group Title		Keppra XR 1000 mg/Day	Keppra XR 2000 mg/Day	Total
Arm/Group Description		1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)	2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)	Total of all reporting groups
Overall Number of Baseline Participants		57	171	228
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	57 participants	171 participants	228 participants
	<=18 years	11 19.3%	31 18.1%	42 18.4%
	Between 18 and 65 years	43 75.4%	140 81.9%	183 80.3%
	>=65 years	3 5.3%	0 0.0%	3 1.3%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	57 participants	171 participants	228 participants
		33.48 (16.32)	34.31 (13.69)	34.11 (14.36)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	57 participants	171 participants	228 participants
	Female	33 57.9%	99 57.9%	132 57.9%
	Male	24 42.1%	72 42.1%	96 42.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	57 participants	171 participants	228 participants
United States		8	29	37
Mexico		17	43	60
Poland		16	51	67
Russian Federation		16	48	64

Outcome Measures

1. Primary Outcome

Title	The Cumulative Exit Rate at 112 Days After the Beginning of the Previous Antiepileptic Drug (AED) Tapering Phase
Description	Cumulative exit rate at day 112, based on the duration between start date of previous AED tapering to the earliest date exit criterion was met; calculated using Kaplan Meier Methods. Subjects prematurely discontinued for reasons unrelated to exit criteria were censored as of last dose of study drug. Subjects who completed without meeting exit criteria were censored at Day 112. Exit criteria include increase in seizure frequency, severity, duration, status epilepticus, or new generalized seizure. Upper 95% 2-sided confidence limit for exit rate is compared to the historical control rate: 0.678.
Time Frame	112 days

Outcome Measure Data

Analysis Population Description

Of the 171 (Keppra 2000 mg) subjects randomized, 158 subjects entered the Previous Antiepileptic Drug Tapering Phase and were included in the Efficacy Population. Primary Efficacy analysis was conducted for the Keppra XR 2000 mg/day group only.

Arm/Group Title	Keppra XR 1000 mg/Day	Keppra XR 2000 mg/Day
Arm/Group Description:	1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)	2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
Overall Number of Participants Analyzed	0	158
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of subjects
		0.375; (0.297 to 0.453)

2. Secondary Outcome

Title	The Cumulative Rate of Exit Events, Which Include Discontinuation Due to Exit Criteria, Withdrawal Due to Adverse Events (AE) and Withdrawal Due to Lack of Efficacy, at 112 Days After the Beginning of Previous Antiepileptic Drug (AED) Tapering Phase
Description	The cumulative exit event rate at Day 112 was calculated using Kaplan Meier methods. The exit event rate estimate was based on the duration between the start date of previous AED tapering to the earliest date an exit event occured. Subjects who prematurely discontinued for reasons unrelated to exit criteria, adverse event, or lack of efficacy were censored as of the last dose of study medication. Subjects who completed the study without having an exit event were censored as of Day 112.
Time Frame	112 days

Outcome Measure Data

Analysis Population Description

Of the 171 (Keppra 2000 mg) subjects randomized, 158 subjects entered the Previous Antiepileptic Drug Tapering Phase and were included in the Efficacy Population. Evaluated for Keppra XR 2000 mg/day only.

Arm/Group Title	Keppra XR 1000 mg/Day	Keppra XR 2000 mg/Day
Arm/Group Description:	1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)	2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
Overall Number of Participants Analyzed	0	158
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of subjects
		0.385; (0.307 to 0.463)

3. Secondary Outcome

Title	The Cumulative Rate of Exit Events Due to Any Reasons at 112 Days After the Beginning of Previous Antiepileptic Drug (AED) Tapering Phase
Description	The cumulative exit event rate at Day 112 was calculated using Kaplan Meier methods. The exit event rate estimate was based on the duration between the start date of previous AED tapering to the earliest date an exit event occured. Subjects who completed the study without having an exit event were censored as of Day 112.
Time Frame	112 days

Outcome Measure Data

Analysis Population Description

Of the 171 (Keppra 2000 mg) subjects randomized, 158 subjects entered the Previous Antiepileptic Drug Tapering Phase and were included in the Efficacy Population. Evaluated for Keppra XR 2000 mg/day only.

Arm/Group Title	Keppra XR 1000 mg/Day	Keppra XR 2000 mg/Day
Arm/Group Description:	1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)	2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
Overall Number of Participants Analyzed	0	158
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of subjects
		0.475; (0.397 to 0.553)

4. Secondary Outcome

Title	The Cumulative Exit Rate at 112 Days for the Keppra XR 1000 mg Group After the Beginning of the Previous Antiepileptic Drug (AED) Tapering Phase
Description	Keppra XR 1000 mg arm was not intended for inferential analysis (planned 3 to 1 randomization, Keppra XR 2000 mg: 1000 mg). The Exit Rate was based on the duration between the start date of previous AED tapering to the earliest date an exit crterion was met. Subjects who prematurely discontinued for reasons unrelated to exit criteria were censored as of the last dose of study medication. Subjects who completed the study without meeting an exit criterion were censored as of Day 112.
Time Frame	112 days

Outcome Measure Data

Analysis Population Description

Of the 57 (Keppra 1000 mg) subjects randomized, 54 subjects entered the Previous Antiepileptic Drug Tapering Phase and were included in the Efficacy Population.

Arm/Group Title	Keppra XR 1000 mg/Day	Keppra XR 2000 mg/Day
Arm/Group Description:	1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)	2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
Overall Number of Participants Analyzed	54	0
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of subjects
	0.334; (0.204 to 0.465)

Adverse Events

Time Frame	Up to 29 weeks
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Keppra XR 1000 mg/Day		Keppra XR 2000 mg/Day
Arm/Group Description	1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)		2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
All-Cause Mortality
	Keppra XR 1000 mg/Day		Keppra XR 2000 mg/Day
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Keppra XR 1000 mg/Day		Keppra XR 2000 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/57 (3.51%)		12/171 (7.02%)
Gastrointestinal disorders
haemorrhoidal haemorrhage * 1	0/57 (0.00%)	0	1/171 (0.58%)	1
pancreatitis acute * 1	0/57 (0.00%)	0	1/171 (0.58%)	1
Infections and infestations
pulmonary tuberculosis * 1	0/57 (0.00%)	0	1/171 (0.58%)	1
pyelonephritis * 1	0/57 (0.00%)	0	1/171 (0.58%)	1
Injury, poisoning and procedural complications
ankle fracture * 1	0/57 (0.00%)	0	1/171 (0.58%)	1
Musculoskeletal and connective tissue disorders
back pain * 1	0/57 (0.00%)	0	1/171 (0.58%)	1
intervertebral disc protrusion * 1	0/57 (0.00%)	0	1/171 (0.58%)	1
lumbar spinal stenosis * 1	0/57 (0.00%)	0	1/171 (0.58%)	1
Nervous system disorders
convulsion * 1	1/57 (1.75%)	1	4/171 (2.34%)	4
status epilepticus * 1	0/57 (0.00%)	0	1/171 (0.58%)	1
Psychiatric disorders
acute psychosis * 1	1/57 (1.75%)	1	0/171 (0.00%)	0
Vascular disorders
thrombosis * 1	0/57 (0.00%)	0	1/171 (0.58%)	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%
	Keppra XR 1000 mg/Day		Keppra XR 2000 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/57 (57.89%)		87/171 (50.88%)
Ear and labyrinth disorders
vertigo * 1	3/57 (5.26%)	3	7/171 (4.09%)	7
Gastrointestinal disorders
abdominal pain * 1	3/57 (5.26%)	3	6/171 (3.51%)	6
General disorders
irritablility * 1	3/57 (5.26%)	3	12/171 (7.02%)	12
Infections and infestations
nasopharyngitis * 1	3/57 (5.26%)	3	7/171 (4.09%)	7
Nervous system disorders
somnolence * 1	12/57 (21.05%)	13	38/171 (22.22%)	40
headache * 1	13/57 (22.81%)	34	32/171 (18.71%)	55
convulsion * 1	9/57 (15.79%)	9	20/171 (11.70%)	20
dizziness * 1	3/57 (5.26%)	4	15/171 (8.77%)	19
* 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: Study Director
• Organization: UCB, Inc.
• Phone: +1 877 822 9493

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chung S, Ceja H, Gawlowicz J, Avakyan G, McShea C, Schiemann J, Lu S. Levetiracetam extended release conversion to monotherapy for the treatment of patients with partial-onset seizures: a double-blind, randomised, multicentre, historical control study. Epilepsy Res. 2012 Aug;101(1-2):92-102. doi: 10.1016/j.eplepsyres.2012.03.007. Epub 2012 Apr 18.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00419094
• Other Study ID Numbers: N01280; 2007-000897-21 ( EudraCT Number )
• First Submitted: January 4, 2007
• First Posted: January 8, 2007
• Results First Submitted: September 13, 2010
• Results First Posted: December 20, 2010
• Last Update Posted: September 5, 2014