eValuation of the Efficacy and toleRability of Vimpat When Added to lEvetiracetam (VERVE)

• ClinicalTrials.gov Identifier: NCT01484977
• Recruitment Status: Completed
• First Posted: December 5, 2011
• Results First Posted: November 26, 2014
• Last Update Posted: July 18, 2018
• 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
• Intervention: Drug: Lacosamide
• Enrollment: 120

Participant Flow

Recruitment Details	The recruitment for the SP0980 study began in December 2011. It concluded in January 2014. This was a multicenter study with subjects enrolled by 30 sites across North America, 12 in Western Europe, 10 in Eastern Europe, and 2 in Oceania.
Pre-assignment Details	The participant flow consists of subjects in the Safety Set (SS). The SS is all subjects who received at least 1 dose of lacosamide.

Arm/Group Title	Lacosamide
Arm/Group Description	Lacosamide will be added to levetiracetam while withdrawing the sodium channel blocking antiepileptic drug (AED). Lacosamide: 50 mg and 100 mg lacosamide tablets will be combined and taken in two equal doses per day to provide the required total daily dosage of 100 - 600 mg/day. Subjects were titrated to a minimum of 200 mg/ day during the Treatment Period. Maximum duration of study drug administration is approximately 23 weeks.
Period Title: Overall Study
Started	120
Completed	93
Not Completed	27
Reason Not Completed
Adverse Event	8
Lack of Efficacy	4
Protocol Violation	6
Lost to Follow-up	1
Withdrawal by Subject	4
Subject Protocol Non-compliant	1
Moving Overseas	1
Low White Blood Cell Count	1
Lack of Compliance	1

Baseline Characteristics

Arm/Group Title		Lacosamide
Arm/Group Description		Lacosamide will be added to levetiracetam while withdrawing the sodium channel blocking antiepileptic drug (AED). Lacosamide: 50 mg and 100 mg lacosamide tablets will be combined and taken in two equal doses per day to provide the required total daily dosage of 100 - 600 mg/day. Subjects were titrated to a minimum of 200 mg/ day during the Treatment Period. Maximum duration of study drug administration is approximately 23 weeks.
Overall Number of Baseline Participants		120
Baseline Analysis Population Description		The Baseline characteristics consist of subjects in the Safety Set (SS). The SS is all subjects who received at least 1 dose of lacosamide.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	120 participants
	<=18 years	1 0.8%
	Between 18 and 65 years	114 95.0%
	>=65 years	5 4.2%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	120 participants
		39.7 (12.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	120 participants
	Female	74 61.7%
	Male	46 38.3%
Weight; Mean (Standard Deviation); Unit of measure: Kilograms
	Number Analyzed	120 participants
		76.39 (19.98)
Height; Mean (Standard Deviation); Unit of measure: Centimeters
	Number Analyzed	120 participants
		168.02 (10.55)
BMI; Mean (Standard Deviation); Unit of measure: Kilogram/ square meter
	Number Analyzed	120 participants
		27.00 (6.45)
Racial Group; Measure Type: Number; Unit of measure: Participants	Number Analyzed	120 participants
American Indian/Alaskan Native		1
Asian		3
Black		8
Native Hawaiian or other Pacific Islander		0
White		96
Other/Mixed		12
Ethnicity; Measure Type: Number; Unit of measure: Participants	Number Analyzed	120 participants
Hispanic or Latino		17
Not Hispanic or Latino		103

Outcome Measures

1. Primary Outcome

Title	Retention at the End of the 21-week Treatment Period
Description	Retention is a summary measure that integrates both the patient's and clinician's assessment of efficacy and tolerability in epilepsy clinical studies to provide a measure of effectiveness.
Time Frame	Duration of the Treatment Period (21 Weeks)

Outcome Measure Data

Analysis Population Description

The primary analysis consists of subjects in the Safety Set (SS). The SS is all subjects who received at least 1 dose of lacosamide.

Arm/Group Title	Lacosamide
Arm/Group Description:	Lacosamide will be added to levetiracetam while withdrawing the sodium channel blocking antiepileptic drug (AED). Lacosamide: 50 mg and 100 mg lacosamide tablets will be combined and taken in two equal doses per day to provide the required total daily dosage of 100 - 600 mg/day. Subjects were titrated to a minimum of 200 mg/ day during the Treatment Period. Maximum duration of study drug administration is approximately 23 weeks.
Overall Number of Participants Analyzed	120
Measure Type: Number; Unit of Measure: percentage of participants
	73.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lacosamide
	Comments	Analyses of the primary efficacy variable will be descriptive only. No hypothesis tests are planned. The number and percentage of subjects remaining in the study through the 21-Week Treatment Period will be calculated. Subjects with retention will be counted in the numerator. All subjects in the relevant population will be used as the denominator. This percentage will be known as the retention rate, along with the 95 % confidence interval based on the normal approximation.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Retention Rate
	Estimated Value	73.3
	Confidence Interval	(2-Sided) 95%; 65.42 to 81.25
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Treatment Emergent Adverse Events (TEAEs) were recorded during the course of the SP0980 study, which began in December 2011 and concluded in January 2014.
Adverse Event Reporting Description	TEAE reporting refers to the Safety Set (SS). The SS is all subjects who received at least 1 dose of lacosamide.
Arm/Group Title	Lacosamide
Arm/Group Description	Lacosamide will be added to levetiracetam while withdrawing the sodium channel blocking antiepileptic drug (AED). Lacosamide: 50 mg and 100 mg lacosamide tablets will be combined and taken in two equal doses per day to provide the required total daily dosage of 100 - 600 mg/day. Subjects were titrated to a minimum of 200 mg/ day during the Treatment Period. Maximum duration of study drug administration is approximately 23 weeks.
All-Cause Mortality
	Lacosamide
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Lacosamide
	Affected / at Risk (%)	# Events
Total	8/120 (6.67%)
Blood and lymphatic system disorders
Anaemia * 1	1/120 (0.83%)	1
Leukocytosis * 1	1/120 (0.83%)	1
Cardiac disorders
Acute Myocardial Infarction * 1	1/120 (0.83%)	1
Angina Pectoris * 1	1/120 (0.83%)	1
Gastrointestinal disorders
Toothache * 1	1/120 (0.83%)	1
Infections and infestations
Pneumonia * 1	2/120 (1.67%)	2
Appendicitis * 1	1/120 (0.83%)	1
Infection * 1	1/120 (0.83%)	1
Urinary Tract Infection * 1	1/120 (0.83%)	1
Vulvovaginitis Trichomonal * 1	1/120 (0.83%)	1
Nervous system disorders
Migraine * 1	1/120 (0.83%)	1
Psychiatric disorders
Anxiety * 1	1/120 (0.83%)	1
Mental Status Changes * 1	1/120 (0.83%)	1
Suicidal Ideation * 1	1/120 (0.83%)	1
Reproductive system and breast disorders
Asthma * 1	1/120 (0.83%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (9.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Lacosamide
	Affected / at Risk (%)	# Events
Total	52/120 (43.33%)
Gastrointestinal disorders
Nausea * 1	7/120 (5.83%)	7
General disorders
Fatigue * 1	10/120 (8.33%)	13
Nervous system disorders
Dizziness * 1	28/120 (23.33%)	40
Headache * 1	18/120 (15.00%)	21
Convulsion * 1	7/120 (5.83%)	8
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (9.1)

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 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 the results shall be published regardless of outcome.

Results Point of Contact

• Name/Title: Study Director
• Organization: UCB Clinical Trial Call Center
• Phone: +1 887 822 9493

Publications of Results:

Baulac M, Byrnes W, Williams P, Borghs S, Webster E, De Backer M, Dedeken P. Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy. Acta Neurol Scand. 2017 Apr;135(4):434-441. doi: 10.1111/ane.12691. Epub 2016 Oct 6.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT01484977
• Other Study ID Numbers: SP0980; 2011-002461-37 ( EudraCT Number )
• First Submitted: December 1, 2011
• First Posted: December 5, 2011
• Results First Submitted: November 20, 2014
• Results First Posted: November 26, 2014
• Last Update Posted: July 18, 2018