Add on Lacosamide Versus High Dose Monotherapy

Open Label Trial of Add on Lacosamide Versus High Dose Monotherapy in Patients With a Seizure Disorder

This is a study to determine whether a combination of low dose lacosamide and levetiracetam is more effective than high dose levetiracetam in patients who have failed low dose levetiracetam.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: lacosamide; Drug: levetiracetam

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults age 18 or older
2. Determined to have had at least two partial seizures by an epilepsy specialist, or to have had a single partial seizure with clinical and/or laboratory evidence of a high seizure recurrence risk
3. Monotherapy on levetiracetam less than or equal to 1500 mg/day for at least two weeks
4. Breakthrough seizure while on stable dose (>5 days) of levetiracetam monotherapy regimen, not due to provocative factors (e.g. hypoglycemia, head trauma, missed medications)

Exclusion Criteria:

1. Clinical suspicion of nonepileptic psychogenic seizures or idiopathic generalized epilepsy
2. Pregnant, child-bearing age not using contraception, or breast feeding
3. Medical contraindication to adding lacosamide
4. History of antiepileptic drug (AED) polytherapy
5. Presence of a vagus nerve stimulator
6. Creatinine clearance of less than 50 mL/min
7. Blood pressure instability: pulse <50 or >100, systolic blood pressure (SBP) <50 or >180, clinically significant electrocardiogram (EKG) abnormality
8. History of significant drug rash or anaphylactic reaction with antiepileptic drug
9. Patients with progressive lesions (e.g. brain tumors)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lacosamide + Low-Dose Levetiracetam; Participants received lacosamide 50 mg twice a day for one week followed by 100 mg twice daily added to low dose levetiracetam ≤1500 mg/day (polytherapy) for 6 months in patients with breakthrough seizures on low-dose levetiracetam.	Drug: lacosamide; Lacosamide maximum of 200 mg/day, to be titrated as follows: Week 1: 50 mg twice a day; Beginning Week 2: 100 mg twice a day.; Other Names: Vimpat; Drug: levetiracetam; Low dose ≤1500 mg/day, High dose >1500 mg/day
Other: Control Group (High-Dose Levetiracetam); Historical chart review of patients whose dose of levetiracetam was raised to high dose levetiracetam >1500 mg/day (monotherapy) after a breakthrough seizure. No intervention was administered in the study.	Drug: levetiracetam; Low dose ≤1500 mg/day, High dose >1500 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Six Month Seizure Freedom	Seizure freedom is defined as having no seizures and was evaluated in the 6 month period after receiving the drug.	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seizure-Free Days		6 Months
Time to First Seizure After Therapeutic Dose is Reached	Time in days until the first seizure after the therapeutic dose is reached occurs.	6 Months
Retention Rate	Retention rate is defined as the percentage of participants who remained on the study drug after study completion.	6 Months
Number of Participants With Treatment-Emergent Adverse Events (TEAE)	An Adverse Event (AE) is defined as any untoward medical occurrence (side effect) in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event that occurs after receiving the drug.	6 Months

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Jong Woo Lee, MD, PhD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Lee JW, Alam J, Llewellyn N, Hurwitz S, Bubrick EB, Sarkis RA, Weisholtz D, Yu H, Putta S, Dworetzky BA, Pennell PB. Open Label Trial of Add on Lacosamide Versus High Dose Levetiracetam Monotherapy in Patients With Breakthrough Seizures. Clin Neuropharmacol. 2016 May-Jun;39(3):128-31. doi: 10.1097/WNF.0000000000000144.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2011
• Primary Completion (Actual): February 15, 2014
• Study Completion (Actual): October 21, 2014

Study Registration Dates

• First Submitted: April 28, 2011
• First Submitted That Met QC Criteria: April 28, 2011
• First Posted (Estimated): April 29, 2011

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Epilepsy; polytherapy; antiepileptic drug
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acids, Acyclic; Carboxylic Acids; Amides; Pyrrolidines; Acetamides; Acetates; Pyrrolidinones; Lacosamide; Levetiracetam
• Other Study ID Numbers: 2010-P-001630