Trial Comparing the Efficacy and Safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR); Initial Monotherapy in Epilepsy; Subjects Aged 16 and Older

Phase 3

Completed

Conditions: Epilepsy
Monotherapy

Interventions: Drug: Carbamazepine-Controlled Release
Drug: Lacosamide

Registration Number: NCT01243177

Lead Sponsor: UCB BIOSCIENCES GmbH

Brief Summary: Compare efficacy and safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR) as monotherapy in newly or recently newly diagnosed subjects with a primary efficacy endpoint of 6-month seizure freedom. Noninferiority design to show a similar risk/benefit balance between Lacosamide (LCM) and Carbamazepine-CR (CBZ-CR).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 888

Inclusion Criteria

Subject able to comply with study requirements
Subject is 16 years and older (female; male). Minors will be included in countries only if legally permitted
Subject has newly or recently diagnosed Epilepsy experiencing partial onset seizures (POS) or generalized tonic-clonic seizures with at least 2 unprovoked seizures separated by 48 hours in the 12 months preceding Visit 1 out of which at least 1 seizure occured 3 months preceding Visit 1
Subject has had an Electroencephalogram (EEG) and a brain Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI) exam of the brain within the past 12 months. If the EEG and brain CT scan or MRI exam were not performed prior to Visit 1, they need to be completed and results must be available prior to randomization at Visit 2

Exclusion Criteria

Subject has a history or presence of seizures of other types than partial-onset (IA, IB, IC with clear focal origin) and generalized tonic-clonic (without clear focal origin) seizures (eg, myoclonic, absence)
Subject has a history or presence of seizures occurring only in clustered patterns, defined as repeated seizures occurring over a short period of time (ie, < 20 minutes) with or without function regained between 2 ictal events
Subject has a history, clinical, or Electroencephalogram (EEG) finding suggestive of Idiopathic Generalized Epilepsy (IGE) at randomization
Subject has current or previous diagnosis of pseudoseizures, conversion disorders, or other nonepileptic ictal events that could be confused with seizures based on expert opinion and/or EEG evidence
Subject has any medical or psychiatric condition
Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening
Subject has received treatment with Phenobarbital or Primidone within 28 days prior to Visit 1
Subject is taking Benzodiazepines for a nonepilepsy indication
Subject has been treated for Epilepsy with any Antiepileptic Drug (AED) (including Benzodiazepines) in the last 6 months before Visit. However, acute and subacute seizure treatment is accepted with a maximum of 2 weeks duration and if treatment was stopped at least 3 days prior to randomization
Prior use of Felbamate or Vigabatrin is not allowed
Benzodiazepines as rescue therapy for Epilepsy may have been used as needed in this time period, but not more frequently than once per week
Subject has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion, has a history of alcohol or drug abuse within the previous 2 years
Asian ancestry and tests positive for HLA-B*1502 allele
Asian ancestry and tests positive for HLA-A*3101 allele

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carbamazepine-Controlled Release (CBZ-CR)	Carbamazepine-Controlled Release	-
Lacosamide	Lacosamide	-

Primary Outcome Measures

Name	Time	Method
Proportion of Subjects in the Full Analysis Set (FAS) Remaining Seizure Free for 6 Consecutive Months (26 Consecutive Weeks) of Treatment Following Stabilization at the Last Evaluated Dose for Each Subject	6 consecutive months (26 consecutive weeks) of treatment following stabilization at the last evaluated dose for each subject	The proportion of subjects remaining seizure free for 6 months (26 weeks) was estimated using Kaplan-Meier methods.
Proportion of Subjects in the Per Protocol Set (PPS) Remaining Seizure Free for 6 Consecutive Months (26 Consecutive Weeks) of Treatment Following Stabilization at the Last Evaluated Dose for Each Subject	6 consecutive months (26 consecutive weeks) of treatment	The proportion of subjects remaining seizure free for 6 months (26 weeks) was estimated using Kaplan-Meier methods.
Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks)	Duration of the Treatment Phase (up to 113 weeks)	An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent AEs were defined as AEs that started on or after the date of first dose of study medication and within 30 days following the date of final study medication administration, or AEs whose intensity worsened on or after the date of first dose of study medication and within 30 days following the date of last dose.
Number of Subjects Who Withdraw From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks)	Duration of the Treatment Phase (up to 113 weeks)	An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent AEs were defined as AEs that started on or after the date of first dose of study medication and within 30 days following the date of final study medication administration, or AEs whose intensity worsened on or after the date of first dose of study medication and within 30 days following the date of last dose.
Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (up to 113 Weeks)	Duration of the Treatment Phase (up to 113 weeks)	An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A Serious Adverse Event must meet 1 or more predefined criteria like death, life-threatening, etc. Treatment-emergent AEs were defined as AEs that started on or after the date of first dose of study medication and within 30 days following the date of final study medication administration, or AEs whose intensity worsened on or after the date of first dose of study medication and within 30 days following the date of last dose.

Secondary Outcome Measures

Name	Time	Method
Proportion of Subjects Remaining Seizure Free for 12 Consecutive Months (52 Consecutive Weeks) Following Stabilization at the Last Evaluated Dose for Each Subject	12 consecutive months of treatment following stabilization at the last evaluated dose for each subject	The proportion of subjects remaining seizure free for 12 months (52 weeks) was estimated using Kaplan-Meier methods.

Trial Locations

Locations (184): 786
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Alabaster, Alabama, United States
799
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Huntsville, Alabama, United States
780
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Phoenix, Arizona, United States
777
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Little Rock, Arkansas, United States
795
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Ocala, Florida, United States
789
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Panama City, Florida, United States
776
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Port Charlotte, Florida, United States
779
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Manhattan, Kansas, United States
874
🇺🇸
Charlotte, North Carolina, United States
876
🇺🇸
Hickory, North Carolina, United States
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786
🇺🇸Alabaster, Alabama, United States