Trial Comparing the Efficacy and Safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR); Initial Monotherapy in Epilepsy; Subjects Aged 16 and Older (SP0993)

Study Description

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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).

Condition or disease	Intervention/treatment	Phase
Epilepsy; Monotherapy	Drug: Lacosamide; Drug: Carbamazepine-Controlled Release	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	888 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	A Multicenter, Double-blind, Double-dummy, Randomized, Positive- Controlled Study Comparing the Efficacy and Safety of Lacosamide (200 to 600 mg/Day) to Controlled Release Carbamazepine (400 to 1200 mg/Day), Used as Monotherapy in Subjects (≥ 16 Years) Newly or Recently Diagnosed With Epilepsy and Experiencing Partial-onset or Generalized Tonic-clonic Seizures.
Study Start Date :	April 2011
Actual Primary Completion Date :	July 2015
Actual Study Completion Date :	August 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Lacosamide	Drug: Lacosamide; Lacosamide: Strengths: 50 mg / 100 mg; Form: tablets; Dosage: total daily target dose of 200 mg, 400 mg or 600 mg. 1 dose reduction was allowed from either 600 mg to 500 mg or from 400 mg to 300 mg total daily dose; Duration: up to 118 weeks; Other Name: Vimpat®
Active Comparator: Carbamazepine-Controlled Release (CBZ-CR)	Drug: Carbamazepine-Controlled Release; Carbamazepine-CR: Strengths: 200 mg; Form: tablets; Dosage: total daily target dose of 400 mg, 800 mg or 1200 mg. 1 dose reduction was allowed from either 1200 mg to 1000 mg or from 800 mg to 600 mg total daily dose; Duration: up to 118 weeks; Other Name: Tegretol® Retard Tablets 200 mg

Outcome Measures

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Primary Outcome Measures :

1. 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 [ Time Frame: 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.
2. 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 [ Time Frame: 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.
3. Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks) [ Time Frame: 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.
4. Number of Subjects Who Withdraw From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (up to 113 Weeks) [ Time Frame: 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.
5. Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (up to 113 Weeks) [ Time Frame: 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 :

1. Proportion of Subjects Remaining Seizure Free for 12 Consecutive Months (52 Consecutive Weeks) Following Stabilization at the Last Evaluated Dose for Each Subject [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	16 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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Sponsors and Collaborators

UCB BIOSCIENCES GmbH

Eden Sarl

Investigators

Study Director:	UCB Cares	+1 877 822 9493 (UCB)

More Information

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Additional Information:

FDA Safety Alerts and Recalls 

Product Information 

Publications of Results:

Baulac M, Rosenow F, Toledo M, Terada K, Li T, De Backer M, Werhahn KJ, Brock M. Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol. 2017 Jan;16(1):43-54. doi: 10.1016/S1474-4422(16)30292-7. Epub 2016 Nov 24.

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

Lindauer A, Laveille C, Stockis A. Time-to-Seizure Modeling of Lacosamide Used in Monotherapy in Patients with Newly Diagnosed Epilepsy. Clin Pharmacokinet. 2017 Nov;56(11):1403-1413. doi: 10.1007/s40262-017-0530-8.

Responsible Party:	UCB BIOSCIENCES GmbH
ClinicalTrials.gov Identifier:	NCT01243177 History of Changes
Other Study ID Numbers:	SP0993; 2010-019765-28 ( EudraCT Number )
First Posted:	November 18, 2010
Results First Posted:	February 23, 2016
Last Update Posted:	October 26, 2017
Last Verified:	October 2017

Keywords provided by UCB Pharma ( UCB BIOSCIENCES GmbH ):

Lacosamide; Vimpat®; Epilepsy; Monotherapy; Velocity

Additional relevant MeSH terms:

Lacosamide; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carbamazepine; Anticonvulsants; Antimanic Agents; Tranquilizing Agents; Central Nervous System Depressants	Physiological Effects of Drugs; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 Enzyme Inducers; Molecular Mechanisms of Pharmacological Action