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

Purpose

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	Intervention	Phase
Epilepsy Monotherapy	Drug: Lacosamide Drug: Carbamazepine-Controlled Release	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures

Drug Information available for: Carbamazepine Carbamazepine dihydrate Lacosamide

U.S. FDA Resources

Further study details as provided by UCB Pharma:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 [ Time Frame: 6 consecutive months (26 consecutive weeks) of treatment ] [ Designated as safety issue: No ]
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) [ Time Frame: Duration of the Treatment Phase (up to 113 weeks) ] [ Designated as safety issue: No ]
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) [ Time Frame: Duration of the Treatment Phase (up to 113 weeks) ] [ Designated as safety issue: No ]
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) [ Time Frame: Duration of the Treatment Phase (up to 113 weeks) ] [ Designated as safety issue: No ]
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:

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 ] [ Designated as safety issue: No ]
The proportion of subjects remaining seizure free for 12 months (52 weeks) was estimated using Kaplan-Meier methods.


Enrollment:	888
Study Start Date:	April 2011
Study Completion Date:	August 2015
Primary Completion Date:	July 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	16 Years and older (Child, Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01243177

Show 184 Study Locations

Sponsors and Collaborators

UCB BIOSCIENCES GmbH

Eden Sarl

Investigators


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

More Information

Additional Information:

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

Product Information This link exits the ClinicalTrials.gov site


Responsible Party:	UCB BIOSCIENCES GmbH
ClinicalTrials.gov Identifier:	NCT01243177 History of Changes
Other Study ID Numbers:	SP0993 2010-019765-28
Study First Received:	November 16, 2010
Results First Received:	January 25, 2016
Last Updated:	January 25, 2016
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: Federal Agency for Medicinal Products and Health Products Canada: Health Canada Czech Republic: State Institute for Drug Control Finland: Finnish Medicines Agency France: Agence Nationale de Sécurité du Médicament et des produits de santé Germany: Federal Institute for Drugs and Medical Devices Greece: National Organization of Medicines Hungary: National Institute of Pharmacy Italy: The Italian Medicines Agency Mexico: Federal Commission for Protection Against Health Risks Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Portugal: National Pharmacy and Medicines Institute Romania: National Medicines Agency Russia: Ministry of Health of the Russian Federation Slovakia: State Institute for Drug Control Spain: Agencia Española de Medicamentos y Productos Sanitarios South Korea: Korea Food and Drug Administration (KFDA) Sweden: Medical Products Agency Ukraine: State Pharmacological Center - Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency Switzerland: Swissmedic Thailand: Ministry of Public Health Philippines: Bureau of Food and Drugs Lithuania: State Medicine Control Agency - Ministry of Health Bulgaria: Bulgarian Drug Agency Latvia: State Agency of Medicines Japan: Pharmaceuticals and Medical Devices Agency United States: Food and Drug Administration

Keywords provided by UCB Pharma:


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

ClinicalTrials.gov processed this record on September 26, 2016

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)