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Evaluating Long Term Safety of Lacosamide (LCM) to Carbamazepine Controlled-release (CBZ-CR); Initial Monotherapy in Epilepsy Subjects 16 Years and Older

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01465997
Recruitment Status : Completed
First Posted : November 7, 2011
Results First Posted : August 2, 2017
Last Update Posted : July 18, 2018
Sponsor:
Collaborator:
Eden Sarl
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES GmbH )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Epilepsy
Monotherapy
Interventions Drug: Lacosamide
Drug: Carbamazepine-Controlled Release (CBZ-CR)
Enrollment 551
Recruitment Details Enrollment started in May 2012 and concluded in January 2017 - 551 patients. Due to the political and civil unrest in Luhansk PAREXEL was not able to conduct further site visits to one site in Ukraine and to collect further data for 2 subjects,they were excluded from SP0994, leaving 549 patients in the Enrolled Set out of 551 initially enrolled.
Pre-assignment Details

A total of 549 subjects gave informed consent in SP0994 and were included in the Enrolled Set, 548 subjects received at least 1 dose of study medication and were included in the Safety Set (SS).

Participant Flow refers to the Safety Population including all enrolled subjects who received at least 1 dose of study medication in the current study.

Arm/Group Title Lacosamide Carbamazepine-Controlled Release (CBZ-CR)
Hide Arm/Group Description 50 and 100 mg tablets of Lacosamide given as 200 mg/day, 300 mg/day, 400 mg/day, 500 mg/day or 600 mg/day throughout the Treatment Period (Maximum 3.5 Years). CBZ-CR placebo capsules were administered to maintain the blinding. 200 mg tablets of Carbamazepine-CR given as 400 mg/day, 600 mg/day, 800 mg/day, 1000 mg/day or 1200 mg/day throughout the Treatment Period (Maximum of 3.5 Years). Lacosamide placebo capsules were administered to maintain the blinding.
Period Title: Overall Study
Started 279 269
Completed 211 180
Not Completed 68 89
Reason Not Completed
Adverse Event             12             22
Lack of Efficacy             13             1
Protocol Violation             1             4
Lost to Follow-up             6             9
Withdrawal by Subject             32             35
investigator's decision             1             1
Death             0             1
sponsor's decision             1             1
subject withdrew consent             1             0
local lab unblinded site             1             0
withdrew before follow-up             0             13
decision by site staff             0             1
subject left participation SP0993             0             1
Arm/Group Title Lacosamide Carbamazepine-Controlled Release (CBZ-CR) Total Title
Hide Arm/Group Description 50 and 100 mg tablets of Lacosamide given as 200 mg/day, 300 mg/day, 400 mg/day, 500 mg/day or 600 mg/day throughout the Treatment Period (Maximum 3.5 Years). CBZ-CR placebo capsules were administered to maintain the blinding. 200 mg tablets of Carbamazepine-CR given as 400 mg/day, 600 mg/day, 800 mg/day, 1000 mg/day or 1200 mg/day throughout the Treatment Period (Maximum of 3.5 Years). Lacosamide placebo capsules were administered to maintain the blinding. [Not Specified]
Overall Number of Baseline Participants 279 269 548
Hide Baseline Analysis Population Description
The analysis group for Baseline Characteristics is the Safety Set (SS). The SS consists of all subjects in the Enrolled Set who have received at least 1 dose of study medication.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 279 participants 269 participants 548 participants
<=18 years
8
   2.9%
8
   3.0%
16
   2.9%
Between 18 and 65 years
230
  82.4%
225
  83.6%
455
  83.0%
>=65 years
41
  14.7%
36
  13.4%
77
  14.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 279 participants 269 participants 548 participants
43.2  (17.2) 42.7  (16.7) 42.9  (17.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 279 participants 269 participants 548 participants
Female
125
  44.8%
125
  46.5%
250
  45.6%
Male
154
  55.2%
144
  53.5%
298
  54.4%
1.Primary Outcome
Title Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum of 3.5 Years)
Hide Description Treatment-emergent AEs were defined as those events which started on or after the date of first dose of SP0994 study medication, or events in which severity worsened on or after the date of first dose of SP0994 study medication. AEs which occurred within 30 days after last dose of study medication were considered treatment emergent.
Time Frame Up to 3.5 Years (Duration of the Treatment Phase)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lacosamide (SS) Carbamazepine-Controlled Release (CBZ-CR) (SS)
Hide Arm/Group Description:
50 and 100 mg tablets of Lacosamide given as 200 mg/day, 300 mg/day, 400 mg/day, 500 mg/day or 600 mg/day throughout the Treatment Period (Maximum 3.5 Years). CBZ-CR placebo capsules were administered to maintain the blinding.
200 mg tablets of Carbamazepine-CR given as 400 mg/day, 600 mg/day, 800 mg/day, 1000 mg/day or 1200 mg/day throughout the Treatment Period (Maximum of 3.5 Years). Lacosamide placebo capsules were administered to maintain the blinding.
Overall Number of Participants Analyzed 279 269
Measure Type: Count of Participants
Unit of Measure: Participants
181
  64.9%
182
  67.7%
2.Primary Outcome
Title Number of Subjects Who Withdrew From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum 3.5 Years)
Hide Description Treatment-emergent AEs were defined as those events which started on or after the date of first dose of SP0994 study medication, or events in which severity worsened on or after the date of first dose of SP0994 study medication. AEs which occurred within 30 days after last dose of study medication were considered treatment emergent.
Time Frame Up to 3.5 Years (Duration of the Treatment Phase)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lacosamide Carbamazepine-Controlled Release (CBZ-CR)
Hide Arm/Group Description:
50 and 100 mg tablets of Lacosamide given as 200 mg/day, 300 mg/day, 400 mg/day, 500 mg/day or 600 mg/day throughout the Treatment Period (Maximum 3.5 Years). CBZ-CR placebo capsules were administered to maintain the blinding.
200 mg tablets of Carbamazepine-CR given as 400 mg/day, 600 mg/day, 800 mg/day, 1000 mg/day or 1200 mg/day throughout the Treatment Period (Maximum of 3.5 Years). Lacosamide placebo capsules were administered to maintain the blinding.
Overall Number of Participants Analyzed 279 269
Measure Type: Count of Participants
Unit of Measure: Participants
12
   4.3%
21
   7.8%
3.Primary Outcome
Title Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (Maximum of 3.5 Years)
Hide Description A Serious Adverse Event is any untoward medical occurrence that at any dose results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity is a congenital anomaly/birth defect.
Time Frame Up to 3.5 Years (Duration of the Treatment Phase)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lacosamide Carbamazepine-Controlled Release (CBZ-CR)
Hide Arm/Group Description:
50 and 100 mg tablets of Lacosamide given as 200 mg/day, 300 mg/day, 400 mg/day, 500 mg/day or 600 mg/day throughout the Treatment Period (Maximum 3.5 Years). CBZ-CR placebo capsules were administered to maintain the blinding.
200 mg tablets of Carbamazepine-CR given as 400 mg/day, 600 mg/day, 800 mg/day, 1000 mg/day or 1200 mg/day throughout the Treatment Period (Maximum of 3.5 Years). Lacosamide placebo capsules were administered to maintain the blinding.
Overall Number of Participants Analyzed 279 269
Measure Type: Count of Participants
Unit of Measure: Participants
32
  11.5%
22
   8.2%
Time Frame During the entire study period, up to 5 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lacosamide (SS) Carbamazepine-Controlled Release (CBZ-CR) (SS)
Hide Arm/Group Description 50 and 100 mg tablets of Lacosamide given as 200 mg/day, 300 mg/day, 400 mg/day, 500 mg/day or 600 mg/day throughout the Treatment Period (Maximum 3.5 Years). CBZ-CR placebo capsules were administered to maintain the blinding. 200 mg tablets of Carbamazepine-CR given as 400 mg/day, 600 mg/day, 800 mg/day, 1000 mg/day or 1200 mg/day throughout the Treatment Period (Maximum of 3.5 Years). Lacosamide placebo capsules were administered to maintain the blinding.
All-Cause Mortality
Lacosamide (SS) Carbamazepine-Controlled Release (CBZ-CR) (SS)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Lacosamide (SS) Carbamazepine-Controlled Release (CBZ-CR) (SS)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/279 (11.47%)      22/269 (8.18%)    
Blood and lymphatic system disorders     
Eosinophilia * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Cardiac disorders     
Angina pectoris * 1  2/279 (0.72%)  2 0/269 (0.00%)  0
Atrial fibrillation * 1  1/279 (0.36%)  1 1/269 (0.37%)  1
Acute myocardial infarction * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Cardiac failure * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Myocardial ischaemia * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Atrioventricular block second degree * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Ear and labyrinth disorders     
Vestibular ataxia * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Eye disorders     
Exophthalmos * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Gastrointestinal disorders     
Lumbar hernia * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Mallory-Weiss syndrome * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Umbilical hernia * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Abdominal pain lower * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Gastric ulcer * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Rectal haemorrhage * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Hepatobiliary disorders     
Gallbladder disorder * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Hepatic cirrhosis * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Infections and infestations     
Appendicitis * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Infective exacerbation of chronic obstructive airways disease * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Gastroenteritis * 1  0/279 (0.00%)  0 3/269 (1.12%)  4
Post procedural infection * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Injury, poisoning and procedural complications     
Laceration * 1  1/279 (0.36%)  1 1/269 (0.37%)  1
Fall * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Joint dislocation * 1  1/279 (0.36%)  2 0/269 (0.00%)  0
Ligament rupture * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Radius fracture * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Femoral neck fracture * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Head injury * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Humerus fracture * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Intentional overdose * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Ligament sprain * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Periorbital haematoma * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Skull fracture * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Subdural haematoma * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Toxicity to various agents * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Investigations     
Hepatic enzyme increased * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Metabolism and nutrition disorders     
Hyponatraemia * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  1/279 (0.36%)  2 1/269 (0.37%)  1
Bone lesion * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Dupuytren's contracture * 1  1/279 (0.36%)  2 0/269 (0.00%)  0
Pain in extremity * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Arthropathy * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Joint instability * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Osteoarthritis * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Breast cancer * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Central nervous system lymphoma * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Myelodysplastic syndrome * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Benign breast neoplasm * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Endometrial adenocarcinoma * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Glioblastoma multiforme * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Thyroid neoplasm * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Uterine cancer * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Nervous system disorders     
Transient ischaemic attack * 1  2/279 (0.72%)  2 0/269 (0.00%)  0
Cerebral ischaemia * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Cervicobrachial syndrome * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Cognitive disorder * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Dizziness * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Grand mal convulsion * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Ischaemic stroke * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Status epilepticus * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Syncope * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
White matter lesion * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Convulsion * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Hemiparesis * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Reversible ischaemic neurological deficit * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Subarachnoid haemorrhage * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Pregnancy, puerperium and perinatal conditions     
Pregnancy on contraceptive * 1  0/279 (0.00%)  0 2/269 (0.74%)  2
Psychiatric disorders     
Suicidal ideation * 1  1/279 (0.36%)  1 2/269 (0.74%)  2
Adjustment disorder with depressed mood * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Suicidal behaviour * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Suicide attempt * 1  0/279 (0.00%)  0 2/269 (0.74%)  2
Renal and urinary disorders     
Renal failure acute * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Reproductive system and breast disorders     
Epididymitis * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary oedema * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
Skin and subcutaneous tissue disorders     
Urticaria * 1  0/279 (0.00%)  0 1/269 (0.37%)  1
Vascular disorders     
Hypertension * 1  1/279 (0.36%)  1 0/269 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lacosamide (SS) Carbamazepine-Controlled Release (CBZ-CR) (SS)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/279 (16.13%)      42/269 (15.61%)    
Infections and infestations     
Nasopharyngitis * 1  20/279 (7.17%)  40 16/269 (5.95%)  22
Nervous system disorders     
Headache * 1  17/279 (6.09%)  28 16/269 (5.95%)  26
Dizziness * 1  12/279 (4.30%)  13 17/269 (6.32%)  19
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA16.1
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.
Results Point of Contact
Name/Title: UCB
Organization: Cares
Phone: +1844 599 ext 2273
Responsible Party: UCB Pharma ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier: NCT01465997     History of Changes
Other Study ID Numbers: SP0994
2010-021238-74 ( EudraCT Number )
First Submitted: November 2, 2011
First Posted: November 7, 2011
Results First Submitted: June 27, 2017
Results First Posted: August 2, 2017
Last Update Posted: July 18, 2018