Study to Evaluate the Safety, Tolerability, and Efficacy of Long-term Adjunctive Therapy With Lacosamide in Adults With Partial-onset Seizures

Sponsor
UCB Pharma SA (Industry)
Overall Status
Completed
CT.gov ID
NCT01832038
Collaborator
UCB Japan Co. Ltd. (Industry)
473
67
1
76.2
7.1
0.1

Study Details

Study Description

Brief Summary

The purpose of this trial is to evaluate the safety and tolerability of long-term administration of Lacosamide at doses up to 400 mg/day in Japanese and Chinese adults with Epilepsy who have completed the Treatment and Transition Period of EP0008 [NCT01710657]

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
473 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-center, Open-label, Uncontrolled, Long-term, Extension Study to Evaluate the Safety and Efficacy of Lacosamide as Adjunctive Therapy in Japanese and Chinese Adults With Partial-onset Seizures With or Without Secondary Generalization
Actual Study Start Date :
Mar 26, 2013
Actual Primary Completion Date :
Jul 31, 2019
Actual Study Completion Date :
Jul 31, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lacosamide

Lacosamide treatment of 100 - 400 mg/day for long-term

Drug: Lacosamide
Strength: Lacosamide (LCM) 50 mg, LCM 100 mg Formulation: Tablet Frequency: twice daily during the study period (until the date of approval) At the completion of EP0008 [NCT01710657], all subjects who choose to enroll in EP0009 will be taking a dose of Lacosamide 200 mg/day. At the beginning of EP0009, the investigator may maintain the LCM dose or increase or decrease the dose. During the Treatment Period, the investigator will be allowed to increase or decrease the dose of LCM to optimize tolerability and seizure reduction. The LCM dose may be decreased to 100 mg/day or increased, no faster than 100 mg/day per week, up to 400 mg/day.
Other Names:
  • Vimpat
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With at Least One Adverse Event Reported Spontaneously by the Subject or Observed by the Investigator From Baseline Until the End of Study Visit [From Visit 1 (Week 0) up to approximately Week 323]

      An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could 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.

    2. Number of Participants That Withdrew Due to Adverse Events From Baseline Until the End of Study Visit [From Visit 1 (Week 0) up to approximately Week 323]

      An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment and led to the withdrawal of the participants from the study. An AE could 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.

    Secondary Outcome Measures

    1. Percent Change in Partial-onset Seizure Frequency Per 28 Days From Baseline of Study EP0008 [NCT01710657] Until the End of Study Visit in Study EP0009 [From Visit 1 in study EP0008 [NCT01710657] up to approximately Week 323 in study EP0009]

      The percent change from Baseline to the Treatment Period was calculated as {[(Seizure frequency per 28 days during the Treatment Period) minus (Seizure frequency per 28 days during Baseline Period)] divided by (Seizure frequency per 28 days during Baseline Period)} multiplied by 100. Baseline was defined as the Baseline Period of study EP0008 [NCT01710657].

    2. Percentage of Participants With 50 % Response Rate in Partial-onset Seizure Frequency Per 28 Days From Baseline of Study EP0008 [NCT01710657] Until the End of Study Visit in Study EP0009 [From Visit 1 in study EP0008 [NCT01710657] up to approximately Week 323 in study EP0009]

      A responder is a subject experiencing a greater than or equal to (≥) 50 % reduction in partial-onset seizure frequency per 28 days from baseline. Baseline was defined as the Baseline Period of study EP0008 [NCT01710657].

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Subject has completed the Treatment and Transition Period of EP0008 [NCT01710657]
    Exclusion Criteria:
    • Subjects who withdrew from EP0008 [NCT01710657]

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 86026 Beijing China
    2 86027 Beijing China
    3 86015 Changchun China
    4 86005 Chengdu China
    5 86032 Chengdu China
    6 86006 Chongqing China
    7 86031 Dalian China
    8 86007 Guangzhou China
    9 86008 Guangzhou China
    10 86009 Guangzhou China
    11 86013 Guangzhou China
    12 86016 Guangzhou China
    13 86014 Hangzhou China
    14 86010 Harbin China
    15 86019 Jinan China
    16 86004 Kunming China
    17 86011 Nanchang China
    18 86012 Nanchang China
    19 86028 Nanjing China
    20 86003 Qingdao China
    21 86001 Shanghai China
    22 86023 Shanghai China
    23 86025 Shanghai China
    24 86020 Shijiazhuang China
    25 86022 Suzhou China
    26 86002 Taiyuan China
    27 86018 Wuhan China
    28 86024 Wuhan China
    29 86017 Xi'an China
    30 86029 Xiamen China
    31 81056 Asaka Japan
    32 81013 Fukuoka Japan
    33 81054 Fukuoka Japan
    34 81057 Hachinohe Japan
    35 81027 Hamamatsu Japan
    36 81004 Himeji Japan
    37 81018 Hiroshima Japan
    38 81019 Iwanuma Japan
    39 81012 Kagoshima Japan
    40 81033 Kitakyushu Japan
    41 81017 Kobe Japan
    42 81024 Kodaira Japan
    43 81010 Kokubunji Japan
    44 81032 Koshi Japan
    45 81014 Kurume Japan
    46 81047 Kyoto Japan
    47 81035 Nagakute Japan
    48 81028 Nagoya Japan
    49 81029 Nagoya Japan
    50 81040 Nara Japan
    51 81007 Neyagawa Japan
    52 81002 Niigata Japan
    53 81005 Okayama Japan
    54 81009 Osakasayama Japan
    55 81011 Saitama Japan
    56 81042 Sakai Japan
    57 81025 Sapporo Japan
    58 81053 Sapporo Japan
    59 81021 Shimotsuke Japan
    60 81022 Shimotsuke Japan
    61 81026 Shinjuku Japan
    62 81003 Shizuoka Japan
    63 81023 Suita Japan
    64 81051 Suita Japan
    65 81006 Toyonaka Japan
    66 81050 Ube Japan
    67 81001 Yamagata Japan

    Sponsors and Collaborators

    • UCB Pharma SA
    • UCB Japan Co. Ltd.

    Investigators

    • Study Director: UCB Cares, +1 844 599 2273 (UCB)

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    UCB Pharma SA
    ClinicalTrials.gov Identifier:
    NCT01832038
    Other Study ID Numbers:
    • EP0009
    First Posted:
    Apr 15, 2013
    Last Update Posted:
    Aug 17, 2021
    Last Verified:
    Aug 1, 2021
    Keywords provided by UCB Pharma SA
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details The study started to enroll participants in March 2013 and concluded in July 2019.
    Pre-assignment Detail Participant Flow refers to the Safety Set.
    Arm/Group Title Lacosamide
    Arm/Group Description At the completion of EP0008 [NCT01710657], all participants who enrolled in EP0009 were administered a dose of 200 mg/day lacosamide (LCM). The LCM dose may have been decreased to 100 mg/day or increased, no faster than 100 mg/day per week, up to 400 mg/day, at the investigator's discretion.
    Period Title: Overall Study
    STARTED 473
    COMPLETED 238
    NOT COMPLETED 235

    Baseline Characteristics

    Arm/Group Title Lacosamide
    Arm/Group Description At the completion of EP0008 [NCT01710657], all participants who enrolled in EP0009 were administered a dose of 200 mg/day lacosamide (LCM). The LCM dose may have been decreased to 100 mg/day or increased, no faster than 100 mg/day per week, up to 400 mg/day, at the investigator's discretion.
    Overall Participants 473
    Age (Count of Participants)
    <=18 years
    39
    8.2%
    Between 18 and 65 years
    432
    91.3%
    >=65 years
    2
    0.4%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    32.7
    (12.0)
    Sex/Gender, Customized (Count of Participants)
    Male
    259
    54.8%
    Female
    214
    45.2%
    Race/Ethnicity, Customized (Count of Participants)
    Chinese
    350
    74%
    Japanese
    123
    26%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With at Least One Adverse Event Reported Spontaneously by the Subject or Observed by the Investigator From Baseline Until the End of Study Visit
    Description An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could 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.
    Time Frame From Visit 1 (Week 0) up to approximately Week 323

    Outcome Measure Data

    Analysis Population Description
    The Safety Set (SS) included all enrolled participants in EP0009 who took at least 1 dose of LCM in EP0009.
    Arm/Group Title Lacosamide (SS)
    Arm/Group Description At the completion of EP0008 [NCT01710657], all participants who enrolled in EP0009 were administered a dose of 200 mg/day LCM. The LCM dose may have been decreased to 100 mg/day or increased, no faster than 100 mg/day per week, up to 400 mg/day, at the investigator's discretion. Participants formed the Safety Set (SS).
    Measure Participants 473
    Count of Participants [Participants]
    410
    86.7%
    2. Primary Outcome
    Title Number of Participants That Withdrew Due to Adverse Events From Baseline Until the End of Study Visit
    Description An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment and led to the withdrawal of the participants from the study. An AE could 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.
    Time Frame From Visit 1 (Week 0) up to approximately Week 323

    Outcome Measure Data

    Analysis Population Description
    The Safety Set (SS) included all enrolled participants in EP0009 who took at least 1 dose of LCM in EP0009.
    Arm/Group Title Lacosamide (SS)
    Arm/Group Description At the completion of EP0008 [NCT01710657], all participants who enrolled in EP0009 were administered a dose of 200 mg/day LCM. The LCM dose may have been decreased to 100 mg/day or increased, no faster than 100 mg/day per week, up to 400 mg/day, at the investigator's discretion. Participants formed the Safety Set (SS).
    Measure Participants 473
    Count of Participants [Participants]
    51
    10.8%
    3. Secondary Outcome
    Title Percent Change in Partial-onset Seizure Frequency Per 28 Days From Baseline of Study EP0008 [NCT01710657] Until the End of Study Visit in Study EP0009
    Description The percent change from Baseline to the Treatment Period was calculated as {[(Seizure frequency per 28 days during the Treatment Period) minus (Seizure frequency per 28 days during Baseline Period)] divided by (Seizure frequency per 28 days during Baseline Period)} multiplied by 100. Baseline was defined as the Baseline Period of study EP0008 [NCT01710657].
    Time Frame From Visit 1 in study EP0008 [NCT01710657] up to approximately Week 323 in study EP0009

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) included all study participants from the SS who had at least 1 day with available seizure diary data in study EP0009.
    Arm/Group Title Lacosamide (FAS)
    Arm/Group Description At the completion of EP0008 [NCT01710657], all participants who enrolled in EP0009 were administered a dose of 200 mg/day LCM. The LCM dose may have been decreased to 100 mg/day or increased, no faster than 100 mg/day per week, up to 400 mg/day, at the investigator's discretion. Participants formed the Full Analysis Set (FAS).
    Measure Participants 471
    Mean (Standard Deviation) [Percent change]
    -44.47
    (55.82)
    4. Secondary Outcome
    Title Percentage of Participants With 50 % Response Rate in Partial-onset Seizure Frequency Per 28 Days From Baseline of Study EP0008 [NCT01710657] Until the End of Study Visit in Study EP0009
    Description A responder is a subject experiencing a greater than or equal to (≥) 50 % reduction in partial-onset seizure frequency per 28 days from baseline. Baseline was defined as the Baseline Period of study EP0008 [NCT01710657].
    Time Frame From Visit 1 in study EP0008 [NCT01710657] up to approximately Week 323 in study EP0009

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) included all study participants from the SS who had at least 1 day with available seizure diary data in study EP0009.
    Arm/Group Title Lacosamide (FAS)
    Arm/Group Description At the completion of EP0008 [NCT01710657], all participants who enrolled in EP0009 were administered a dose of 200 mg/day LCM. The LCM dose may have been decreased to 100 mg/day or increased, no faster than 100 mg/day per week, up to 400 mg/day, at the investigator's discretion. Participants formed the Full Analysis Set (FAS).
    Measure Participants 471
    Number [percentage of participants]
    57.1
    12.1%

    Adverse Events

    Time Frame Adverse Events were collected from Visit 1 (Week 0) up to approximately Week 323
    Adverse Event Reporting Description
    Arm/Group Title Lacosamide (SS)
    Arm/Group Description At the completion of EP0008 [NCT01710657], all participants who enrolled in EP0009 were administered a dose of 200 mg/day LCM. The LCM dose may have been decreased to 100 mg/day or increased, no faster than 100 mg/day per week, up to 400 mg/day, at the investigator's discretion. Participants formed the Safety Set (SS).
    All Cause Mortality
    Lacosamide (SS)
    Affected / at Risk (%) # Events
    Total 6/473 (1.3%)
    Serious Adverse Events
    Lacosamide (SS)
    Affected / at Risk (%) # Events
    Total 83/473 (17.5%)
    Cardiac disorders
    Sinus bradycardia 1/473 (0.2%) 1
    Congenital, familial and genetic disorders
    Hamartoma 1/473 (0.2%) 1
    Eye disorders
    Blindness unilateral 1/473 (0.2%) 1
    Gastrointestinal disorders
    Duodenitis 1/473 (0.2%) 1
    Dyspepsia 1/473 (0.2%) 1
    Gastric ulcer 1/473 (0.2%) 1
    Gastritis 2/473 (0.4%) 2
    Gastritis atrophic 1/473 (0.2%) 1
    Gastrointestinal haemorrhage 1/473 (0.2%) 1
    Gastrointestinal necrosis 1/473 (0.2%) 2
    Gastrointestinal pain 1/473 (0.2%) 1
    Haemorrhoids 1/473 (0.2%) 1
    Hypertrophic anal papilla 1/473 (0.2%) 1
    Inguinal hernia, obstructive 1/473 (0.2%) 1
    Large intestine polyp 1/473 (0.2%) 1
    Rectal polyp 1/473 (0.2%) 1
    Rectal prolapse 1/473 (0.2%) 1
    Reflux gastritis 1/473 (0.2%) 1
    General disorders
    Pyrexia 1/473 (0.2%) 1
    Sudden death 1/473 (0.2%) 1
    Hepatobiliary disorders
    Cholecystitis 1/473 (0.2%) 1
    Infections and infestations
    Bacterial prostatitis 1/473 (0.2%) 1
    Chronic sinusitis 2/473 (0.4%) 2
    Encephalitis viral 1/473 (0.2%) 1
    Erysipelas 1/473 (0.2%) 1
    Gastroenteritis 1/473 (0.2%) 1
    Lung infection 1/473 (0.2%) 1
    Orchitis 1/473 (0.2%) 1
    Peritonitis 1/473 (0.2%) 1
    Peritonsillar abscess 1/473 (0.2%) 1
    Pneumonia 6/473 (1.3%) 6
    Retroperitoneal infection 1/473 (0.2%) 1
    Tuberculosis of genitourinary system 1/473 (0.2%) 1
    Upper respiratory tract infection 2/473 (0.4%) 3
    Injury, poisoning and procedural complications
    Ankle fracture 1/473 (0.2%) 1
    Brain contusion 1/473 (0.2%) 1
    Burns third degree 1/473 (0.2%) 1
    Clavicle fracture 2/473 (0.4%) 2
    Craniocerebral injury 1/473 (0.2%) 1
    Face injury 1/473 (0.2%) 1
    Facial bones fracture 2/473 (0.4%) 3
    Fibula fracture 1/473 (0.2%) 1
    Foreign body 1/473 (0.2%) 3
    Head injury 1/473 (0.2%) 1
    Heat stroke 1/473 (0.2%) 1
    Humerus fracture 1/473 (0.2%) 1
    Injury 2/473 (0.4%) 2
    Jaw fracture 2/473 (0.4%) 2
    Spinal compression fracture 1/473 (0.2%) 1
    Subdural haemorrhage 1/473 (0.2%) 1
    Thermal burn 1/473 (0.2%) 2
    Tibia fracture 1/473 (0.2%) 1
    Toxicity to various agents 1/473 (0.2%) 1
    Metabolism and nutrition disorders
    Decreased appetite 1/473 (0.2%) 2
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 1/473 (0.2%) 1
    Rhabdomyolysis 1/473 (0.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer 1/473 (0.2%) 1
    Haemangioma 1/473 (0.2%) 1
    Meigs' syndrome 1/473 (0.2%) 1
    Metastatic glioma 1/473 (0.2%) 1
    Ovarian fibroma 1/473 (0.2%) 1
    Ovarian germ cell teratoma 1/473 (0.2%) 1
    Nervous system disorders
    Cerebral haemorrhage 1/473 (0.2%) 1
    Cerebral infarction 2/473 (0.4%) 2
    Complex partial seizures 1/473 (0.2%) 1
    Convulsion 3/473 (0.6%) 3
    Epilepsy 10/473 (2.1%) 10
    Grand mal convulsion 1/473 (0.2%) 1
    Haemorrhage intracranial 1/473 (0.2%) 1
    Headache 1/473 (0.2%) 1
    Hypoxic-ischaemic encephalopathy 1/473 (0.2%) 1
    Intracranial haematoma 1/473 (0.2%) 1
    Partial seizures with secondary generalisation 1/473 (0.2%) 1
    Seizure cluster 1/473 (0.2%) 2
    Status epilepticus 11/473 (2.3%) 13
    Subarachnoid haemorrhage 2/473 (0.4%) 2
    Temporal lobe epilepsy 1/473 (0.2%) 1
    Transient ischaemic attack 1/473 (0.2%) 1
    Visual field defect 1/473 (0.2%) 1
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 1/473 (0.2%) 1
    Pregnancy on contraceptive 1/473 (0.2%) 1
    Psychiatric disorders
    Epileptic psychosis 3/473 (0.6%) 3
    Hallucination 1/473 (0.2%) 1
    Mental disorder 1/473 (0.2%) 1
    Suicidal ideation 1/473 (0.2%) 1
    Suicide attempt 1/473 (0.2%) 1
    Renal and urinary disorders
    Renal impairment 1/473 (0.2%) 1
    Reproductive system and breast disorders
    Prostatitis 1/473 (0.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Asthma 1/473 (0.2%) 1
    Haemoptysis 1/473 (0.2%) 1
    Nasal septum deviation 2/473 (0.4%) 2
    Rhinitis allergic 1/473 (0.2%) 1
    Vocal cord leukoplakia 1/473 (0.2%) 1
    Surgical and medical procedures
    Abortion induced 3/473 (0.6%) 3
    Wisdom teeth removal 2/473 (0.4%) 2
    Vascular disorders
    Varicose vein 1/473 (0.2%) 1
    Venous occlusion 1/473 (0.2%) 1
    Other (Not Including Serious) Adverse Events
    Lacosamide (SS)
    Affected / at Risk (%) # Events
    Total 343/473 (72.5%)
    Eye disorders
    Vision blurred 22/473 (4.7%) 29
    Gastrointestinal disorders
    Abdominal pain upper 28/473 (5.9%) 57
    Diarrhoea 41/473 (8.7%) 64
    Nausea 30/473 (6.3%) 46
    Toothache 38/473 (8%) 47
    Vomiting 37/473 (7.8%) 66
    General disorders
    Pyrexia 41/473 (8.7%) 53
    Infections and infestations
    Gastroenteritis 27/473 (5.7%) 36
    Nasopharyngitis 156/473 (33%) 510
    Pharyngitis 22/473 (4.7%) 38
    Upper respiratory tract infection 99/473 (20.9%) 208
    Injury, poisoning and procedural complications
    Contusion 27/473 (5.7%) 37
    Nervous system disorders
    Dizziness 125/473 (26.4%) 318
    Headache 77/473 (16.3%) 177
    Somnolence 41/473 (8.7%) 80
    Psychiatric disorders
    Insomnia 26/473 (5.5%) 32
    Respiratory, thoracic and mediastinal disorders
    Cough 27/473 (5.7%) 43
    Oropharyngeal pain 27/473 (5.7%) 48

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title UCB
    Organization Cares
    Phone +1844 599 ext 2273
    Email UCBCares@ucb.com
    Responsible Party:
    UCB Pharma SA
    ClinicalTrials.gov Identifier:
    NCT01832038
    Other Study ID Numbers:
    • EP0009
    First Posted:
    Apr 15, 2013
    Last Update Posted:
    Aug 17, 2021
    Last Verified:
    Aug 1, 2021