Study to Evaluate the Safety, Tolerability, and Efficacy of Long-term Adjunctive Therapy With Lacosamide in Adults With Partial-onset Seizures
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
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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
- 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].
- 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
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.- EP0009
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
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%
|
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%
|
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)
|
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
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 |
UCBCares@ucb.com |
- EP0009