Trial Outcomes & Findings for A Trial to Evaluate the Long Term Safety and Tolerability of Lacosamide Taken as Monotherapy in Adults With Partial-onset Seizures (NCT NCT02124564)

Last Updated: 2019-10-28

Results Overview

An Adverse Event (AE) 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 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

19 participants

Primary outcome timeframe

From the Titration Period (investigational product is taken) to the End of Study Visit (up to 3.5 years)

Results posted on

2019-10-28

Participant Flow

The study started to enroll patients in April 2014 and concluded in November 2017.

Participant flow refers to Safety Set including all subjects which took at least one dose of study medication.

Participant milestones

Participant milestones
Measure	Lacosamide Subjects randomized in this arm received lacosamide from 200 mg/day to 600 mg/day, from the Titration to the End of Study Visit (up to 3.5 years).
Treatment Period STARTED	19
Treatment Period Started Treatment Period	19
Treatment Period Started Titration Period	19
Treatment Period Started AED Withdrawal Period	19
Treatment Period Started Monotherapy Period	17
Treatment Period Started Evaluation Period	17
Treatment Period Started Follow-Up Period	13
Treatment Period COMPLETED	12
Treatment Period NOT COMPLETED	7
Taper Period STARTED	2
Taper Period COMPLETED	2
Taper Period NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Lacosamide Subjects randomized in this arm received lacosamide from 200 mg/day to 600 mg/day, from the Titration to the End of Study Visit (up to 3.5 years).
Treatment Period Adverse Event	2
Treatment Period Lack of Efficacy	3
Treatment Period Withdrawal by Subject	2

Baseline Characteristics

A Trial to Evaluate the Long Term Safety and Tolerability of Lacosamide Taken as Monotherapy in Adults With Partial-onset Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lacosamide n=19 Participants Subjects randomized in this arm received lacosamide from 200 mg/day to 600 mg/day, from the Titration to the End of Study Visit (up to 3.5 years).
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=99 Participants
Age, Categorical >=65 years	2 Participants n=99 Participants
Age, Continuous	39.2 years STANDARD_DEVIATION 15.8 • n=99 Participants
Sex: Female, Male Female	8 Participants n=99 Participants
Sex: Female, Male Male	11 Participants n=99 Participants
Race/Ethnicity, Customized Asian (Japanese)	19 Participants n=99 Participants
Race/Ethnicity, Customized Other	0 Participants n=99 Participants

PRIMARY outcome

Timeframe: From the Titration Period (investigational product is taken) to the End of Study Visit (up to 3.5 years)

Outcome measures

Outcome measures
Measure	Lacosamide (Safety Set) n=19 Participants Subjects randomized in this arm received lacosamide from 200 mg/day to 600 g/day, from the Titration to the End of Study Visit (up to 3.5 years).
Number of Subjects With at Least One Incidence of Treatment-Emergent Adverse Events (TEAEs) During the Study	19 Participants

PRIMARY outcome

Timeframe: From the Titration Period (investigational product is taken) to the End of Study Visit (up to 3.5 years)

Outcome measures

Outcome measures
Measure	Lacosamide (Safety Set) n=19 Participants Subjects randomized in this arm received lacosamide from 200 mg/day to 600 g/day, from the Titration to the End of Study Visit (up to 3.5 years).
Number of Subjects Who Withdraw Due to Adverse Events (AEs) During the Study	2 Participants

PRIMARY outcome

Timeframe: From the Titration Period (investigational product is taken) to the End of Study Visit (up to 3.5 years)

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Is a congenital anomaly or birth defect * Is as infection that requires treatment parenteral antibiotics * Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above

Outcome measures

Outcome measures
Measure	Lacosamide (Safety Set) n=19 Participants Subjects randomized in this arm received lacosamide from 200 mg/day to 600 g/day, from the Titration to the End of Study Visit (up to 3.5 years).
Number of Subjects With at Least One Incidence of Serious Adverse Events (SAEs) During the Study	2 Participants

SECONDARY outcome

Timeframe: From the beginning of the Monotherapy Period to the end of the Follow-Up Period (up to 3.1 years until the time of approval granted)

Population: The Full Analysis Set (FAS) consisted of subjects in the Safety Set (SS) who had at least 1 seizure diary assessment. Subjects who discontinued before the end date of 6 consecutive months were included in this analysis.

Subjects were considered seizure free if their seizure counts for every day over the entire Treatment Period was zero and if they completed the Treatment Period. A subject was considered seizure free, if no seizure occurred during the 6 consecutive months in the Evaluation Period. If one of the following occurred, the subject was not considered seizure free: * A documented seizure during 6 consecutive months of the Evaluation Analysis Period * Subject discontinued the study prematurely during the Evaluation Analysis Period * Missing Seizure Count Case Report Forms (CRFs) prior to completing the Evaluation Analysis Period

Outcome measures

Outcome measures
Measure	Lacosamide (Safety Set) n=13 Participants Subjects randomized in this arm received lacosamide from 200 mg/day to 600 g/day, from the Titration to the End of Study Visit (up to 3.5 years).
Number of Subjects Remaining Seizure Free for 6 Consecutive Months During the Monotherapy Period	6 Participants

SECONDARY outcome

Timeframe: From the beginning of the Monotherapy Period to the end of the Follow-Up Period (up to 3.1 years until the time of approval granted)

Population: The Full Analysis Set (FAS) consisted of subjects in the SS who had at least 1 seizure diary assessment. Subjects who discontinued before the end date of 12 consecutive months were included in this Analysis.

Subjects were considered seizure free if their seizure counts for every day over the entire Treatment Period was zero and if they completed the Treatment Period. A subject was considered seizure free, if no seizure occurred during the 12 consecutive months in the Evaluation Period. If one of the following occurred, the subject was not considered seizure free: * A documented seizure during 6 consecutive months of the Evaluation Analysis Period * Subject discontinued the study prematurely during the Evaluation Analysis Period * Missing Seizure Count Case Report Forms (CRFs) prior to completing the Evaluation Analysis Period. Subjects who discontinued before the end date of 6 consecutive months were included in this analysis.

Outcome measures

Outcome measures
Measure	Lacosamide (Safety Set) n=13 Participants Subjects randomized in this arm received lacosamide from 200 mg/day to 600 g/day, from the Titration to the End of Study Visit (up to 3.5 years).
Number of Subjects Remaining Seizure Free for 12 Consecutive Months During the Monotherapy Period	6 Participants

SECONDARY outcome

Timeframe: From the beginning of the Monotherapy Period to the end of the Follow-Up Period (up to 3.1 years until the time of approval granted)

Population: The Full Analysis Set (FAS) consisted of subjects in the Safety Set (SS) who had at least 1 seizure diary assessment. Subjects who discontinued before Monotherapy Period were not included in this Analysis.

For Time to discontinuation (event), Retention rate and 95% CI was calculated using the Kaplan-Meier method. Retention rate is indicated in Percent and 95% confidence intervals (CI) with respect to the Time to discontinuation.

Outcome measures

Outcome measures
Measure	Lacosamide (Safety Set) n=17 Participants Subjects randomized in this arm received lacosamide from 200 mg/day to 600 g/day, from the Titration to the End of Study Visit (up to 3.5 years).
Percentage of Participants in the Monotherapy Period Without Discontinuation Due to Adverse Events (AE) or Lack of Efficacy (LOE) Retention Rate after 6-months	81.3 Percentage of participant Interval 52.46 to 93.54
Percentage of Participants in the Monotherapy Period Without Discontinuation Due to Adverse Events (AE) or Lack of Efficacy (LOE) Retention Rate after 12-months	81.3 Percentage of participant Interval 52.46 to 93.54
Percentage of Participants in the Monotherapy Period Without Discontinuation Due to Adverse Events (AE) or Lack of Efficacy (LOE) Retention Rate after 18-months	81.3 Percentage of participant Interval 52.46 to 93.54
Percentage of Participants in the Monotherapy Period Without Discontinuation Due to Adverse Events (AE) or Lack of Efficacy (LOE) Retention Rate after 24-months	81.3 Percentage of participant Interval 52.46 to 93.54

SECONDARY outcome

Timeframe: From Titration Period up to Week 94

Population: Two Subjects withdrew during the AED Withdrawal Period (prior to the Evaluation Period).

Dose-normalized lacosamide Plasma Concentration (µg/mL) by Visit and Dose during the Evaluation Period.

Outcome measures

Outcome measures
Measure	Lacosamide (Safety Set) n=17 Participants Subjects randomized in this arm received lacosamide from 200 mg/day to 600 g/day, from the Titration to the End of Study Visit (up to 3.5 years).
Plasma Concentrations of Lacosamide Versus Time Postdose Concentration at First Visit	0.028 µg/mL Standard Deviation 0.016
Plasma Concentrations of Lacosamide Versus Time Postdose Concentration at Last Visit	0.034 µg/mL Standard Deviation 0.010

Adverse Events

Lacosamide

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lacosamide n=19 participants at risk Subjects randomized in this arm received lacosamide from 200 mg/day to 600 mg/day, from the Titration to the End of Study Visit (up to 3.5 years).
Nervous system disorders Convulsion	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Vascular disorders Varicose vein	5.3% 1/19 • Number of events 2 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years

Other adverse events

Other adverse events
Measure	Lacosamide n=19 participants at risk Subjects randomized in this arm received lacosamide from 200 mg/day to 600 mg/day, from the Titration to the End of Study Visit (up to 3.5 years).
Blood and lymphatic system disorders Leukopenia	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Ear and labyrinth disorders Vertigo	21.1% 4/19 • Number of events 5 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Eye disorders Dry eye	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Abdominal pain	10.5% 2/19 • Number of events 3 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Abdominal pain upper	10.5% 2/19 • Number of events 3 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Diarrhoea	10.5% 2/19 • Number of events 2 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Nausea	10.5% 2/19 • Number of events 2 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Aphthous stomatitis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Constipation	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Dry mouth	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Dyspepsia	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Gastritis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Gastrointestinal disorder	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Gastrointestinal disorders Paraesthesia oral	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
General disorders Chest pain	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
General disorders Irritability	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
General disorders Malaise	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
General disorders Pyrexia	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Hepatobiliary disorders Hepatic steatosis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Nasopharyngitis	36.8% 7/19 • Number of events 13 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Influenza	10.5% 2/19 • Number of events 2 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Acute tonsillitis	5.3% 1/19 • Number of events 2 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Bronchitis	6.2% 1/16 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Cystitis	5.3% 1/19 • Number of events 2 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Herpes virus infection	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Infected dermal cyst	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Laryngitis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Periodontitis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Pharyngitis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Infections and infestations Tinea pedis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Injury, poisoning and procedural complications Arthropod bite	10.5% 2/19 • Number of events 4 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Injury, poisoning and procedural complications Contusion	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Injury, poisoning and procedural complications Head injury	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Injury, poisoning and procedural complications Heat illness	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Injury, poisoning and procedural complications Injury	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Injury, poisoning and procedural complications Ligament sprain	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Injury, poisoning and procedural complications Tooth fracture	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Investigations Blood growth hormone increased	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Investigations Crystal urine present	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Investigations Gamma-glutamyltransferase increased	5.3% 1/19 • Number of events 2 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Investigations White blood cell count decreased	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Metabolism and nutrition disorders Decreased appetite	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Musculoskeletal and connective tissue disorders Back pain	5.3% 1/19 • Number of events 2 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Musculoskeletal and connective tissue disorders Pubic pain	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Musculoskeletal and connective tissue disorders Tenosynovitis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibrous histiocytoma	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Nervous system disorders Dizziness	52.6% 10/19 • Number of events 13 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Nervous system disorders Somnolence	42.1% 8/19 • Number of events 9 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Nervous system disorders Headache	15.8% 3/19 • Number of events 5 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Nervous system disorders Tremor	10.5% 2/19 • Number of events 2 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Nervous system disorders Cerebellar ataxia	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Nervous system disorders Complex partial seizures	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Nervous system disorders Hypoaesthesia	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Nervous system disorders Simple partial seizures	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Nervous system disorders Sudden onset of sleep	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Psychiatric disorders Depressed mood	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Psychiatric disorders Insomnia	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Reproductive system and breast disorders Uterine polyp	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Respiratory, thoracic and mediastinal disorders Vocal cord inflammation	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Skin and subcutaneous tissue disorders Eczema	15.8% 3/19 • Number of events 3 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Skin and subcutaneous tissue disorders Chloasma	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Skin and subcutaneous tissue disorders Dermatitis allergic	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Skin and subcutaneous tissue disorders Eczema asteatotic	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Skin and subcutaneous tissue disorders Pustular psoriasis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years
Skin and subcutaneous tissue disorders Urticaria	5.3% 1/19 • Number of events 1 • Adverse Events were collected from Visit 1 until Safety Follow-Up Visit (up to week 2 after last dose), for approximately 3.5 years

Additional Information

UCB

Cares

Phone: +1844599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60