NCT01921205

Study to Investigate Lacosamide as Add-on Therapy in Subjects ≥4 Years to <17 Years of Age With Partial Onset Seizures

Completed Phase 3 Results posted Last updated 18 July 2018

What this trial tests

Phase 3 trial testing Lacosamide in Epilepsy in 404 participants. Completed in 24 January 2017.

Timeline

29 August 2013

Primary endpoint
24 January 2017

24 January 2017

Quick facts

Lead sponsor	UCB Pharma
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	404
Start date	29 August 2013
Primary completion	24 January 2017
Estimated completion	24 January 2017
Sites	118 locations across Italy, Colombia, Taiwan, Poland, South Korea, Croatia, Russia, Belgium

Drugs / interventions tested

• Lacosamide (lacosamide) — full drug profile →
• Placebo

Conditions studied

• Epilepsy — all drugs for Epilepsy →

Sponsor

UCB Pharma — full company profile →

Who can join

Adults 4 to 16, any sex, with Epilepsy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Partial Onset Seizure (POS) Frequency Per 28 Days From Baseline to the Maintenance Period Primary · Baseline to Week 16 (or last value on treatment)

The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

Group	Value	95% CI
Placebo (FAS)	-1.55	-318.7 – 690.0
Lacosamide (FAS)	-3.05	-302.9 – 210.4

Proportion of Responders Where a Responder is Defined as a Participant With >= 50% Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period Secondary · Baseline to Week 16 (or last value on treatment)

Proportion of responders is presented as percentage of participants. A responder is a subject experiencing a 50 % or greater reduction in partial onset seizure frequency per 28 days from Baseline to the Maintenance Period.

Group	Value	95% CI
Placebo (FAS)	33.3
Lacosamide (FAS)	52.9

Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period Secondary · Baseline to Week 16 (or last value on treatment)

Proportion of subjects is presented as percentage of participants. A \>=25%-\<50% response in the Maintenance Period is defined as \>=25% to \<50% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A \>=50%-\<=75% response in the Maintenance Period is defined as \>=50% to \<=75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A 75% response in the Maintenance Period is defined as \>75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period.

>=25% - <50%

Group	Value	95% CI
Placebo (FAS)	14.7
Lacosamide (FAS)	11.8

>=50% - <=75%

Group	Value	95% CI
Placebo (FAS)	17.1
Lacosamide (FAS)	21.8

>75%

Group	Value	95% CI
Placebo (FAS)	15.9
Lacosamide (FAS)	31.2

Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) Secondary · Baseline to Week 16 (or last value on treatment)

The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

Group	Value	95% CI
Placebo (FAS)	-1.22	-250.6 – 477.0
Lacosamide (FAS)	-2.46	-219.2 – 210.4

Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) Secondary · Baseline to Week 16 (or last value on treatment)

Proportion of subjects is presented as percentage of participants. A \>=25%-\<50% response in the Treatment Period is defined as \>=25% to \<50% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A \>=50%-\<=75% response in the Treatment Period is defined as \>=50% to \<=75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A 75% response in the Treatment Period is defined as \>75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period.

>=25% - <50%

Group	Value	95% CI
Placebo (FAS)	15.3
Lacosamide (FAS)	16.5

>=50% - <=75%

Group	Value	95% CI
Placebo (FAS)	20.6
Lacosamide (FAS)	20.6

>75%

Group	Value	95% CI
Placebo (FAS)	8.8
Lacosamide (FAS)	23.5

Proportion of Subjects Experiencing no Change in Partial Onset Seizure Frequency (Between <25 % Reduction and <25 % Increase) Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) Secondary · Baseline to Week 16 (or last value on treatment)

Proportion of subjects is presented as percentage of participants. No change is defined as between \<25% reduction and \<25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise not between \<25% reduction and \<25% increase is defined as a change.

Group	Value	95% CI
Placebo (FAS)	32.0
Lacosamide (FAS)	20.6

Proportion of Subjects Experiencing an Increase in Partial Onset Seizure Frequency Per 28 Days of >=25 % From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) Secondary · Baseline to Week 16 (or last value on treatment)

Proportion of subjects is presented as percentage of participants. An increase is defined as a \>=25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise \<25% increase is defined as no increase.

Group	Value	95% CI
Placebo (FAS)	23.1
Lacosamide (FAS)	18.8

Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Simple Partial Seizures Secondary · Baseline to Week 16 (or last value on treatment)

The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

Group	Value	95% CI
Placebo (FAS)	-1.14	-250.6 – 477.0
Lacosamide (FAS)	-1.25	-217.4 – 100.2

Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Complex Partial Seizures Secondary · Baseline to Week 16 (or last value on treatment)

The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

Group	Value	95% CI
Placebo (FAS)	-0.98	-78.0 – 239.7
Lacosamide (FAS)	-2.06	-131.8 – 210.4

Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Secondary Generalized Seizures Secondary · Baseline to Week 16 (or last value on treatment)

The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

Group	Value	95% CI
Placebo (FAS)	-1.0	-204.7 – 39.8
Lacosamide (FAS)	-2.81	-99.3 – 72.7

Proportion of Seizure Free Days During the Maintenance Period for Subjects Who Completed the Maintenance Period Secondary · Week 7 to Week 16

The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded.

Group	Value	95% CI
Placebo (FAS)	0.65	± 0.35
Lacosamide (FAS)	0.71	± 0.32

Proportion of Subjects Who Achieved "Seizure Free" Status (Yes/no) for Subjects Who Completed the Maintenance Period Secondary · Week 7 to Week 16

The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded.

Group	Value	95% CI
Placebo (FAS)	9.7
Lacosamide (FAS)	15.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from Visit 1 until Safety Follow-Up Visit up to week 24.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 13/172 (8%)

Deaths: 0/172

Lacosamide

Serious: 11/171 (6%)

Deaths: 0/171

Serious adverse events (23 terms)

Reaction	System	Placebo	Lacosamide
Convulsion	Nervous system disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Pneumonia	Infections and infestations	—	—
Bradycardia	Cardiac disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Gastrointestinal inflammation	Gastrointestinal disorders	—	—
Hepatitis	Hepatobiliary disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Bronchitis	Infections and infestations	—	—
Bronchopneumonia	Infections and infestations	—	—
Dengue fever	Infections and infestations	—	—
Gastroenteritis	Infections and infestations	—	—
Respiratory tract infection	Infections and infestations	—	—
Tonsillitis	Infections and infestations	—	—
Postoperative respiratory distress	Injury, poisoning and procedural complications	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Dystonia	Nervous system disorders	—	—
Partial seizures	Nervous system disorders	—	—
Syncope	Nervous system disorders	—	—
Emotional disorder of childhood	Psychiatric disorders	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Placebo	Lacosamide
Somnolence	Nervous system disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Dizziness	Nervous system disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Headache	Nervous system disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Pharyngitis	Infections and infestations	—	—
Diarrhoea	Gastrointestinal disorders	—	—

Most-reported serious reactions: Convulsion, Abdominal pain, Pneumonia, Bradycardia, Vomiting, Constipation, Gastrointestinal inflammation, Hepatitis.

Data from ClinicalTrials.gov NCT01921205 adverse events section.

Sponsor's own description

Study to evaluate the efficacy of Lacosamide (LCM) administered in addition to 1 to ≤3 other Anti-Epileptic Drugs in subjects with epilepsy ≥4 years to \<17 years of age who currently have uncontrolled partial onset seizures.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy and tolerability of adjunctive lacosamide in pediatric patients with focal seizures.
   Farkas V, Steinborn B, Flamini JR, Zhang Y, et al · · 2019 · cited 48× · PMID 31462582 · DOI 10.1212/wnl.0000000000008126
2. Analyses of seizure responses supportive of a novel trial design to assess efficacy of antiepileptic drugs in infants and young children with epilepsy: Post hoc analyses of pediatric levetiracetam and lacosamide trials.
   Johnson ME, McClung C, Bozorg AM. · · 2021 · cited 11× · PMID 34033237 · DOI 10.1002/epi4.12482
3. Lacosamide add-on therapy for focal epilepsy.
   Babar RK, Bresnahan R, Gillespie CS, Michael BD. · · 2021 · cited 10× · PMID 33998660 · DOI 10.1002/14651858.cd008841.pub3
4. Efficacy and tolerability of adjunctive lacosamide in patients aged <4 years with focal seizures.
   Makedonska I, Ng YT, Beller C, Bozorg A, et al · · 2024 · cited 6× · PMID 38375995 · DOI 10.1002/acn3.52004
5. Pitfalls of using video-EEG for a trial endpoint in children aged <4 years with focal seizures.
   Bozorg A, Beller C, Jensen L, Arzimanoglou A, et al · · 2024 · cited 2× · PMID 38318689 · DOI 10.1002/acn3.51999
6. Questionable Industry-Sponsored Postneonatal Pediatric Studies in Slovenia.
   Rose K, Neubauer D, Grant-Kels JM. · · 2019 · cited 2× · PMID 31388360 · DOI 10.1016/j.curtheres.2019.01.002
7. Long-term efficacy, safety, and tolerability, including behavior and executive functioning, during adjunctive lacosamide treatment in pediatric patients with uncontrolled epilepsy.
   Farkas MK, Makedonska I, Beller C, Bourikas D, et al · · 2024 · PMID 39216464 · DOI 10.1016/j.yebeh.2024.109989